Problem Solving in

Neuroradiology
Meng Law, MD, MBBS, FRACR
Professor of Radiology and Neurological Surgery
Director of Neuroradiology
Keck School of Medicine
University of Southern California
Los Angeles, California

Peter M. Som, MD, FACR

Professor of Radiology, Otolaryngology, and Radiation Oncology
Department of Radiology
Mount Sinai School of Medicine
New York, New York

Thomas P. Naidich, MD, FACR

Professor of Radiology and Neurosurgery
Mount Sinai School of Medicine
New York, New York
1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA19103-2899

PROBLEM SOLVING IN NEURORADIOLOGY ISBN: 978-0-323-05929-9

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 To my parents, Lawrence and Sue, for their love and inspiration
ML

To my wife, Judy, for her support and love

PMS

To my dear wife, Michele Levin Naidich, whose love balances my life

TPN
Contributors
Manzoor Ahmed, MBBS, MD Julia Frühwald-Pallamar
Assistant Professor of Radiology Department of Radiology
Lerner College of Medicine Medical University of Vienna
Imaging Institute Vienna General Hospital
Cleveland Clinic, Ohio Vienna, Austria
Neurodegenerative Disorders Infection/Inflammation

Pascal Bou-Haidar, BMed, MEngSc, FRANZCR Andre D. Furtado, MD

Mount Sinai Hospital Clinical Fellow
New York, New York Department of Radiology
Advanced MR (MR Spectroscopy, Diffusion Imaging, Children’s Hospital of Pittsburgh Medical Center
Diffusion Tensor Imaging, and Perfusion Imaging): Pittsburgh, Pennsylvania
A Multiparametric Algorithmic Approach to Problem Intrauterine and Perinatal Infections
Solving in Neuroradiology Neuroimaging of Pediatric Hypoxic–Ischemic Injury
Epilepsy
Rajiv Gupta, MD, PhD
Alessandro Cianfoni, MD Director, Ultra-High Resolution Volume CT Lab
Assistant Professor of Neuroradiology Department of Radiology
Radiology Department Massachusetts General Hospital
Medical University of South Carolina Boston, Massachusetts
Charleston, South Carolina Multidetector Computed Tomography as a Problem-Solving
Brain Trauma Tool in Neuroradiology
Imaging of Spine Trauma
Sofia S. Haque, MD
Cesare Colosimo, MD Clinical Assistant Professor of Radiology
Professor of Radiology New York Presbyterian Hospital
Director of Radiology Weill Cornell ­Medical Center;
Department of Bioimages and Radiological Sciences Memorial Sloan-Kettering Cancer Center
Policlinico “A. Gemelli” New York, New York
Catholic University of Rome Metabolic Disorders
Rome, Italy
Brain Trauma Jane J. Kim, MD
Imaging of Spine Trauma Assistant Professor of Clinical Radiology
University of California, San Francisco
Marco Essig, MD, PhD San Francisco, California
Professor of Radiology Magnetic Resonance Imaging as a Problem-Solving Tool
Heidelberg Medical School;
Department of Neuroradiology Paul E. Kim, MD
University of Erlangen Assistant Professor of Radiology
Erlangen, Germany Director of Spine Imaging and Intervention
Tumor Keck School of Medicine
University of Southern California
Girish M. Fatterpekar, MD Los Angeles, California
Assistant Professor, Radiology Spine and Lower Back Pain
Section Neuroradiology Spine: Tumors and Infection
New York University School of Medicine
New York, New York
Head and Neck Radiology

vii
viii Contributors

Lale Kostakoglu, MD, MPH Sunithi Mani

Professor of Radiology Assistant Professor
Director, PET/CT Oncology and Research Department of Radiodiagnosis
Department of Radiology Christian Medical College
Division of Nuclear Medicine Vellore, India
Mount Sinai School of Medicine Multidetector Computed Tomography as a Problem-Solving
New York, New York Tool in Neuroradiology
PET/CT Imaging in Squamous Cell Carcinoma of the Head
and Neck Stephan Meckel, MD
Consultant Neuroradiologist
Saulo Lacerda, MD Department of Neuroradiology
MedImagem-Hospital Beneficencia Portuguesa Neurocenter
Sao Paulo, Brazil University Hospital Freiburg
Advanced MR (MR Spectroscopy, Diffusion Freiburg, Germany
Imaging, Diffusion Tensor Imaging, and Perfusion Diagnostic Angiography
Imaging): A Multiparametric Algorithmic Approach
to Problem Solving in Neuroradiology Amit Mehndiratta, MBBS, MMST, DPhil
Epilepsy Institute of Biomedical Engineering
Intrauterine and Perinatal Infections University of Oxford
Neuroimaging of Pediatric Hypoxic–Ischemic Injury Oxford, United Kingdom
Multidetector Computed Tomography as a Problem-Solving
Meng Law, MD, MBBS, FRACR Tool in Neuroradiology
Professor of Radiology and Neurological Surgery
Director of Neuroradiology Pratik Mukherjee, MD, PhD
Keck School of Medicine Associate Professor of Radiology and Biomedical
University of Southern California Imaging, Bioengineering, and Therapeutic Sciences
Los Angeles, California Department of Radiology and Biomedical Imaging
Advanced MR (MR Spectroscopy, Diffusion Imaging, ­ University of California, San Francisco
Diffusion Tensor Imaging, and Perfusion Imaging): San Francisco, California
A Multiparametric Algorithmic Approach to Problem Magnetic Resonance Imaging as a Problem-Solving Tool
Solving in Neuroradiology
Epilepsy Thomas P. Naidich, MD, FACR
Professor of Radiology and Neurosurgery
Michael Lev, MD, FAHA Mount Sinai School of Medicine
Director, Emergency Neuroradiology New York, New York
and Neurovascular Lab Intrauterine and Perinatal Infections
Massachusetts General Hospital Neuroimaging of Pediatric Hypoxic–Ischemic Injury
Associate Professor of Radiology
Harvard Medical School Danielle Nanigian, MD
Boston, Massachusetts University of California at San Diego
Multidetector Computed Tomography as a Problem- Coronado, California
Solving Tool in Neuroradiology Spine Procedures: Biopsies

John K. Lyo, MD Darren B. Orbach, MD, PhD

Assistant Professor of Radiology Assistant Professor of Radiology
New York Presbyterian Hospital Harvard Medical School;
Weill Cornell Medical Center; Director of Interventional and Neurointerventional
Memorial Sloan-Kettering Cancer Center Radiology
New York, New York Children’s Hospital Boston
Metabolic Disorders Boston, Massachusetts
Neurointerventional Radiology
 Contributors ix

Michael Phillips, MD Majda M. Thurnher, MD

Vice Chairman, Research and Academic Affairs Associate Professor of Radiology
Imaging Institute Department of Radiology
Cleveland Clinic Foundation Medical University of Vienna
Cleveland, Ohio Vienna General Hospital
Neurodegenerative Disorders Vienna, Austria
Infection/Inflammation
Stuart Pomerantz, MD
Department of Radiology Johan W.M. Van Goethem, MD, PhD
Massachusetts General Hospital Vice-Head of Neuroradiology
Boston, Massachusetts Staff Member
Multidetector Computed Tomography as a Problem-Solving University of Antwerp
Tool in Neuroradiology Antwerp, Belgium
Spine and Lower Back Pain
Stefan B. Puchner, MD Spine: Tumors and Infection
Medical University of Vienna
Department of Radiology Alyssa T. Watanabe, MD
University Hospital Vienna Clinical Associate Professor in Radiology
Vienna, Austria University of Southern California
Infection/Inflammation School of Medicine
Los Angeles, California
Ajit Puri, MD Spine and Lower Back Pain
Clinical Fellow Spine: Tumors and Infection
Interventional Neuroradiology/Endovascular
­Neurosurgery Stephan G. Wetzel, MD
Department of Radiology/Neurosurgery Department of Neuroradiology
Brigham and Women’s Hospital Swiss Neuro Institute
Boston, Massachusetts Klinik Hirslanden Zürich
Neurointerventional Radiology Zürich, Switzerland
Diagnostic Angiography
Andrea Rossi, MD
Head, Department of Pediatric Neuroradiology Wade Wong, DO
G. Gaslini Children’s Hospital; University of California at San Diego
Contract Professor of Neuroradiology Coronado, California
University of Genoa Spine Procedures: Biopsies
Genoa, Italy
Imaging of Congenital Brain Abnormalities Robert J. Young, MD
Assistant Professor of Radiology
Peter M. Som, MD, FACR New York Presbyterian Hospital
Professor of Radiology, Otolaryngology, Weill Cornell Medical Center;
and Radiation Oncology Memorial Sloan-Kettering Cancer Center
Department of Radiology New York, New York
Mount Sinai School of Medicine Metabolic Disorders
New York, New York
Head and Neck Radiology

Ruth Thiex, MD, PhD

Departments of Neurosurgery and Radiology
Brigham and Women’s Hospital
Harvard Medical School
Boston, Massachusetts
Neurointerventional Radiology
Foreword
In a departure from commonly constructed textbooks attending physician. Who better than Tom Naidich to
in radiology, three eminent leaders in the field of lead us through the intricacies of brain anatomy and
­neuroradiology—Drs. Law, Som, and Naidich—have to show us how important this knowledge is when
approached imaging in an original and highly educa- applying advanced imaging protocols, or Peter Som
tional manner. With separate sections (each with indi- to take the reader through the basics of head and neck
vidual chapters) on advanced imaging, interventional imaging and address questions of a critical nature
procedures, specific diagnosis, and anatomic consider- related to ENT radiology, or Meng Law to demonstrate
ations, these authors, along with those who have co- the current state-of-the-art of neuroimaging. For years
authored chapters, bring their material to life with the I have learned from them, and to this day I marvel at
Socratic method, posing critical questions throughout their command of the intricacies of neuroimaging.
the book and then answering them. Congratulations to Drs. Law, Som, and Naidich, not
There are none more qualified than these three pri- only for conceiving this new way of presenting diagnos-
mary authors to guide us through the many areas of tic imaging but also for offering to the neuroradiology
neuroimaging. Their deep knowledge of the field and and neuroscience community a book that will provide
their love of teaching—imparting knowledge, combined new insights into diagnosis and intervention in neuro-
with a firm foundation of the underlying anatomy of logical diseases.
the brain, head and neck, and spine and the associ-
ated imaging techniques—results in a textbook that Robert M. Quencer, MD
will appeal to all levels of radiologists, from trainee to

xi
Preface
Neuroradiology is a subspecialty field that has seen i­ nterventional procedures. The third and largest sec-
exciting advances over the past few decades. The advent tion approaches problem solving in neuroradiology in a
of MRI in the 1980s began an era of new techniques disease-based fashion, covering brain and spine neuro-
for studying the central nervous system. Neurological radiologic pathology. The fourth section was developed
disorders are often complex, and to make a diagnosis to approach diseases in different anatomic regions, in
requires knowledge of neuroanatomy, neuropathology, particular spinal as well as head and neck disorders.
and neurophysiology, as well as knowledge of the tools We recognize that to provide a comprehensive text-
enabling us to image these entities. As a result, we hope book in neuroradiology would be a challenge. So rather
to provide a textbook that describes how to resolve than covering every aspect of neuroradiology, this text-
many of the diagnostic problems facing the clinician book serves as a practical approach toward problem
and diagnostician in a systematic fashion. solving. Our hope is that this will serve as a reference
We approached this textbook by dividing it into textbook that will benefit a spectrum of readers, from
four distinct sections, based in part on the expertise of medical students, radiology residents, and neuroradiol-
the editors. The first section provides a state-of-the-art ogy fellows, to the seasoned neuroradiologist. Residents
review of advanced imaging modalities available for studying for the radiology board certification and fel-
problem solving, which can help increase the sensitiv- lows preparing for the certificate of added qualification
ity and specificity of neurodiagnosis. In this section we (CAQ) examinations will find the combination of gen-
review multidetector CT, conventional MRI, advanced eral knowledge and case-based sections to be valuable
MRI (including MR spectroscopy, perfusion, and dif- in a problem-solving approach. It may also be of benefit
fusion), and nuclear medicine, in particular positron for students, residents, and practitioners in neurology,
emission tomography, as problem-solving tools. neurologic surgery, and the neurosciences.
The second section addresses some of the proce-
dures performed in neuroradiology, including diag- Meng Law, MD, MBBS, FRACR
nostic ­angiography, interventional neuroradiology Peter M. Som, MD
or endovascular neurosurgery, and, of course, spine Thomas P. Naidich, MD

Acknowledgments
I would like to acknowledge the invaluable assistance of my secretary, Ms. Elba Colman, for enabling me to complete
this work.
TPN

xiii
Acknowledgments
I would like to acknowledge the invaluable assistance of my secretary, Ms. Elba Colman, for enabling me to complete
this work.

TPN
 chapter 1

Multidetector Computed
Tomography as a Problem-
Solving Tool in Neuroradiology
Rajiv Gupta, Sunithi Mani, Amit Mehndiratta, Stuart Pomerantz,
and Michael Lev

INTRODUCTION
is the main diagnostic tool for both of these conditions.
The concept of x-ray computed tomography (CT) was The salient features, protocols, and pitfalls in the use of
pioneered by Sir Godfrey Hounsfield at EMI Central MDCT for a variety of conditions encountered in the
Research Laboratories (Middlesex, United Kingdom) emergency department are summarized here.
and concurrently by Allan McLeod Cormack at Tufts
University (Boston, MA, USA). Their main idea of using
Fractures
multiple projections to create tomographic images
formed the basis of the EMI scanner, the first clinical CT is excellent for showing bony anatomy and far
brain scanner. Since the days of the first brain scan in the exceeds the capabilities of MRI. With the advent of fast
early 1970s, CT has come a long way. Multidetector com- scanning and multiplanar reconstructions, it now is
puted tomography (MDCT) has seen a steady increase in feasible to demonstrate various types of skull fractures
the capabilities, availability, and dedicated protocols for in exquisite detail. For example, the various types of Le
neurologic applications. Although magnetic resonance Fort fractures now can be depicted quickly and easily.
imaging (MRI) clearly plays an important role in neu- Three-dimensional (3-D) renderings of these different
roradiology, CT is the main workhorse. Table 1-1 lists a fractures are invaluable to ear, nose, and throat (ENT)
compilation of the main advantages and disadvantages and plastic surgeons for rendering appropriate therapy.
of MDCT and MRI in neurologic applications. Because of their low sensitivity, skull radiographs have
This chapter illustrates how the excellent technical been supplanted by CT, which now is a part of emer-
capabilities of a modern MDCT scanner can be put to gency workup in nearly all trauma centers.
use for problem solving in neuroradiology. The expo- The optimal protocol for detecting calvarial and max-
sition is example driven. The requirements for the CT illofacial fractures requires thin axial slices constructed
protocols for each application domain are summarized using a sharp kernel (e.g., bone kernel for a GE scan-
and illustrated with the help of clinical examples. Many ner or H50 sharp kernel for a Siemens scanner). The
clinical pearls and pitfalls are presented and illustrated. axial slices must be at least 1.25 mm thick with about
Guidelines for image acquisition and interpretation are 50% overlap. These scans may be augmented by coro-
discussed. nal, sagittal, multiplanar oblique, or 3-D views to aid in
visualization. The reviewing radiologist requires multi-
MDCT IN THE EMERGENCY planar reconstructions to assess bony asymmetries and
DEPARTMENT alignment as well as certain structures that are optimally
visualized in the coronal or sagittal imaging planes. The
After a patient has been stabilized in the emergency referring physicians require 3-D reconstructions for pre-
department, imaging is directed at providing a clearer operative planning and intraoperative guidance. Figure
picture of the extent of injury and information about 1-1 shows selected images from the case of a 45-year-old
potential treatments. The ability of CT to rapidly image man who presented after a fall from a 30-foot ladder.
traumatic conditions has made it invaluable in acute The axial CT slices show fractures of the frontal emi-
neurotrauma management. CT is the vital imaging nence and parietal bone. However, the interrelationship
modality for determining the full extent and effects of between the fracture fragments is much better appreci-
the brain injury. Lesions commonly seen on CT include ated on the 3-D surface-rendered views, which show
calvarial fractures, acute intraaxial and extraaxial hem- the extent of fracture from frontal eminence to parietal
orrhage, hemorrhagic contusions, diffuse axonal injury, bone. Use of 3-D views is not limited to trauma cases.
and spinal fractures. Figure 1.2 shows the similar application of the 3-D sur-
For emergent management, the lesions can be face-rendering technique to visualize a congenital cra-
broadly classified as traumatic or nontraumatic. MDCT nial malformation.

3
4 Section I  Advanced Modalities: Protocols and Optimization

Table 1-1 C
 omparison of MDCT and MRI for individualized checklist of frequent misses, such as frac-
­Neurologic Applications tures of the condylar head, zygoma, around the foramen
MDCT MRI magnum, pterygoid plates (Le Fort fractures), and nasal
bones.
Fast, more available Slower, less available Figure 1-5 shows the case of an 18-year-old man with
Few contraindications Multiple contraindications a history of impaling his face onto the branch of a tree
who presented with facial paresthesias. CT scan images
Radiation exposure No radiation exposure
show a hypodense foreign body adjacent to the infra-
Good for acute hemorrhage Excellent for phases of orbital nerve that extends into the anterior wall of the
hemorrhage left maxillary sinus. Subcutaneous emphysema is pres-
Excellent for bone and Poor visualization of bone, ent along the entrance track adjacent to the infraorbital
air–tissue interfaces air–tissue interfaces foramen. The sagittal and coronal images also demon-
Poor soft tissue contrast Great for soft tissues strate the foreign body and mucosal thickening in the
left maxillary sinus.
Higher chance of contrast ­ Lower chance of contrast
reaction reaction
Figure 1-6 shows a common pitfall in CT scans
of traumatic injury. A CT scan was performed on a
Nephrotoxic contrast Nephrotoxic contrast (NSF) 54-year-old man who fell from a tree and complained
Can only measure attenuation Sensitive to different tissue of irritation in the left eye. Axial CT scan demonstrated
properties proptosis of the left globe with air in the extraconal
Excellent contrast-enhanced Good contrast-enhanced post-septal region, along the lateral aspect of the orbit,
angiograms angiograms extending posteriorly up to the orbital apex. This was
presumed to be posttraumatic air, likely secondary
Need contrast for computed Noncontrast magnetic
tomographic angiography ­resonance angiography to a fracture. However, a fracture was not identified.
(based on flow) The patient returned 2 months later, when MRI scan
showed persistent proptosis and extensive inflamma-
MDCT, Multidetector computed tomography; MRI, magnetic resonance
­imaging; NSF, nephrogenic systemic fibrosis.
tory and phlegmonous changes with enhancement. The
central nonenhancing portion was thought to be the
necrotic core of an abscess. The patient was emergently
taken to the operating room, where a 2-cm wood chip
The most common pitfall in evaluating calvarial and was removed from the left orbit. The take-home point
skull base fractures is improper protocol. Evaluation is that wood can have a variety of appearances on CT,
of the bony anatomy on slices that are too thick or do with dry wood essentially resembling air in Hounsfield
not use a sharp kernel can be detrimental. Figure 1-3, units (HU).
which shows thin slices reconstructed using a sharp ker-
nel, demonstrates a subtle right occipital fracture that
Intracranial Hemorrhage
extends into the skull base. This fracture was missed on
the slices acquired at 2.5-mm thickness and standard Hemorrhage due to a direct mechanism, either penetrat-
kernel. Due to the subgaleal hematoma in the vicinity ing or blunt, may be extraaxial (epidural or subdural),
and a high clinical suspicion, retrospective reconstruc- intraparenchymal, or associated with a brain contusion.
tions at 1.25-mm slice thickness using a sharp kernel All of these pathologies, with varying degrees of sensi-
demonstrated the nondisplaced fracture shown in the tivity and specificity, can be detected and characterized
figure. using MDCT. Rotational forces can lead to hemorrhagic
The scenario described exemplifies a separate but shear and diffuse axonal injury at characteristic loca-
related feature of MDCT. When the projection data tions such as the corpus callosum and gray–white junc-
are acquired using a helical or spiral protocol, thinner tion. CT has relatively low sensitivity for diffuse axonal
image slices can be retrospectively reconstructed at any injury, which is apparent on only 20% to 50% of initial
user-defined spacing and overlap. This can be done as CT scans. Diffuse axonal injury lesions that are visible
long as the raw projection data are available. Therefore, are commonly found in the subcortical white matter,
operationally it is mandatory for the raw projection data centrum semiovale, corpus callosum, basal ganglia,
to be saved, at least for a few days after the scanning, brainstem, and cerebellum.
while the clinical questions during acute care are still The volume inside the calvaria is limited and fixed.
being addressed. This volume is composed of three components: cerebro-
Even though tomographic slices are more sensitive spinal fluid, blood, and brain tissue. According to the
in detecting fractures, scout views sometimes can show Monro-Kellie hypothesis, intracranial pressure remains
linear fractures that may be missed on the tomographic stable as long as the volume added to any one of these
data (Figure 1-4). It is a good practice to always examine components is balanced by the volume displaced.
the scout view with all CT data. It also is a good practice Therefore, a sudden rise in the amount of any one of
to review sagittal and coronal views, which can be eas- these components may cause the intracranial pressure
ily reconstructed on the scanner console. Coronal views to increase if the volume of the other two components
are especially helpful because they are more forgiving of remains constant. The greatest risk to a patient with any
side-to-side misregistration, allowing easier comparison traumatic injury is a fast-growing intracranial hema-
between the left and right sides. It is useful to have an toma leading to increased intracranial pressure and
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 5

SECTION I
A

B
Figure 1-1 Noncontrast maxillofacial multidetector computed tomography of a 45-year-old man who presented with a history of a fall from a
30-foot ladder. A: Axial computed tomographic slices showing fracture through the frontal eminence and parietal bone. B: The extent of fracture
from the frontal eminence to the left parietal bone and the relationship between the various fracture fragments are much better appreciated on
these three-dimensional surface-rendered views.

A B
Figure 1-2 Congenital craniofacial malformations are better demonstrated using three-dimensional (3-D) surface-rendered views than routine
axial views. Axial (A) and 3-D surfaced-rendered (B) views of plagiocephaly in a neonatal patient.
6 Section I  Advanced Modalities: Protocols and Optimization

Figure 1-3 Subtle, nondisplaced fracture of the right occipital bone that was not visible on thicker slices. Adjacent subgaleal hematoma overly-
ing the fracture is better seen on the soft tissue windows.

Figure 1-4 Left parietal fracture that is more easily visualized on the scout view.
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 7

herniation. The occurrence of this potentially fatal com- a result of venous bleed. Subarachnoid hemorrhage is

SECTION I
plication is not apparent until clinical deterioration has most commonly caused by aneurysmal bleed but also
started and recovery already is endangered. may be posttraumatic.
Intraaxial hematoma may stop because of the tam- MDCT is an ideal modality for evaluating intracranial
ponade effect from the surrounding brain parenchyma, hemorrhage. On a noncontrast CT scan, which is both
or it may grow in size over time. It may cause midline quite sensitive and specific in detecting hemorrhage,
shift, herniation, or ventricular entrapment, or it may acute blood products appear hyperdense compared with
cross into an adjacent compartment (i.e., become a sub- normal brain parenchyma. If intracranial ­hemorrhage is
arachnoid or intraventricular hemorrhage). in the differential, a noncontrast CT scan must be per-
Extraaxial hematoma may be due to an arterial or formed before contrast is given. Coronal images have
a venous bleed. Typically, epidural hematomas result been shown to improve the sensitivity and specificity of
from arterial bleeds because arterial pressure is required detection.
for the blood to dissect between the outer layer of the In the emergency department setting, it is impor-
dura and the skull. Classically, it presents as a convex tant to be aware of many pitfalls in the detection of
hyperdense collection that stops at the sutures. A sub- acute intracranial hemorrhage. First, close attention
dural blood collection in the hemorrhage is generally must be paid to the window-level setting for viewing
the images because a subtle hematoma may be missed
if an improper window-level setting is used (Figure
1-7). An acute subdural hematoma (SDH) that is less
than 72 hours old appears hyperdense compared to
brain parenchyma on a CT scan. As the blood products
evolve, they progressively become hypodense. A sub-
acute SDH (3 days to 3 weeks old) may appear either
isodense or hypodense, whereas a chronic SDH that is
more than 3 weeks old is generally always hypodense.
An isodense SDH may blend in with the adjacent brain
parenchyma, making detection difficult, especially
when it is bilateral (Figure 1-8). Medial displacement
A of the gray–white matter interface and verification that
the sulci extend up to the inner table of the calvaria are
important radiologic findings when an isodense SDH
is present.
Acute ongoing bleeding imparts a complex appear-
ance to otherwise subacute or chronic hemorrhage.
Because the morbidity and mortality associated with
spontaneous intracerebral hemorrhage are correlated
with hematoma progression, early radiologic signs that
predict hematoma expansion have been a subject of
active research. Patients who present very early to the
hospital and those who are taking anticoagulation med-
ications are likely to show hematoma expansion after
presentation to the emergency department. Presence
of gadolinium-based contrast agent in the hematoma
B during MRI scanning has been associated with later
­hematoma expansion. A similar sign for CT scanning
has been identified; extravasation of CT contrast agent
into the hematoma has been shown to predict hema-
toma expansion.
Goldstein and colleagues showed that contrast
extravasation within the hematoma on computed tomo-
graphic angiography (CTA) represents ongoing bleed-
ing. Therefore, this so-called spot sign identifies patients
who are at high risk for subsequent hematoma expan-
sion (Figure 1-9) and thus can be used to select patients
who are most likely to benefit from interventions aimed
C at arresting ongoing bleeding. Spot sign, which has a
very high negative predictive value, was independently
Figure 1-5 Patient with facial paresthesias after being impaled by confirmed by Wada and colleagues, who showed that
a tree branch. Triplanar computed tomographic images at the level of the presence of tiny enhancing foci in the hematoma
the infraorbital foramen show a foreign body adjacent to the infra-
orbital nerve. A: Axial slice showing the foreign body in the anterior after administration of contrast is associated with hema-
wall of the left maxillary sinus. B, C: Full extent of the foreign body in toma expansion. They found the sensitivity, specificity,
sagittal and coronal sections respectively. positive predictive value, negative predictive value, and
8 Section I  Advanced Modalities: Protocols and Optimization

A B

C D
Figure 1-6 Multidetector computed tomography in a patient with pain in the left eye after a fall from a tree. A: Axial slice showing a focus of
low density lateral to the left lateral rectus muscle that was assumed to be posttraumatic air. B, C: Axial postcontrast magnetic resonance images
acquired 2 months later showing persistent proptosis, inflammatory changes, and enhancement in the same region with central nonenhancing
component. D: A 2-cm piece of wood that was removed from the left orbit. (Images courtesy Drs. Huey-Jen Lee, University of Medicine and Den-
tistry, New Jersey (UMDNJ), and Michelle Rotblat, Massachusetts General Hospital (MGH), Boston.)

Figure 1-7 Subtle sub-

dural hematoma after trau-
matic injury, axial brain
section view at L = 30 HU,
W = 100 HU (A) and L = 80
HU, W = 200 HU (B). Note
the importance of proper
window-level setting for
visualization of a small right
temporoparietal subdural A B
hematoma.
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 9

SECTION I
A B C
Figure 1-8 Axial brain scans showing isodense subdural hematoma that may be hard to detect because it blends in with brain parenchyma.

likelihood ratio of this finding for expansion were 91%, ­ rimarily hypertensive. The overall mortality was close
p
89%, 77%, 96%, and 8.5, respectively. to 15%, with no mortality attributable to lacunar
Noncontrast CT is quite sensitive for detecting sub- infarcts.
arachnoid hemorrhage. If a subarachnoid hemorrhage CT scanning plays a pivotal role in the management
is detected, contrast-enhanced CTA should be per- of acute stroke and is the first-line imaging modality
formed next to rule out an aneurysm. Modern scanners when a patient suspected of having acute stroke arrives
cover the entire head in less than 15 seconds after con- in the emergency department. A combination of non-
trast administration. The delay between the start of con- contrast CT and CTA provides a quick and noninvasive
trast injection and the start of image acquisition can be method for ruling out hemorrhage, detecting regional
varied to image either the arterial or the venous phase ischemia, and demonstrating the site of vascular occlu-
of opacification. Therefore, vascular pathologies, such sion. In addition, CT perfusion imaging, currently a
as aneurysm, arteriovenous malformation (AVM), dural subject of intense research, has the potential for deter-
arteriovenous fistula, cavernous carotid fistula, and mining not only the tissue that has progressed to infarc-
venous sinus thrombosis, can be detected. Although tion but also the tissue in the ischemic penumbra that
conventional catheter angiography remains the gold is at risk. Major advances in neuroprotective therapeutic
standard for aneurysm imaging, CT has replaced it as regimens in conjunction with such advanced imaging
the first-line modality. The sensitivity of CTA in detect- have the potential to limit the ischemic damage beyond
ing small aneurysms is only marginally inferior to that the core of the infarct.
of conventional angiography. For example, it can clearly Figure 1-11 shows a typical sequence of imaging
depict any partial thrombosis of the aneurysm, size of examinations that are undertaken at a specialized stroke
the neck, neck-to-dome ratio, small vessels near the center to manage acute stroke. The sequence is discussed
base of the aneurysm, and any vessels arising from the in the following subsections.
aneurysm sac (Figure 1-10). In most situations, CTA
provides sufficient information that will guide the staff Non–Contrast-Enhanced CT
in making the decision to take the patient directly to
the operating room, thus obviating the need for inva- A noncontrast CT scan is the first-line imaging study in
sive angiography. patients suspected of having acute stroke. This simple,
noninvasive examination reveals a wealth of infor-
MDCT IN MANAGEMENT mation that is available immediately and has a direct
impact on clinical management. It quickly helps in
OF ACUTE STROKE
determining if the signs and symptoms being observed
Acute stroke is a clinical syndrome. Approximately can be attributed to intracranial hemorrhage (i.e., hem-
15% of acute strokes are hemorrhagic; the remaining orrhagic stroke), hydrocephalus, or a mass lesion. If any
85% are ischemic. A tally of acute stroke presenta- of these conditions is determined to be the case, non-
tions at our institution from 1999 to 2005 revealed contrast CT may be followed by CTA or MRI for further
that approximately 30% of ischemic strokes were car- evaluation. In most instances, an acute stroke is quite
dioembolic, 30% from large vessels, 20% from small apparent from the clinical presentation. The biggest
vessels/lacunar, and 20% from other or unknown contribution of noncontrast CT is ruling out intracra-
etiologies. The majority of hemorrhagic strokes were nial hemorrhage so that appropriately selected patients
10 Section I  Advanced Modalities: Protocols and Optimization

A B

C D
Figure 1-9 Hematoma at presentation (A) and 1 day later (B) showing interval growth of hematoma. Computed tomographic scan (C) after
contrast has been administered for acquisition of an angiogram (D). Active extravasation of contrast into the hematoma can be readily appreci-
ated in C and D. This so-called spot sign correlates with hematoma expansion.

can be started on intravenous (IV) tissue plasminogen Mountain View, CA) is gaining popularity at some cen-
activator (tPA) therapy. For this reason, noncontrast CT ters for patients who do not meet the time window for
is part of the guidelines for management of acute stroke. IV tPA.
The current imaging standard of care in acute stroke is In most instances, an acute stroke is quite apparent
performing an unenhanced CT to rule out hemorrhage from the clinical presentation. However, the many mim-
and ensuring that the area of infarct at presentation (i.e., ics of clinical stroke include transient ischemic attacks
the total area of hypodensity in the CT scan) is less than (TIAs), syncope, dizziness, lightheadedness, seizures,
one third of the middle cerebral artery (MCA) territory. hypoglycemia, tumors, and demyelinating conditions.
If these inclusion criteria are met, the only treatments Similarly, not all new hypodensities on noncontrast
approved by the US Food and Drug Administration are CT represent a stroke. Multiple signs point to an acute
IV thrombolysis or clot retrieval. IV thrombolysis is rec- stroke on a non–contrast-enhanced CT, including (1) a
ommended only for those cases in which the time of focal area of parenchymal hypoattenuation, (2) cortical
onset of symptoms is known and in which fewer than swelling resulting in effacement of the normal gyral and
3 hours have elapsed from the time of onset to admin- sulcal pattern, (3) loss of gray–white differentiation, and
istration of IV tPA. Given these stringent requirements, (4) a dense vessel sign, typically the MCA or one of its
less than 20% of patients are triaged for evaluation and sylvian branches, reflecting thrombus within the lumen
less than 5% eventually receive IV thrombolysis. The of the involved vessel. Some signs of an ischemic stroke
MERCI clot retrieval device (Concentric Medical Inc, on CT can be subtle; however, with proper attention to
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 11

SECTION I
A B

C D
Figure 1-10 Multidetector computed tomographic images from contrast-enhanced computed tomographic angiography showing an internal
carotid artery aneurysm.

Non–contrast-enhanced
head CT
(signs of acute stroke)

Hemorrhage, mass, Area of hypoattenuation,

hydrocephalus dense vessel sign, or other
(BP control, CT angiogram, MRI,...) signs of acute stroke

CT angiogram
(determine the area
of vascular occlusion)

CT perfusion MRI with diffusion

(determine the area of weighted imaging (DWI)
infarct core and penumbra) MR perfusion

Figure 1-11 Sequence of imaging steps in the management of acute stroke.

12 Section I  Advanced Modalities: Protocols and Optimization

Figure 1-12 A: Pair of contiguous slices displayed using stan-

dard window-level setting (L = 80 HU, W = 20 HU) from a patient
who presented with acute stroke symptoms. The area of infarction
is difficult to discern. B: The same slices with a narrow window-
level setting (L = 32 HU, W = 8 HU). The subtle areas of loss of
gray–white differentiation in left frontal and parietal regions are
much more apparent and are concordant with later images show- C
ing fully developed infarcted regions (C).

detail and window-level settings, in most instances they width and level settings for the detection of acute stroke.
can be visualized within 6 hours of symptom onset. Specifically, they determined the sensitivity and specific-
Early during an acute stroke, the slight decrease in the ity of the standard center level and window width set-
CT number of the involved brain parenchyma is thought tings of 20 and 80 HU. These settings were compared
to be a result of cytotoxic edema, presumably from a fail- with variable soft-copy settings initially centered at a
ure of energy-dependent cell membrane pumps. Later, level of 32 HU and a width of 8 HU. They found that
vasogenic edema may be responsible for the apparent use of variable soft-copy settings improved the sensitiv-
drop in density. In the evolution of an infarct, a phe- ity of stroke detection from 57% to 71% without loss
nomenon called infarct fogging has been reported in of specificity. The fact that narrow window-level settings
which the hypoattenuation secondary to the infarct dis- help in the evaluation of subtle changes in attenuation
appears after 2 to 6 weeks. This is thought be the result is illustrated in Figure 1-12.
of higher-density cellular infiltrate in the infarction bed. Besides ruling out intracranial hemorrhage and dem-
The infarct reappears in the more chronic stage when onstrating the areas of infarctions, a noncontrast CT can
the cellular infiltrate clears and cavitary and/or encepha- sometimes show the acute thrombus responsible for the
lomalacic changes set in. vascular compromise. This finding pre­sents as a hyper-
In order to not miss the subtle changes associated dense segment of an intracranial vessel and can involve
with an acute infarct, it is important to use appropri- either an artery or a vein. The most common location
ate window width and level setting. Typically, for most of this sign is in the proximal MCA, resulting in the so-
parenchymal pathologies a window-level setting of ­ called dense MCA sign. In the anterior circulation, the
W = 20 HU and L = 80 HU is used. Lev and colleagues hyperdense vessel sign is highly specific for proximal
evaluated the use of nonstandard, variable window MCA and its sylvian branches. The sign is not as useful
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 13

SECTION I
A B

C
Figure 1-13 Middle cerebral artery (MCA) dot sign. A, B: Hyperdense left MCA showing acute thrombus on noncontrast computed tomogra-
phy. C: Computed tomographic angiography showing the corresponding cutoff in the left MCA.

in the posterior circulation. The prognostic value of this can introduce asymmetries that can be misinterpreted.
sign in predicting thrombolysis efficacy and for differ- The effect of many of these artifacts can be minimized
entiating between the so-called red and white clot has by incorporating coronal images in the reading routine.
been studied. Figure 1-13 shows the presence of hyper- At our institution, coronal images that correct for head
dense MCA in an acute stroke setting. Figure 1-14 shows tilt are reconstructed for all noncontrast CT scans per-
a slightly different and rarer presentation of this sign formed for the evaluation of head trauma. These views
from thrombosis of a deep vein that resulted in a venous can be constructed directly at the scanner and pushed
infarct (not shown in figure). to the PACS (Picture Archiving and Communication
Non contrast CT can suffer from a variety of artifacts System) along with the axial images. Our experience to
that degrade image quality. In order to avoid misinterpre- date reveals that these views are invaluable for ruling out
tation, it is essential to understand the genesis of these subtle subarachnoid hemorrhage, small SDHs adjacent
artifacts in order to properly account for them. Beam- to the falx and tentorial leaflets, blowout fractures of
hardening artifacts in the posterior fossa are ­common the orbital floor, and brain contusions, especially in the
and somewhat symmetric. The primary concern with so- anterior temporal and frontal lobes.
called spray or metallic artifacts emanating from aneu-
rysm clips, coils, or embolization material, such as Onyx CT Angiography
(ev3 Neurovascular, Inc, Irvine, CA), is that they can hide
important pathology such as hemorrhage, infarct, or CTA is the study of choice for all emergent and nonemer-
aneurysm neck in their vicinity. Improper positioning of gent neurovascular conditions, including acute stroke.
the patient resulting in a tilted reconstruction plane also Compared to MRI, it is faster, cheaper, more available,
14 Section I  Advanced Modalities: Protocols and Optimization

Figure 1-14 Noncontrast computed tomography (CT) showing a linear hyperdensity near the confluence of the vein of Galen and the straight
sinus (left) that appears as a filling defect on CT venogram (right), consistent with deep venous thrombosis.

Figure 1-15 Individual 1.25-mm computed tomographic angiographic images can be quite numerous and tedious to go through when the
scan is being checked at the scanner. It is possible to generate 30-mm-thick slabs at 5-mm intervals (left) (i.e., 25-mm overlap between adjacent
slabs) in all three planes. The thick slabs are much easier to review than the individual axial slices (right).

and less prone to artifacts. MRI may be useful as a is important that slabs overlap with each other so that
screening tool, especially when ionizing radiation is a the vasculature changes slowly as the images are paged
concern (e.g., in pediatric patients). However, CTA is the through. The technologist can generate these images at
confirmatory test and is competitive with catheter angi- the scanner in a matter of minutes, and all three planes
ography, the current gold standard for vascular imaging. can be generated equally easily while correcting for head
In an acute stroke setting, cervical and upper thoracic tilt. The views are extremely useful in providing a quick
vasculature should be evaluated in addition to the intra- wet-read in emergent situations and are quite appro-
cranial vasculature. A combined CTA of the head and priate for making triage decisions before the patient is
neck, from the aortic arch to the cranial vertex, can be removed from the CT table. Three-dimensional maximal
obtained with as little as 70 ml of IV contrast in less than intensity projection (MIP) images and curved reformats
15 seconds. Images should be acquired at slice thickness also are useful but require a dedicated core laboratory
of at least 1.25 mm, preferably with 50% overlap. In for generating the views.
order to facilitate quick visualization of the great arter- An area of hypoattenuation is a nonspecific find-
ies, thick 30-mm slabs with a reconstruction interval of ing on a noncontrast CT scan and does not necessarily
5 mm have proved to be quite effective (Figure 1-15). It represent an acute stroke. The etiology of this finding
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 15

may be revealed by CTA. If the hypoattenuation does, and the concomitant rise in venous pressure ultimately

SECTION I
in fact, represent an acute stroke, it may be the result result in a cortical venous infarction. Venous infarctions
of an embolus from a cardiac, carotid, or intracranial are frequently hemorrhagic and are commonly centered
arterial source. Arterial atherosclerotic plaque is most in the white matter or at the gray–white matter junc-
often the culprit. Cardiac etiologies include valvular tion. Sometimes only petechial hemorrhage occurs;
vegetations, tumors, endocarditis, and intracardiac however, overtly hemorrhagic venous infarction is not
right-to-left shunts (e.g., patent foramen ovale). A uncommon.
dissection or pseudoaneurysm also may result in an The causes of intracranial venous thrombosis are no
embolic phenomenon. In only a minority of cases different from those occurring elsewhere in the body.
does a venous compromise result in an infarction. They include a hypercoagulable state, dehydration,
Most of these etiologies of acute stroke can be directly extrinsic compression, or local invasion of a vein by
visualized on CTA of the head and neck (Figures 1-16 tumor, an adjacent infectious process (e.g., mastoiditis),
through 1-19). a low-flow state within the venous sinus, pregnancy, and
Given the high prevalence of cardiogenic acute the postpartum state. Oral contraceptives also have been
strokes, it now is possible to extend the field of associated with increased risk of venous sinus thrombo-
­coverage of CTA to include the heart in the evaluation. sis. No predisposing risk factors are identified in as many
Shapiro, Neilan, and colleagues showed the feasibility as 25% of patients with demonstrable venous conges-
of detecting left atrial (LA) appendage thrombus using tion resulting in regional ischemia and infarction. Just
CT. MDCT has sensitivity of 80%, specificity of 73%, as the intracranial arterial beds are well defined, the site
and negative predictive value of 92% for detection of venous thrombosis dictates the part of the brain that
of LA appendage thrombus. Therefore, a subgroup of will suffer infarction. For example, thrombosis of deep
patients at very high risk for LA appendage thrombus cerebral veins (e.g., basal vein of Rosenthal, internal
may benefit from the high negative predictive value of cerebral veins) typically results in thalamic infarction.
cardiac MDCT performed in conjunction with a stroke
CTA. In this protocol, gated helical cardiac acquisi- CT Perfusion (CTP)
tion is performed after a vertex-to-arch CTA is com-
pleted. Only 15 ml of additional contrast is needed to Millions of neurons and billions of synapses are esti-
complete the additional imaging. Figure 1-20 shows mated to be lost per minute during acute stroke. If
a thrombus in the LA appendage detected using this stretched out, the myelin fibers affected every minute by
protocol. acute stroke would measure in miles. The saying “time
Figure 1-21 shows a computed tomographic veno- is brain” is clearly apropos in an acute stroke setting.
gram (CTV) demonstrating the delta sign from a throm- Advanced neuroimaging is attempting to take this con-
bus in the superior sagittal sinus. The full extent of the cept one step further. Not only can brain tissue that has
dural sinus thrombosis can be appreciated in the 3-D infarcted be detected, but tissue that is at risk for infarc-
view after automatic bone subtraction. tion because of poor cerebral perfusion can be predicted.
Figure 1-22 shows an area of hypoattenuation, with The key tasks in an acute stroke setting are to exclude
internal areas of hyperattenuation, in the left middle intracranial hemorrhage, define the “core” of ­infarction,
and posterior cerebral artery territories. In the absence of locate the site of intraarterial thrombus responsible for
a prior history, the differential considerations for these the infarct, and assess the extent of additional brain
findings include (1) traumatic contusion, (2) hemor- parenchyma that is threatened if blood flow is not
rhage from hypertension, bleeding diathesis, amyloid restored.
angiopathy, or AVM, (3) infarction from one of many CT is quite accurate in detecting territorial infarcts;
different etiologies, and (4) hemorrhagic tumor. MDCT however, diffusion-weighted imaging (DWI) using MRI
can help narrow down the differential. Because the is more sensitive for detecting small lacunar and distal
area of signal abnormality does not conform to a sin- infarcts. MRI also can detect small, chronic microbleeds
gle vascular territory, an embolic infarct from a purely that may be missed by CT scan. Despite these limita-
arterial source is unlikely. In this case, CTA revealed the tions, a CT scanner typically is the imaging modality
intracranial arteries to be patent. Because the timing most widely available in an emergency room. Using
difference between the arterial and venous phases of a a CT scanner for processing all aspects of acute stroke
contrast bolus is small (intracranial circulation is a low- management is clearly quite attractive for delivering effi-
resistance circuit), most CTAs can be easily converted to cient care.
combined CTA/CTV by lengthening the duration of the Noncontrast CT and CTA are helpful in excluding intra-
bolus and acquiring the images approximately 10 sec- cranial hemorrhage and locating the site of the thrombus.
onds later than those for CTA. In this case, combined A CT perfusion scan aims to detect the mismatch between
CTA/CTV revealed complete occlusion of the left trans- the brain already infarcted at presentation (“core”) and
verse sinus, confirming a venous infarct. that at risk of infarction (“penumbra”). The amount
Occlusion of a venous sinus or cortical vein may be of mismatch, if it can be efficiently derived, then can
initiated by a partial thrombus or extrinsic compres- be factored into patient selection for thrombolysis.
sion. This initial insult subsequently progresses to com- CT perfusion imaging uses the dynamics of first-pass
plete occlusion. Once initiated, a thrombus may extend bolus through the brain parenchyma to derive perfusion
in retrograde fashion into the veins draining into the maps. In its idealized form, CT perfusion is based on
involved sinus. The resulting lack of venous outflow administering a short contrast bolus and observing its
16 Section I  Advanced Modalities: Protocols and Optimization

Figure 1-16 Computed tomography angiography of carotid bifur- Figure 1-17 Pseudoaneurysm resulting in dilation of the distal left
cation in two different patients. Left: Extensive noncalicified plaque internal carotid artery (LICA) in a three-dimensional maximal inten-
causing severe stenosis of the proximal left internal carotid artery sity projection view.
near the origin. Right: Hairline lumen in the proximal external carotid
artery. LCCA BIF, left common carotid artery bifurcation).

A B
Figure 1-18 Posttraumatic dissection of the vertebral artery. The intimal flap is clearly visualized in the curved reformatted view in A.
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 17

SECTION I
Figure 1-19 Left internal carotid artery (LICA) dissection, confirmed by visualization of an intimal flap on an oblique maximal intensity pro-
jection image (left), resulting in partial occlusion of the left petrous internal carotid artery distal to the dissection.

Figure 1-20 Left atrial appendage (LAA) thrombus. Neurologic computed tomographic angiography extended to include the LAA shows a
thrombus (asterisk) responsible for acute stroke.

Figure 1-21 Delta sign of venous sinus thrombosis. Axial postcontrast images showing the delta sign from a thrombus in the superior sagittal
sinus. The full extent of the thrombus can be appreciated in the three-dimensional view after automatic bone removal.
18 Section I  Advanced Modalities: Protocols and Optimization

Figure 1-22 Infarct with hemorrhagic

conversion that does not fall in a single
arterial territory. Computed tomography
angiography/computed tomography venog-
raphy demonstrates patent intracranial
arteries and dural venous sinus thrombo-
sis, confirming this infarct to be of venous
origin.

A B
Figure 1-23 Computed tomographic perfusion maps derived from a sequence of images such as that shown in A. This sequence documents
the temporal evolution of contrast bolus through the brain parenchyma. In one type of processing, arterial input function and venous outflow
functions are derived from this sequence (B).
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 19

evolution in the brain. Repeated CT scans through the to deliver contrast at such a high rate. Current scanner

SECTION I
brain parenchyma under observation yield a time-atten- technology allows a 2- to 4-cm slab to be observed.
uation curve for each pixel that documents the changes Generally two such slabs are required to study both the
in tissue contrast during the bolus passage. CT perfusion middle and anterior cerebral artery territories. One per-
software is used to process this sequence of images to fusion slab may suffice if the presentation and symp-
derive cerebral blood flow (CBF), cerebral blood vol- toms strongly point to one territory over another. Newer
ume (CBV), mean transit time (MTT), and vascular per- scanners also offer a shuttle mode in which the patient
meability (kPS) information from dynamic changes in table is moved back and forth in order to increase the
contrast enhancement. axial coverage along the Z-direction at the expense of
Good histologic evidence exists that the area of temporal resolution. The exact coverage of a single slab
restricted diffusion on an MRI scan closely corresponds using these newer shuttle modes depends on the equip-
to the tissue that has infarcted. It is widely believed that ment vendor and the make and model of the scanner.
in a perfusion scan using MRI, the so-called ischemic Figure 1-23 schematically depicts the set of steps
penumbra or “at-risk” brain is captured by the MTT and required to make CT perfusion maps. These maps are
CBF maps. However, because magnetic resonance perfu- derived from a sequence of images that documents
sion is not a quantitative map, it is difficult to set a strict the temporal evolution of a contrast bolus through
threshold to demarcate the area of “benign oligemia” the brain parenchyma. A variety of software packages
from those that will proceed to infarction if blood flow are available to process the perfusion image sequence.
is not reestablished. In one type of processing, arterial input and venous
Unlike MRI, CT provides quantitative maps of CBV, outflow functions are automatically derived from this
CBF, and MTT. There is growing evidence that CT CBV sequence. These functions are shown in Figure 1-23B.
maps, just like DWI scans, roughly correspond to the In addition, the opacification curve for each voxel can
brain parenchyma that has already infarcted. MTT and be mapped and will have a shape quite similar to that
CBF maps describe the area that is at risk or has already shown in Figure 1-23B. A combination of the arterial
infarcted. The difference between the two, therefore, cor- input functions and the time-opacification curves is
responds to the ischemic penumbra that is at risk. The used to derive the perfusion maps (Figure 1-24) that
exact threshold for delineating the boundary between depict CBV, CBF, MTT, and permeability for each voxel
these areas is a topic of current active research. in the imaged volume. Generally speaking, CBV corre-
Construction of reliable CT perfusion maps requires sponds to the area under the time-opacification curve,
delivering a tight bolus and observing an axial slab con- CBF is proportional to the maximum upslope of the
tinuously for about 40 to 60 seconds. Typically, a 40-ml curve, and MTT is proportional to time to peak from the
contrast bolus is delivered at 7 ml/s through a peripheral start of bolus arrival.
IV line. An 18-gauge or larger-bore IV line is necessary Excellent software packages that fully automate the
generation of perfusion maps are available. The soft-
ware automatically identifies the arterial input function
and the venous outflow (typically using a major venous
sinus) required to compute perfusion maps. Clinical
studies have shown that the maps generated automati-
cally are essentially identical to those made by experts.
Of note, other perfusion packages that do not rely on
the arterial input function are available. A comprehen-
sive discussion of the different algorithms for generation
of perfusion maps is beyond the scope of this chapter.
Software systems also exist for automatic segmentation
of core and penumbra. With the degree of automation
that is available, concerns about workflow should not
prevent use of CT perfusion for the evaluation of acute
stroke patients.

Problem-Solving Tool/Cases
in Stroke
Two cases are presented that demonstrate the power of
CTP in triaging acute stroke patients based on the size of
the tissue at risk. Figure 1-25 shows the case of a patient
who presented with acute MCA syndrome. The presen-
tation MRI showed a DWI defect restricted to the insula
and frontal operculum. MTT and CBF maps demon-
strate that the entire left MCA territory is at risk. This
Figure 1-24 Perfusion maps depicting mean transit time (MTT), patient was beyond the time window for IV thromboly-
cerebral blood volume (CBV), cerebral blood flow (CBF), and perme- sis using tPA. She was emergently taken to the neuro-
ability (kPS) for each voxel in the imaged volume. interventional suite for catheter-assisted thrombectomy.
20 Section I  Advanced Modalities: Protocols and Optimization

DWI MTT

CBF CBV

Figure 1-25 Diffusion-weighted images showing the core of the infarct at presentation and the three perfusion maps derived from computed
tomography.

Figure 1-26 Anteroposterior view showing acute occlusion of the left middle cerebral artery stem (A) and blood flow after catheter-assisted
thrombectomy (B).
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 21

Figure 1-26 shows the angiogram before and after the For postcontrast imaging, the contrast agent is slowly

SECTION I
procedure. Blood flow to the left MCA territory was fully infused, and imaging is conducted 2 to 5 minutes after
restored. The discharge DWI scan for this patient was the end of infusion. This timing is different from that
quite similar to that of the core of the infarct, and the used in contrast-enhanced CTA or CTV because the
procedure was successful in arresting the progression of process being imaged has a very different time con-
core into the ischemic penumbra. stant. In CTA or CTV, the arterial or venous phase of the
Figure 1-27 shows the case of a patient with a perfu- contrast bolus is of interest. These phases commence
sion deficit in the posterior left MCA territory. There is a ­approximately 20 or 40 seconds after the start of IV con-
large mismatch between the core and the deficit on CBF trast injection, depending on the cardiac ejection frac-
and MTT maps. This patient was beyond the window for tion of the patient. In tumor imaging, the imaging is
IV or arterial intervention. On the 48-hour DWI scan, delayed by several minutes. The rationale for relatively
the infarct had grown to involve the additional tissue delayed imaging is to give the contrast enough time to
at risk. The final core of the infarct nearly matched the “leak out” of the compromised blood–brain barrier in
MTT and CBF abnormality originally seen 2 days earlier. the tumor vasculature. Because different tumors show
Derivation of perfusion maps depends on the deliv- peak opacification at different times, no single “perfect”
ery of contrast to different portions of the brain. If time applies to all neoplastic conditions. However, if a
the main arteries supplying a portion of the brain are patient is known to have a primary tumor and the ques-
narrowed, delivery of contrast to that portion will be tion is that of ruling out intracranial metastatic disease,
delayed. Unless proper care is taken to ensure that the the timing of the scan may be appropriately configured.
arterial input function is given time to peak and to return Melanoma, renal cell carcinoma, choriocarcinoma, sar-
to near baseline value, the software may misinterpret comas, neuroendocrine tumors, and thyroid cancers
delayed flow and present it as diminished perfusion. typically show early enhancement.
This is shown in Figure 1-28. Blood flow into the left Despite an optimal imaging protocol, MDCT is not
MCA territory was delayed because of complete occlu- as sensitive as MRI for detection of intracranial primary
sion of the proximal left internal carotid artery (ICA) and metastatic disease. Nonetheless, MDCT provides
as demonstrated in the CTA. The arterial input function essential information about intracranial neoplasms and
was not given enough time to return to baseline. The should be obtained for more complete characteriza-
resulting perfusion maps show a large perfusion deficit tion. MDCT is essential for postoperative evaluation of
in the left MCA territory even when the patient had no tumors and any associated surgical complications. If the
acute stroke. Similar situations may arise in the setting patient cannot undergo an MRI scan (e.g., because of
of low ejection fraction, total occlusion of an artery, or a pacemaker), a contrast-enhanced CT scan may be the
transient atrial fibrillation. only alternative for detection and follow-up of intracra-
nial neoplastic conditions.
MDCT IN NEOPLASTIC CONDITIONS MDCT contributes to the diagnosis and characteriza-
tion of intracranial neoplastic disease, either primary or
MDCT provides a quick way to detect primary and meta- metastatic, in three essential ways:
static disease in the brain. A non–contrast-enhanced CT 1. The internal density and composition of the tumor
is relatively insensitive for detection of neoplastic disease, can be readily studied using CT. For example, CT
especially when the tumor burden is small. Therefore, a is very sensitive in detecting internal calcifications,
postcontrast CT should always be obtained when evaluat- necrosis, foci of hemorrhage, and fatty deposits.
ing neoplastic conditions using CT. For certain conditions, 2. The presence and extent of calvarial or skull base
both precontrast and postcontrast imaging are warranted. involvement by tumor are better depicted by CT than
For example, if hemorrhage is suspected or the neoplas- MRI.
tic condition being ruled out is intrinsically hyperdense 3. The presence of neovascularity can be evaluated by
(e.g., melanoma, small blue round cell tumors, densely CT perfusion studies, thus narrowing the differential
packed lymphomas), then a noncontrast CT in addition diagnosis or leading to a diagnosis.
to a postcontrast scan should be obtained. Small meta-
static foci can be hard to see in a contrast-enhanced CT Problem-Solving Tool/Cases
image (Figure 1-29). Therefore, attention to the scanning
in Neoplastic Conditions
protocol is of utmost importance in these cases.
For the scanning protocol, 2.5- to 5-mm thick slices The remainder of this section illustrates typical applica-
generally are sufficient. Because most institutions now tions of MDCT as a problem-solving tool in neoplastic
acquire images in a helical mode, thinner overlapping conditions.
slices can be reconstructed retrospectively if they are Figure 1-30 shows the case of a 45-year-old woman
required to answer a specific clinical question. Such ret- who presented with a history of slowly progressive spas-
rospective reconstruction is feasible as long as the raw ticity of the upper and lower limbs. CT scan showed
projection data still are available in the scanner. Coro- an extraaxial mass wrapped around the medulla with
nal and sagittal images should be reconstructed and considerable mass effect on the brainstem. At MRI, the
reviewed to increase the sensitivity of detection. Bone mass had a cystic component centrally and T2 hypoin-
kernel reconstructions should be obtained in addition tense component anteriorly. CT feature of uniform
to soft tissue kernels to increase sensitivity to bony pri- ­hyperdensity in the anterior component suggested a
mary and metastatic disease. ­diagnosis of a “white epidermoid.” DWI scan confirmed
22 Section I  Advanced Modalities: Protocols and Optimization

C
Figure 1-27 A: Admission cerebral blood volume, cerebral blood flow, and mean transit time for a patient who presented with acute stroke.
B: Diffusion-weighted images at 24 hours showing the core of the infarct. C: Diffusion-weighted images 48 hours after presentation. Note that the
final infarct size is close to that predicted by the cerebral blood flow map.
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 23

SECTION I
A

C
Figure 1-28 A: Contrast-enhanced computed tomography showing inability to trace the internal carotid artery. B: Left middle cerebral artery
(MCA) is less dense compared to right MCA because of delayed bolus arrival. C: Perfusion map showing artificial mean transit time changes in
the left hemisphere.
24 Section I  Advanced Modalities: Protocols and Optimization

Figure 1-30 Plain computed tomographic section at the level of

the medulla showing a hyperdense mass wrapped around the anterior
Figure 1-29 Contrast-enhanced computed tomographic slice through medulla with a cystic component in the region of the fourth ventricle.
the posterior fossa demonstrating an amorphous area of contrast enhance- Magnetic resonance imaging with diffusion imaging (not shown) con-
ment in a patient known to have colon cancer. This finding confirmed firmed an epidermoid tumor in this location.
intracranial metastatic disease in the patient, who could not undergo
magnetic resonance imaging scan because of a cardiac pacemaker.

Figure 1-31 Noncontrast computed tomographic slice at the level

of the basal ganglia showing a central, well-defined, hyperdense mass
along the midline, near the foramen of Monro in the anterior third ven-
tricle, with classic features of a colloid cyst on computed tomography.
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 25

SECTION I
A B
Figure 1-32 A: Postoperative computed tomography (CT) of a patient with a right cerebropontine angle mass, extending into the right internal
auditory canal, showing hyperostosis of the petrous ridge and the mastoid air cells on the ipsilateral side. B: Magnetic resonance imaging of the
same patient. The hyperostosis demonstrated by CT scan is suggestive of a meningioma.

the diagnosis of an epidermoid. Epidermoid cysts usu- the suprasellar cistern suggesting the diagnosis of a cra-
ally are hypodense but infrequently are hyperdense, as niopharyngioma, a diagnosis that is classically made on
illustrated in this case. CT. However, a soft tissue mass confined to the supra-
Hyperdensity on CT may reflect dense cellularity, sellar region, causing hydrocephalus due to foramen of
diffuse calcification, mineralization (e.g., siderosis), or Monro obstruction, could represent a pilocytic astrocy-
high protein content in an otherwise cystic structure. toma, as illustrated in Figure 1-35.
Figure 1-31 shows an example of a colloid cyst, which is Interaction of a mass with adjacent bone is well dem-
characteristically seen in this location. The diagnosis of onstrated by MDCT. Figure 1-36 shows a soft tissue mass
a colloid cyst is virtually confirmed by the CT scan. that is destroying the lesser wing of the sphenoid. This
Bone remodeling is better illustrated on CT than MRI. soft tissue mass projects into the middle cranial fossa,
Figure 1-32 shows the postoperative scan of a 40-year- displacing the temporal lobe, and abuts the left cavern-
old man with a right-sided, peripheral, posterior fossa ous sinus. Small calcific foci are located within the mass.
mass. The CT section confirms hyperostosis of the right Histopathologic examination revealed the mass to be an
petrous ridge, a classic feature of a meningioma. eosinophilic granuloma.
For a mass adjacent to important vascular structures, Pituitary macroadenoma is typically known to extend
a wealth of information can be derived from CTA study. into the suprasellar cistern and in up to 40% of cases
CTA or CTV can be used to study tumor vascularity, can invade the cavernous sinus. Cavernous sinus inva-
mass effect on the adjacent vessels and their dominant sion is determined by encasement of the ICA, which can
blood supply, venous drainage and their patency. Figure be well identified on CTA (Figure 1-37).
1-33 shows examples of high-convexity meningiomas Figure 1-38 illustrates a pitfall of CT and the method
infiltrating the superior sagittal sinus. MDCT demon- for getting around it. The initial CT scan of a 4-year-old
strates complete occlusion of the midsegment of the child who presented with abdominal pain, vomiting,
sinus is case A, with collaterals and incomplete occlu- and recent sinusitis treated with antibiotics was read as
sion in case B. normal. A closer look at the skull base in the vicinity
CT can readily show the presence and distribution of of the cavernous sinuses shows an extraaxial hyperdense
calcifications in a mass, narrowing the differential diag- mass that was misinterpreted as volume averaging and
nosis. For example, suprasellar masses can have a broad beam hardening artifact. The trick here is to review coro-
differential that includes pituitary macroadenoma, cra- nal and/or sagittal reformations, which clearly demon-
niopharyngioma, cavernous ICA aneurysm, germinoma, strate bulging cavernous sinuses, a feature that cannot
and metastases. This differential can be considerably be attributed to CT artifacts. A repeat scan 1 week later
narrowed by the extent of the mass, enhancement pat- showed that the mass had grown significantly in the
tern, calcifications, blood flow, and native CT density. interval. Stereotactic biopsy confirmed Burkitt lym-
Figure 1-34 shows the case of a young child who pre- phoma, which was hyper­dense on CT.
sented with increased intracranial pressure and vision This case illustrates another key point: even soft tis-
loss. The image clearly shows a calcified cystic mass in sue masses can show differences in CT attenuation that
26 Section I  Advanced Modalities: Protocols and Optimization

B
Figure 1-33 A: Case A. Left, Left high convexity parasagittal meningioma causing complete occlusion of the midsegment of the superior sagittal
sinus with formation of collateral venous drainage around it. Right, Computed tomographic venogram confirms complete occlusion of the seg-
ment of the superior sagittal sinus. B: Case B. Left, Posterior left parasagittal meningioma abutting and indenting the superior sagittal sinus with-
out occluding it. Right, Computed tomographic venogram confirming patency of the superior sagittal sinus at the site of indentation by the mass.
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 27

SECTION I
Figure 1-34 Axial section from a non–contrast-enhanced com- Figure 1-35 Pilocytic astrocytoma in the suprasellar cistern causing
puted tomographic (CT) scan at the suprasellar cistern level showing a dilation of the temporal horns of the lateral ventricles due to compres-
well-defined rounded lesion with some cystic components around the sion of the foramen of Monro.
central chunky calcification as well as linear calcifications in the rim of
the cystic components. The noncontrast CT appearance is highly sug-
gestive of a craniopharyngioma.

Figure 1-36 Eosinophilic granuloma eroding the left lesser wing of the sphenoid and left squamous temporal bone. This mass also shows
punctate calcific foci and a soft tissue component that is indenting on the left temporal lobe and is extending medially to abut the lateral wall of
the cavernous sinus.
28 Section I  Advanced Modalities: Protocols and Optimization

Figure 1-37 Large bilobed, enhancing sellar/suprasellar mass that is expanding the sella and invading the right cavernous sinus representing a
typical pituitary macroadenoma. The right cavernous internal carotid artery is completely encased, and there is a convex lateral margin. A lobu-
lated component in the right aspect of the perimesencephalic cistern is seen indenting on the right posterior cerebral artery and proximal right
middle cerebral artery without compromising its lumen. The optic chiasm is compressed and displaced, and it cannot be identified separately
from the mass.

may be useful in characterizing a mass. For example, on MRI because of susceptibility artifacts from air. CT not
densely cellular masses have slightly higher ­attenuation, only shows the pathology but also the exact place where
a property common to high-grade lymphomas. This is the fistulous connection is formed. Another case of bone
illustrated in Figure 1-39, which shows the case of a erosion by neuroblastoma is shown in Figure 1-44.
55-year-old man who presented with new-onset seizures.
On non–contrast-enhanced CT imaging, he was found MDCT IN EVALUATION OF SPINE
to have a large mass in the left cerebral hemisphere. This
mass, which is slightly hyperdense compared with nor- MDCT plays a major role in the diagnosis and manage-
mal gray matter and hyperdense compared to normal ment of various conditions involving the spine. The fol-
white matter, crosses the midline and predominantly lowing subsections briefly outline and illustrate the role
involves the white matter, with marked edema. MRI with played by this modality in the management of trauma,
gadolinium showed the mass to be brightly enhanc- infection, neoplastic conditions, and myelography.
ing. MRS showed a high choline peak with an elevated
choline-to-creatine ratio and no lipid component. The Spinal Trauma
differential included glioblastoma multiforme and lym-
phoma. However, the CT finding of a hyperdense mass The efficacy of CT, along with its high sensitivity and
favors lymphoma. Stereotactic biopsy was performed, specificity, in detecting traumatic fractures of the spine
and histopathology confirmed a lymphoma. is well established. Axial CT significantly outperforms
CT can demonstrate pathologies affecting the calvaria plain radiography in the evaluation of trauma to the
with better sensitivity and detail than MRI. Although CT spine and has largely supplanted it in the management
cannot demonstrate bone edema as well as MRI can, of acute trauma. The excellent structural details of mul-
the extent of cortical involvement or destruction can tiplanar reconstructions and 3-D images help in better
only be demonstrated on CT. Figures 1-40 through 1-42 visualizing spatial relationships. MDCT has become
show some specific conditions in which CT shows char- the standard of care for classification and preoperative
acteristic findings pointing to a diagnosis. planning for acute traumatic fractures. CT is much more
MDCT not only shows the primary tumor and it’s inter- valuable than MRI in the detection of subtle fractures
relationship with the adjacent vessels, it often can dem- because of its availability and lack of contraindications.
onstrate any associated complications. For example, if a MRI is reserved for evaluation of ligamentous injury.
mass is compressing an important vascular structure or is State-of-the-art MDCT scanners are capable of
eroding the bone to form a fistulous connection between approximately 0.5-mm isotropic resolution. Thin
two compartments, CT may be used as a problem-solving CT slices, combined with low pitch and overlapping
tool. Figure 1-43 shows the case of a chordoma that had reconstructions, result in marked improvement in the
eroded the skull base, causing extensive pneumocephalus. visualization of subtle fractures. It is important to use
The same finding would be suboptimally ­demonstrated a sharp kernel, low slice thickness, and appropriate
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 29

SECTION I
A B

C D

Figure 1-38 A: Axial computed tomographic (CT) image showing a hyperdense mass along the outer margin of the right cavernous sinus.
B, C: T2 and postcontrast T1-weighted images confirming midline mass in the posterior ethmoid region, encroaching on the right cavernous sinus.
D: CT scan obtained 1 week after the image shown in A showing increased size of the hyperdense, enhancing mass.
30 Section I  Advanced Modalities: Protocols and Optimization

Figure 1-39 A: Computed

tomographic scan showing
left-sided mass in the white
matter that is hyperdense
compared with normal
white matter and isodense
compared to gray matter.
B: Post-gadolinium mag-
netic resonance imaging scan
showing a predominantly
left-sided mass that is infil-
trating and extending across
the body and splenium of
the corpus callosum to cross A B
the midline.

sagittal and coronal reformations when analyzing spi- facet of C5 is easily visualized on these views. Figures
nal CT. Figure 1-45 shows the importance of appro- 1-46C and 1-46D show the same pathology at the tho-
priate choice of scan and reconstruction parameters in racic level.
a trauma setting. At a slice thickness of 2.5 mm and Neural foraminal compromise or widening after
pitch of 1:1, the fracture in the right posterior arch of trauma can be well appreciated on MDCT. Posttrau-
C1 was not apparent and initially was missed. How- matic pseudomeningoceles occur due to avulsion of
ever, with a decreased slice thickness of 1.25 mm and nerve roots within the dura. The resulting saccular
pitch of 0.5:1, the fracture became more apparent on pockets of cerebrospinal fluid that extend through the
CT scan performed after 1 week. In general, decreasing neural foramen are best seen on coronal images. Mini-
the pitch, along with the decrement in the slice thick- mum intensity projection images after CT myelography
ness, may allow visualization of an otherwise occult are excellent for demonstrating these dural defects and
fracture. associated nerve roots (Figure 1-47).
With the advent of MDCT, primarily by virtue of
oblique reformations and 3-D display technology, Preoperative and Postoperative
fracture classification has become easier and more
Evaluation
straightforward. Although extensive literature exists
on determining which fractures are unstable based CT is an excellent modality for preoperative and post-
on radiographs, the task is considerably simplified operative evaluation. With the improved multiplanar
using multiplanar CT images. In simplified terms, a and 3-D reconstructions, preoperative assessment of
“major” cervical injury includes any of the following: complex spinal deformities has become routine prac-
(1) displacement of more than 2 mm in any plane, tice. Preoperative CT scan defines the anatomy and
(2) widening of the vertebral body, (3) widening of avoids any unexpected intraoperative posterior ele-
the interspinous or interlaminar line, (4) widened ment deficiencies. Because of its high resolution and its
facet joints, (5) posterior vertebral body line disrup- ability to obtain oblique views retrospectively, CT pro-
tion, (6) widening of the disc space, (7) burst fracture, vides superior visualization of the bony anatomy. In
(8) unilateral or bilateral locked/perched fractures, cases of severe scoliotic deformity, MRI can be limited
(9) hangman’s fracture, (10) odontoid fracture, and because only a select number of planes can be speci-
(11) occipital condyle fracture. All other types of frac- fied and obtained. Using CT, curved reformats can be
tures may be considered “minor.” performed and the spine “straightened” out in order
to elicit the relationship of the nerves with respect to
Problem-Solving Tool/Cases in the the neural foramina. One such example is shown in
Figure 1-48.
Spine
Although CT produces metallic artifacts in the plane
MDCT is helpful in the detection of the type of fracture, of the axial slice, the distribution of the artifacts is very
the extent of trauma, and any associated complications. different from that in MRI. In MRI, typically a wide
Figures 1-46A and 14-6B show a major injury of the area surrounding the metal is compromised. Using
­cervical spine seen via sagittal and 3-D surface-rendered appropriate oblique views, the artifacts can be thrown
views. A unilateral locked/perched inferior articular off the plane of abnormality in order to demonstrate
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 31

certain pathologies. An example is shown in Figure

SECTION I
1-49. Although MRI is better for visualizing nerves and
soft tissue abnormalities, the type of nerve impinge-
ment shown in this figure would be very difficult to
demonstrate using MRI due to the metallic artifacts.
However, appropriately angled oblique images clearly
­demonstrate impingement of the L5 nerve root from
malpositioned hardware.

Spinal Infections
Infective spondylodiscitis commonly presents as simple
backache. This diagnosis is more effectively made using
MRI but also can be made using MDCT. CT scan can
show the extent and type of infection causing spondylo-
discitis. Assessment of the degree of canal or foraminal
compromise and bony destruction is better performed
using MDCT than MRI. Signs that differentiate between
infection and other conditions, such as neoplasm, have
been described. CT can provide maps for intraoperative
image-guided biopsy.
In the setting of vertebral body or disc infection, CT
is very effective in demonstrating erosion along the end
plates. Coronal and sagittal images enable detection of
disc involvement and loss of height. Prevertebral and
paravertebral components of the infective process are
easily identified. Paraspinal abscesses have a character-
istic fluid density with peripheral rim enhancement.
Any epidural component of an abscess can be identi-
fied using CT, although MRI is more sensitive. Use of
contrast improves detection of an infected disc, which
shows abnormal enhancement.
Although CT is by no means definitive, it can guide
in differentiating the causative organism in spinal infec-
tions. The features that favor a pyogenic abscess include
Figure 1-40 Sagittal, axial, and coronal computed tomographic greater sclerosis and erosions along the end plates, exis-
slices showing classic features of fibrous dysplasia of the sphenoid tence of necrotic tissue, and greater involvement of the
bone, such as expansion of the sphenoid bone with ground-glass adjacent disc, which shows abnormal enhancement.
appearance with associated distortion of the optic foramina. However, in tuberculous spondylodiscitis, sclerosis

Figure 1-41 Multiple small, similar-sized, teardrop- or raindrop-shaped lytic lesions throughout the skull representing multiple
myeloma.
32 Section I  Advanced Modalities: Protocols and Optimization

A B
Figure 1-42 A: Computed tomographic section of the brain in the high vertical region showing widened diploic space with cortical thicken-
ing, coarse trabeculae, and marked sclerosis of the skull. A large soft tissue mass with a necrotic center is replacing the left frontal bone. These are
classic findings of Paget disease with the soft tissue mass representing malignant transformation. B: Skull radiograph showing the cotton-wool
appearance with lytic component in the left frontal region representing malignant transformation.

Figure 1-43 Sagittal computed tomographic reformation

from multidetector computed tomography of a 65-year-old
woman who presented with severe headache. Extensive pneu-
mocephalus due to a defect in the clivus (arrow) is seen. Inset:
Magnified view showing the communication between the sphe-
noid sinus and the posterior fossa responsible for the pneumo-
cephalus.

t­ ypically is minimal, and only a thin enhancing rim may for an epidural abscess. The advantages of CT in the
be seen around the necrotic components. In Koch spine, diagnosis of an epidural abscess include (1) possible
CT may identify subligamentous spread of infection detection of the source of infection, spondylitis, disci-
and intra-osseous abscesses within the vertebral bodies. tis, or facet joint infection; (2) detection of the extent
Figure 1-50 shows a case of spondylodiscitis. Spinal of epidural abscess; and (3) preoperative planning for
brucellosis, an uncommon spinal infection, is known image-guided aspiration and biopsy for diagnosis.
to have a “cauliflower” appearance of lytic lesions with
sclerosis along the margins of the lesions. Spinal Tumors
Epidural abscess, a surgical emergency, is rarely
encountered in present-day clinical practice. However, Early detection of a spinal tumor is possible on CT if a
a young patient with rapid onset of infective symptoms, lytic or sclerotic component is present. In case of diffuse
or a spinal level quadriparesis should undergo a workup marrow infiltrating tumors, CT may be less valuable.
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 33

subsections: temporal bone, orbital pathologies, and

SECTION I
neck tumors/masses.

Temporal Bone
As has been illustrated in other sections, MDCT is an
excellent tool for imaging bony pathology. This is espe-
cially useful for temporal bone and for structures embed-
ded within it because of their small size and intricate
interrelationships. MDCT is the preferred modality for
imaging the temporal bone and its associated patholo-
gies. Many congenital abnormalities, such as cochlear
aplasia, Mondini malformation, anomalous course of
the seventh and eighth cranial nerves, otosclerosis, and
tympanosclerosis, are readily demonstrated by MDCT if
proper attention is paid to the imaging protocol.
An ideal protocol for temporal bone imaging entails
very thin nonoverlapping slices. Typically, slices as thin
as 0.5 mm, reconstructed with bone kernel, are required
to visualize the small structures of the temporal bone.
The anatomy and the structures within the temporal
bone are not specifically aligned with the three ­cardinal
Figure 1-44 Young male who presented with left-sided proptosis. planes of the body. For example, the superior semi-
Axial computed tomographic (CT) section showing destruction of circular canal (sSCC) is oriented approximately 45
the lesser wing of sphenoid on the left side with a large soft tissue degrees from both the sagittal and coronal planes. The
component protruding into the left orbit causing proptosis. CT shows native axial dataset should be reformatted in specially
the extent of cortical destruction from this biopsy-proven neuroblas-
toma. oriented oblique planes to optimize visualization. The
two most commonly used planes are the Stenvers plane
and the Pöschl plane. The Pöschl plane approximates
In detecting tumors, CT is more useful than conven- the plane of the sSCC (Figure 1-53). The Stenvers plane
tional radiography for evaluating lesion location and is perpendicular to both the axial plane and the Pöschl
analyzing bone destruction and condensation. plane. The Stenvers plane shows the upper cortex of the
A “bubbly” lytic lesion that extends across vertebral sSCC in perfect cross section and is optimal for dem-
levels likely is a giant cell tumor or aneurysmal bone onstrating the integrity of the wall of the upper arc of
cyst. The latter is more common in the younger age the sSCC.
group and in the posterior elements. A solitary expans- The Stenvers and Pöschl orientations can be pre-
ile lytic lesion could also represent a plasmacytoma or scribed by the technologist at the scanner and the
a lesion in multiple myeloma. Many solitary lesions, resulting image data should be archived along with the
such as bone island, osteoid osteoma, osteochondroma, axial dataset. For prescribing these planes, the plane of
chondrosarcoma, vertebral hemangioma, and aneurys- the lateral semicircular canal can be used to define the
mal bone cyst, have characteristic features on CT. For true axial plane. On the true axial dataset, the sSCC
example, an isolated bone island is a focal, well-circum- can be used to prescribe the Pöschl plane; the Sten-
scribed osseous density within the marrow. An osteoid vers plane is perpendicular to this plane. In general,
osteoma demonstrates extensive sclerosis with a cen- the Stenvers plane is approximately parallel to the
tral lytic nidus. A hemangioma shows a typical “cordu- petrous ridge, and the Pöschl plane is perpendicular
roy” appearance, and aneurysmal bone cyst is a bubbly to the long axis of the petrous ridge. Visualization of
lesion. pathologies, such as sSCC dehiscence, cochlear mal-
Mixed lesion with lytic, sclerotic, and soft tissue com- formations, and vestibular anomalies, is facilitated by
ponents could represent a lymphoma or chordoma. The these planes.
latter is more commonly encountered in the sacrum. The sSCC dehiscence syndrome is a typical pathol-
Figures 1-51 and 1-52 illustrate some examples of these ogy that shows the power of MDCT. This syndrome,
entities. originally described in an article in 1998, requires
demonstration of a very small defect in the bony wall
CT IN HEAD AND NECK IMAGING of the sSCC. Even a small sliver of bone overlying the
SCC excludes the diagnosis of this syndrome. High-
Head and neck pathologies and their associated imag- resolution imaging and proper attention to protocol
ing findings are discussed in detail in Chapter 19. This are crucial to offset partial volume effect. Figure 1-54
section reviews and highlights areas where MDCT shows CT images from a case demonstrating a defect
is ­especially useful in evaluating these pathologies. in the sSCC.
The role of this modality as a problem-solving tool Superior semicircular canal dehiscence is only one
in this field is illustrated with the help of representa- of many pathologies that may result in the formation
tive ­examples. This section is divided into three main of a “third window” into a semicircular canal causing
34 Section I  Advanced Modalities: Protocols and Optimization

A B

C D
Figure 1-45 Multiple images of a subtle fracture in the right posterior arch of C1. A: Standard kernel, slice thickness 2.5 mm, pitch 1:1. B: Bone
kernel, slice thickness 2.5 mm, pitch 1:1. C: Standard kernel, slice thickness 1.25 mm, pitch 0.5:1. D: Bone kernel, slice thickness 1.25 mm, pitch
0.5:1. This fracture is not visible at slice thickness 2.5 mm and pitch 1:1 either using the standard kernel (A) or the bone kernel (B). The fracture
becomes more apparent when pitch 0.5:1, slice thickness 1.25 mm, and standard reconstruction kernel are used (C). It becomes even more appar-
ent after 1 week (D) when a sharper bone kernel with thinner slices and lower pitch is used (white arrow).

Tullio phenomenon. The hallmark of Tullio phenom- MDCT is the modality of choice for depicting trauma
enon is dizziness in response to loud sound. Tullio to temporal bone. Traumatic fractures of the temporal
phenomenon also results in specific eye movements bone can be divided into those that are oriented along
that depend on the semicircular canal involved. For the long axis of the petrous pyramid and those that
example, a third window in the lateral SCC results in a are perpendicular to it. These two fracture types result
horizontal nystagmus, whereas that in the sSCC causes in very different symptoms and can be readily distin-
vertical nystagmus with an inward torsion (45-degree guished using MDCT. A transverse temporal bone frac-
tilt of canal) or an opposite direction nystagmus with ture is shown in Figure 1-58. Such fractures account for
Valsalva. Entities that can cause a third window into about 10% to 30% of all temporal bone fractures and
the SCC include cholesteatoma, syphilis, and iatro- typically are the result of blunt trauma to the occiput.
genic reasons. All of these entities are well demon- The fracture line commonly extends from the jugular
strated using MDCT. foramen or foramen magnum to the middle cranial
fossa. It may pass through bony labyrinth and may
Problem-Solving Tool/Cases in Head destroy both vestibular and cochlear apparatuses. If it is
a bit more medial, it may transect the internal auditory
and Neck Imaging
meatus and the cochlear nerve within it. A transverse
Figures 1-55 through 1-57 illustrate other typical appli- fracture commonly results in sensorineural hearing
cations of MDCT for evaluation of inner ear pathology. loss. Over years, an old fracture may result in ossified
Figure 1-55 shows the case of a 10-year-old girl with labyrinth (which can be demonstrated with MDCT),
sensorineural hearing loss. A temporal bone CT scan severe vertigo, and nystagmus. It also can cause tran-
without contrast illustrates a complex left inner ear dys- section of the vestibule, vestibular nerve, or vestibular
plasia with aplasia of the left cochlea. Other congeni- aqueduct. These fractures are sometimes hard to detect
tal malformations are equally well illustrated by MDCT on axial MDCT images, requiring the Stenvers or Pöschl
(Figures 1-56 and 1-57). plane for detection. A perilymph fistula, cerebrospinal
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 35

SECTION I
A B

Figure 1-46 A: Sagittal recon-

structed multidetector computed
tomographic (MDCT) image show-
ing a unilateral locked facet at the
C5–6 level (arrow). B: Surface-
rendered image showing a different
view of a perched (locked) facet.
Thoracic perched facet at T10–11
shown in sagittal MDCT section
C (C) and focal magnified image at
D the T10–11 level (D).

fluid level in the middle ear, and fluctuating sensori- a new type of CT scanner based on flat-panel detector
neural hearing loss are other signs of occult trauma to technology. These scanners, called flat-panel volume CT
the inner ear. (fpVCT) scanners, are characterized by very high spatial
The otic capsule is the densest bone in the body. CT is resolution and volumetric coverage. They are described
quite sensitive in depicting mineralization (or lack there in detail later in this chapter. Some example images of
of) in the otic capsule and ossicles. Figure 1-59 shows temporal bone specimens acquired from one such pro-
a case of tympanosclerosis in a middle-aged man. This totype scanner are shown here.
pathology may be asymptomatic or may present as con- Figure 1-60 shows a reformatted fpVCT view of the
ductive hearing loss, often as a sequela of chronic otitis branching of the eighth cranial nerve into its vestibu-
media. lar part (white arrowhead) and the cochlear part (black
Tympanosclerosis may cause restriction of ossicular arrowhead). Its branches (small black arrowhead) can
movement and may involve the tympanic membrane, be followed through the modiolus to the bony spi-
suspensory ligaments, and tendon degeneration. Sec- ral lamina in the cochlea. The tensor tympani muscle
ondary stapes fixation due to oval window annular liga- (black arrow) in its canal next to the carotid (cross) and
ment involvement is not uncommon. Of these changes, the facial nerve canal (white arrow) next to the middle
only the bony changes are well visualized using CT. ear also are visible.
Demineralization of the otic capsule from otospongio- Figure 1-61 shows multiple segments of the facial
sis or otosclerosis is also well depicted by MDCT. nerve (small black arrowheads) in another reformatted
Visualization of the temporal bone structures is image obtained from the fpVCT volumetric data. These
crucially dependent on spatial resolution. Impressive structures are not as well seen on the MDCT or MRI
temporal bone images have been demonstrated using images due to their limited resolution. The ­reformation
36 Section I  Advanced Modalities: Protocols and Optimization

Figure 1-47 Coronal sections from com-

puted tomographic myelogram of cervical
spine rendered with minimum intensity
projection (MIP) showing posttraumatic
saccular outpouching of contrast at the C6–
7 and C7–T1 levels (white arrows) represent-
ing pseudomeningoceles along the right C7
and C8 nerve root sleeves. MIP brings out
the nerve roots embedded within the con- A B
trast-enhanced cerebrospinal fluid.

plane in Figure 1-61A is close to a horizontal section. It of the facial nerve (greater petrosal nerve) can be seen.
shows the facial nerve leaving the internal auditory canal The tensor tympani muscle (pinkish purple) is in the
(black arrow) through its canal (large black arrowhead) right half of the image; the stapedius muscle (also pink-
into the geniculate ganglion (large white arrowhead). ish purple) can be found in the left half. The stapedius
The image plane in Figure 1-61B is situated midway nerve (purple) innervating the stapedius muscle and the
between the sagittal and frontal planes. It shows both vestibulocochlear nerve (dark lilac) are depicted.
the tympanic segment and the descending mastoid The ability to render high-quality surface views opens
segment of the facial nerve. Note that the nerve in the a unique possibility in the evaluation of temporal bone.
canal is directly imaged in this specimen because air has “Virtual endoscopy” of the middle and inner ear can
dissected into this space during specimen ­preparation. be performed by positioning a camera in the temporal
Only a thin bony lamina separates it from the middle bone and prescribing an orientation and motion path.
ear (white arrow). The canal of the greater petrosal nerve Figure 1-65 shows three snapshots from a virtual endos-
(long white arrow) can also be seen. Due to a high jugu- copy movie generated using surface-rendered images
lar bulb (white star), only a thin bony lamina (small from fpVCT data. In Figure 1-65A, the virtual endo-
white arrowhead) separates the jugular vein from the scope is positioned in the external acoustic meatus,
middle ear cavity. The tensor tympani muscle (black close to the plane of the tympanic membrane, and is
star) can be found parallel to the eustachian tube. Figure facing medially. The tympanic membrane is removed by
1-62 shows another high-resolution dataset in which rendering its opacity level to zero (i.e., making it com-
the entire length of the cochlear aqueduct, a structure pletely transparent). Its position can be deduced from
not normally demonstrated by MDCT, can be seen. the handle of the malleus (black star) and the tympanic
The image quality and resolution of fpVCT are sulcus (small black arrows) where the circumference of
adequate for high-quality segmentation and volume the tympanic membrane is attached. The eustachian
rendering. Figure 1-63 shows a comparison of the tube (white star), long process of the incus (short white
volume-rendered views from MDCT and fpVCT. The arrow), and promontory (black cross) with its round
definition and detail of the high-contrast structures are window niche (white long arrowhead) are shown.
superior on the fpVCT images. This concept can be taken Behind the tendon of the stapedius muscle (large black
a step further by making 3-D models of the inner and arrowhead), the posterior crus of stapes is visible. In the
middle ear structures. Figure 1-64 shows one such 3-D right lower corner of the image can be seen the bulge
model of the right temporal bone seen from the antero- of a high jugular bulb, which is only partially covered
lateral direction. This model was built by individually by a thin bony lamina. Spaces that are covered only by
segmenting out anatomic structures from the fpVCT soft tissue (small arrowheads) make it a dehiscent high
image stack. In the foreground, the tympanic membrane jugular bulb. In Figure 1-65B, the camera is positioned
(yellowish green), malleus (orange), and incus (green) in the distal end of the eustachian tube. It is oriented
can be seen; the stapes (blue) is partially covered. The so that the viewing direction is about 45 degrees later-
facial nerve (purple) can be followed from behind the ally and posteriorly. The external auditory canal is vis-
bony labyrinth (transparent yellow) to its tympanic ible in the right half of the image. Besides the features
part. In front of the transparent bony cochlea, in which described in Figure 1-65A, the anterior crus of stapes
the spiral osseus lamina (brown) is visible, one branch can be seen (small black arrowhead). In Figure 1-65C,
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 37

SECTION I
A B C

D E
Figure 1-48 A: Plain radiograph of the thoracolumbar spine showing a complex kyphoscoliotic deformity. Straight sagittal and coronal refor-
mations (B, D) and curved sagittal and coronal reformations (C, E) from a computed tomographic myelogram. The curved reformatted images
give excellent details regarding multiple levels of thecal sac despite the extensive kyphoscoliotic deformity.

A B C
Figure 1-49 Postoperative imaging after laminectomy at L5 with transpedicular fixation at the L5–S1 level. Sagittal (A), coronal reconstruction
(B), and axial section (C) at the L5–S1 level demonstrating grade 2 spondylolisthesis of L5 over S1 with impingement of the right S1 nerve root
(white arrow) between the right-sided screw and the bony margin of the neural foramen.
38 Section I  Advanced Modalities: Protocols and Optimization

A B
Figure 1-50 Fifty-year-old woman who presented with subacute paraplegia and loss of sensations. (A) T2 weighted sagittal section through
midthoracic region showing partial collapse of the vertebrae adjoining destroyed disc, no obvious epidural abscess but canal narrowing and cord
hyperintensity suggesting cord edema. (B) Multidetector computed tomography with sagittal reconstruction showing the extent of vertebral body
destruction, disc destruction, and prevertebral necrotic collection in continuity with osseous disease. A minimally sclerotic component (white
arrow) protruding into the spinal canal indenting on the cord at this midthoracic level is also demonstrated by multidetector computed tomogra-
phy and likely is responsible for the patient’s symptoms.

Figure 1-51 Soft tissue and bone kernel axial sections of a 10-year-old boy with back pain and right-sided hip and knee pain. Computed
tomography showing permeative necrosis of the right pedicle and transverse process with a soft tissue component extending into the right quadra-
tus lumborum and erector spinae muscles with minimal epidural component. With these imaging characteristics, the differential considerations
would include Ewing sarcoma, lymphoma, and eosinophilic granuloma. Histopathology showed this lesion to be an anaplastic lymphoma.
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 39

SECTION I
Figure 1-52 Sagittal reformation through
the cervical spine and axial section at the
C1–2 level showing multiple well-defined
lytic lesions in the vertebral bodies with
collapse of C3 and a soft tissue component
arising from the left anterior arch of C1. The
posterior elements are relatively uninvolved.
These multidetector computed tomographic
features are suggestive of multiple myeloma.

Figure 1-53 Single slice from a stack of images along the Pöschl plane showing a nondehiscent superior semicircular canal.

Figure 1-54 Dehiscence of superior semicircular canal.

40 Section I  Advanced Modalities: Protocols and Optimization

the camera is positioned beneath the ossicular chain soft tissues of the orbit. CT also detects calcifications eas-
and is facing superiorly. Both crura of the stapes can be ily, a fact that is useful in characterizing an orbital mass.
clearly assessed. In addition to the features described CT scan is quick and generally motion free, and, in most
in Figures 1-65A and 1-65B, the short process of the cases, sedation is not required for pediatric patients.
incus within the tympanic attic is marked (long white The optimal protocol for MDCT of the orbit must
arrow). In all of these views, the chorda tympani and include thin axial slices, approximately 1.5 mm thick,
the tympanic membrane are not visible because their reconstructed using bone and soft tissue kernels. From
CT numbers were below the threshold used for surface these routine axial CT slices, it is customary to obtain
rendering. sagittal and coronal sections. In complex cases, oblique
sagittal sections also should be obtained (Figure 1-66).
If an orbital mass, infection, or inflammatory condition
Orbital Pathologies
is suspected, IV contrast must be administered. Noncon-
Orbital pathologies can be broadly divided into trau- trast examination may be sufficient for follow-up cases.
matic, congenital, vascular/lymphatic, infectious, inflam-
matory/metabolic, and neoplastic categories. All of these Orbital Trauma
entities are well demonstrated by MDCT, making CT scan
the first-line imaging modality for most orbital pathol- The choice of CT after blunt or penetrating trauma to
ogy. CT is most valuable in delineating the shape, size, the orbit, globe, or face is obvious. It can show fractures,
location, and characteristics of orbital lesions. It also can hemorrhage, soft tissue swelling, embedded foreign
guide clinicians during surgical interventions because it bodies, and other derangements of the orbit in exqui-
places a lesion with respect to the various spaces of the site detail, even in an uncooperative patient. Figure 1-67
orbit. This subsection briefly illustrates some example shows two cases of trauma resulting in lens dislocation.
cases of orbital pathologies that demonstrate the utility In the second case, the lens has been displaced from the
of MDCT. anterior portion of the globe and has come to rest in
Signs and symptoms of orbital disease that prompt a the dependent portion of the vitreous humor. Although
CT scan include exophthalmos (unilateral or bilateral), trauma is the most common cause of lens subluxation,
displacement of globe, ptosis, diplopia, limitations of other causes include Marfan syndrome, Ehlers-Danlos
extraocular motility, decreased vision, visualization or syndrome, Weill-Marchesani syndrome, familial ectopia
palpation of an orbital mass, swelling, orbital pain, lentis, homocystinuria, cataract surgery, and aniridia.
abnormal vascularity, and trauma. Although the clini-
cian may have a good sense of the state of the superficial Inflammatory and Metabolic
aspects of the eye and the globe, evaluation of the retro-
Conditions
bulbar areas requires a tomographic modality.
The advantages of MDCT in the evaluation of tempo- Inflammatory and metabolic conditions form a hetero-
ral bone also apply to orbital pathologies. There is natu- geneous group that includes idiopathic orbital inflam-
ral contrast between the retrobulbar fat, bone, air, and matory disease (more commonly referred to as orbital

Figure 1-55 Axial sections through the posterior fossa, reconstructed with bone kernel, showing absence of the left internal auditory canal.
The semicircular canals protrude into the cerebropontine angle, and the left-sided cochlear turns are aplastic.
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 41

pseudotumor), optic neuritis, thyroid-associated orbitop- lid ­swelling, conjunctival injection and edema, motil-

SECTION I
athy, and a variety of granulomatous diseases, such as ity restrictions, ptosis, and increased orbital pres-
Wegener granulomatosis, tuberculosis, and ­sarcoidosis. sure. Orbital pseudotumor may be acute, subacute,
All of these conditions of the orbit are well demon- or chronic. It may present as a single episode, it may
strated by MDCT. To illustrate the role of MDCT in the be continuous, or it may be intermittent. The chronic
management of these conditions, orbital pseudotumor form may evolve from the acute or subacute variety, or
is examined in detail. it may begin as a chronic process. The chronic form
Idiopathic inflammatory orbital pseudotumor is the represents the sclerosing type. MDCT is the primary
third most common orbital disease after Graves dis- investigative modality; MRI is reserved for evaluation
ease and lymphoproliferative disease. It may involve of extraorbital extension.
the orbit, lungs, and other systems. Orbital and perior- Orbital pseudotumor is diagnosed using a combina-
bital pain is common during acute onset. Other clini- tion of clinical findings, MDCT findings, and response to
cal signs and symptoms may include ­exophthalmos, steroid therapy. Although MDCT provides useful infor-
mation, the ultimate diagnosis is clinical. Fine-needle
aspiration biopsy with CT guidance can be used when
questions arise. For example, CT-guided biopsy may be
necessary when the pseudotumor is mass-like, does not
respond to steroid therapy, or is a sclerosing type.
Based on its radiologic appearance, pseudotumor
can be classified as dacryoadenitis, diffuse orbital infil-
tration, myositis, orbital mass, sclero-uveitis, perineu-
ritis, or eyelid pseudotumor. Combinations of these
pathologic patterns are possible. Although many of
these conditions are evaluated during a comprehensive
eye examination, MDCT plays a crucial role in the eval-
uation of retrobulbar disease. For example, CT locates
the enlargement of the lacrimal gland in dacryoadeni-
tis. Myositis typically presents as pain during extraoc-
ular muscle motion but cannot be directly evaluated
clinically. CT scan readily shows tubular, irregular,
asymmetric enlargement of the involved extraocular
muscles (Figure 1-68). The tendons of the affected
muscles also are enlarged and broadened in this con-
dition, a key point that differentiates it from Graves
ophthalmopathy. Lateral rectus is most ­commonly
affected; involvement of superior oblique and palpe-
bral muscles is rare.
Figure 1-56 Axial section through the right temporal bone using a
sharp bone kernel showing a well-defined canal (black arrow), superior
The appearance of pseudotumor on contrast-
and separate from the internal auditory canal, representing an anoma- enhanced MDCT scan is suggestive but nonspecific.
lous channel for the seventh cranial nerve. Differential diagnosis of orbital pseudotumor includes

A B
Figure 1-57 Undersegmented left cochlea with poorly formed interscalar septum representing a Mondini malformation.
42 Section I  Advanced Modalities: Protocols and Optimization

Figure 1-58 Axial sections through the right mastoid of a 31-year-old man who presented with altered mental status after sustaining a head
injury from a fall 3 days ago. The bone kernel shows the fracture line perpendicular to the petrous ridge extending through the tympanic portion
of the seventh nerve and lateral semicircular canal.

Figure 1-59 Tympanosclerosis involving the ossicles.

 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 43

Graves ophthalmopathy, infections (bacterial, granu- compressive optic neuropathy. Superior, medial, and

SECTION I
lomatous, fungal), other granulomatous conditions inferior recti are more preferentially involved, and the
(Wegener granulomatosis, sarcoidosis), metastatic dis- involvement is predominantly bilateral (90%) and sym-
ease (typically breast, lung), amyloid infiltration, histio- metric (70%). Isolated involvement of a single extraocu-
cytosis (primarily in children), and rare entities such as lar muscle is uncommon (~5%). CT scan may show fat
Erdheim-Chester disease. expansion and enlargement of the extraocular muscles
Thyroid-associated ophthalmopathy or Graves dis- with more than normal enhancement. Increased orbital
ease presents with eyelid retraction, exophthalmos with fat may secondarily compress nerves. Figure 1-69 shows
bilateral enlargement of the extraocular muscles, and two cases of thyroid ophthalmopathy.

Periorbital and Orbital Infections

Infections of the obit may result in orbital cellulitis and
abscess formation. Orbital infections may be viral, bac-
terial, or fungal (typically, aspergillus or mucormyco-
sis). Contrast-enhanced MDCT is a reliable modality for
assessing orbital infections that require further workup.
The rapidity of this test and its wide availability make
MDCT the first-line imaging modality for evaluation
of infections. The orbital septum is a key landmark in
assessment of periorbital/orbital infections. It is a fas-
cia arising from the periosteum of orbital margin and
inserts into the aponeurosis and fascia of the upper and
lower eyelids at the margins of the superior and ­inferior
tarsal plates. The orbital septum defines the margin
between the preseptal and postseptal compartments.

Problem-Solving Tool/Cases in
Orbital Lesions
MDCT can readily distinguish preseptal from postsep-
tal cellulitis. This is an important distinction because
a preseptal cellulitis can be managed conservatively,
Figure 1-60 Reformatted flat-panel volume computed tomo- whereas a postseptal extension of infection is a poten-
graphic view of branching of the eighth cranial nerve into its vestibu- tial emergency. CT should be considered in all cases
lar part (white arrowhead) and cochlear part (black arrowhead). Small
black arrowhead, Modiolus; black arrow, tensor tympani muscle; cross,
where severe eyelid swelling obstructs the clinician’s
carotid; white arrow, facial nerve canal. (Courtesy of Dr. Soenke Bar- ability to properly examine the globe. Clinically, pre-
tling, DKFZ, Heidelberg, Germany) septal cellulitis presents with erythema and swelling of

Figure 1-61 Multiple segments of the facial nerve (small black arrowheads) in reformatted images from a flat-panel volume computed tomogra-
phy dataset. A: axial reformat and B: coronal reformat. Tympanic and descending mastoid segments of the facial nerve (black arrow heads). Black
arrow, Internal auditory canal; large white arrowhead, geniculate ganglion; white arrow, thin bony lamina separating tympanic segment from middle
ear; long white arrow, canal of greater petrosal nerve; white star, high jugular bulb; small white arrowhead, thin bony lamina separating jugular vein
from middle ear cavity; black star, tensor tympani muscle. (Courtesy of Dr. Soenke Bartling, DKFZ, Heidelberg, Germany)
44 Section I  Advanced Modalities: Protocols and Optimization

A B

C D
Figure 1-62 Reformatted flat-panel volume computed tomo- Figure 1-63 Volume-rendered views of the ossicular chain by mul-
graphic image through the base turn of the cochlea showing the entire tidetector computed tomography (A, C) and flat-panel volume com-
length of the cochlear aqueduct, a feature that is generally not seen puted tomography (fpVCT) (B, D) from inferior (A, B) and posterior
on routine multidetector computed tomographic images. (Courtesy (C, D) views. The volume-rendering transfer function is separately
of Dr. Soenke Bartling, DKFZ, Heidelberg, Germany) optimized for both datasets after the ossicular chain was segmented
out of the volumes. The structure of the ossicular chain is much bet-
ter visualized using fpVCT. (Courtesy of Dr. Soenke Bartling, DKFZ,
Heidelberg, Germany)

Figure 1-64 Three-dimensional model of the right temporal

bone seen from the anterolateral direction. Color code: tympanic
­membrane—yellowish green; malleus—orange; incus—green; stapes—
blue; facial nerve—purple; bony labyrinth—transparent yellow; trans-
parent bony cochlea with osseus lamina spiralis—brown; tensor
tympani muscle—pinkish purple structure in right half of image; stapedius
muscle—pinkish purple in left half of image; stapedius nerve—purple
structure inserting in stapedius muscle; vestibulocochlear nerve—dark
lilac. (Courtesy of Dr. Soenke Bartling, DKFZ, Heidelberg, Germany)
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 45

SECTION I
+
+

*
* +

A B C
Figure 1-65 Three surface-rendered views from virtual endoscopy movie from flat-panel volume computed tomography dataset. A: Camera
is positioned in external acoustic meatus and is facing medially through the tympanic membrane, which has been removed. Black star, Handle
of malleus; small black arrows, tympanic sulcus; white star, eustachian tube; short white arrow, long process of incus; black cross, promontory; long
white arrowhead, round window niche; large black arrowhead, tendon of stapedius muscle; small (white) arrowheads, dehiscent high jugular bulb.
B: Camera is positioned in distal end of eustachian tube and is facing the middle ear cavity. Small black arrowhead, Anterior crus of stapes. C: Vir-
tual endoscope is positioned beneath the ossicular chain and is facing superiorly. Long white arrow, Short process of incus within tympanic attic.
(Courtesy of Dr. Soenke Bartling, DKFZ, Heidelberg, Germany)

the eyelid without any proptosis, chemosis, or pupillary blindness, intracranial abscess, and even death. MDCT
defect (Figure 1-70). MDCT may show streaky density in orbital cellulitis demonstrates fat stranding and
within the fat anterior to the orbital septum, often sec- other inflammatory changes in the retrobulbar orbital
ondary to superficial facial infection. Because of a valve- fat. These streaky densities within orbital fat may indi-
less venous plexus, extension posterior to the orbital cate spread of infection through the venous system or
septum is a dreaded complication. Preseptal cellulitis ­periorbita.
usually is not sinogenic, and the paranasal sinuses usu- Advanced cases of infection may result in a subperi-
ally are clear. osteal abscess from bacterial infection extending from
Clinical findings of postseptal cellulitis, also known the retrobulbar fat or, more commonly, from the sinuses
as orbital cellulitis, include proptosis, chemosis, restric- through the cortical bone. A subperiosteal abscess, if it
tion of ocular motility, and papillary defect. Evaluation is sinogenic, may or may not involve the orbital fat. In
of the orbit and sinuses by CT becomes essential in these all cases, there is central displacement of the adjacent
cases to confirm the diagnosis and to assess the extent of rectus muscle. All complications of orbital infections are
infection. Delayed treatment in such cases may lead to well demonstrated by MDCT. They include fat strand-
ing, proptosis, orbital phlegmon, abscess, cavernous
sinus thrombosis, and superior orbital vein thrombo-
sis. Figures 1-71 and 1-72 demonstrate two cases of sub-
periosteal abscess formation. In Figure 1-72, the abscess
involves the superior portion of the orbit. Although CT
is excellent at demonstrating the orbital extension of
the abscess, the intracranial extension may be difficult
to elucidate using MDCT.
Besides infection, other conditions involving the
sinuses may result in orbital pathology. Figure 1-73
shows an example. MDCT demonstrates orbital asym-
metry and spontaneous enophthalmos caused by sinus
atelectasis in a condition called silent sinus syndrome.
This condition is a result of acquired obstruction of the
maxillary sinus ostium leading to sinus hypoventila-
tion and accumulation of sinus secretions. Over time,
resorption of sinus secretions generates subatmospheric
pressure in the maxillary antrum. This causes maxillary
sinus collapse, with prolapse of the walls of the sinus.
The floor of the orbit formed by the orbital plate of the
maxillary bone is relatively thin and gives in easily. This
process can be considered the reverse of that occurring
in an orbital blowout fracture: the orbital contents are
Figure 1-66 Angulation of oblique sagittal sections (A) and repre- being pulled into the maxillary sinus as opposed to
sentative oblique sagittal section through the orbit (B). being pushed into it.
46 Section I  Advanced Modalities: Protocols and Optimization

Figure 1-67 Two cases of lens dislocation. A: Thirteen-year-old after trauma to right eye. B: Patient with unilateral trauma to left eye.

Congenital Conditions Vascular and Lymphatic

Malformations
Most congenital orbital pathologies are readily demon-
strated by MDCT. These conditions include entities such Vascular and lymphatic malformations of the orbit,
as neurofibromatosis type 1 (NF1), persistent hyperplas- which form a continuum with varying proportions
tic primary vitreous, microphthalmos, coloboma, Coats of arterial, lymphatic, and venous elements, include
disease, dermoids, and epidermoids. NF1 is considered ­entities such as capillary and cavernous hemangiomas,
here as a representative example. lymphangiomas, and venous varices. Pathologically,
Figure 1-74 shows a case of NF1 with orbital involve- these malformations have elements of lymphatic, arte-
ment. A plexiform neurofibroma anywhere within the rial, and venous tissue.
body is pathognomonic for NF1 and is quite common in Venous lymphatic malformations arise from a plu-
the orbit. Typically, the involvement is unilateral, as it is ripotent venous analogue that develops into both
in this case. CT scan shows serpentine masses in the retro- venous and lymphatic structures that do not have any
bulbar area representing plexiform neurofibromas. These connection to systemic venous or lymphatic structures.
masses may involve intraorbital nerves, muscles, optic They enlarge slowly, producing progressive proptosis.
nerve sheath, or sclera. Other cranial nerves also may be Many manifest abruptly because of hemorrhage after
involved and may result in expansion of the associated minor trauma or infection. Sometimes, no antecedent
foramina at the skull base. Associated sphenoid dysplasia cause is identified, and hemorrhage may be spontane-
is common. These plexiform neurofibromas in NF1 gradu- ous. Lymphangiomas are associated with intracranial
ally enlarge until they involve nearly all orbital structures, developmental venous anomalies, sinus pericranii, and
both internal and external. The differential diagnosis of AVMs. Figure 1-75 shows the CT scan of a 6-year-old
these lesions includes other infiltrating orbital lesions, with an orbital lymphangioma. Generally, these masses
such as capillary hemangioma, rhabdomyosarcoma, his- are poorly marginated and lobulated, and show irregu-
tiocytosis, lymphoma, leukemia, and metastases. lar enhancement.
Lymphangiomas show irregular enhancement, but
a lobulated, irregular orbital mass that shows intense
enhancement in an infant likely is a capillary hemangi-
oma. It may involve any part of the orbit. On noncontrast
CT it is slightly hyperdense and turns homogeneously
bright on postcontrast images. A rhabdomyosarcoma
can have a similar appearance, except that it usually is
invasive and shows bone destruction, especially at large
sizes. Neuroblastoma and hematopoietic malignancies
are other entities in the differential consideration.

Orbital Masses and Neoplastic

Conditions
Congenital orbital tumors include hamartomas (e.g.,
capillary hemangiomas, neurofibromatosis) and choris-
tomas (e.g., dermoids, epidermoids, lipodermoids).
Capillary hemangiomas of the orbit are benign
tumors commonly seen in the pediatric age group,
whereas cavernous hemangiomas of the orbit are more
Figure 1-68 Orbital myositis involving the left medial rectus muscle. common in adults. Diagnosis is mostly established
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 47

SECTION I
Figure 1-69 Thyroid ophthalmopathy secondary to Graves disease. A: Axial section showing extensive involvement of medial rectus muscles
resulting in bowing of left optic nerve. B, C: Coronal and axial sections from contrast-enhanced computed tomographic scan showing bilaterally
symmetric enlargement of superior, medial, and inferior rectus muscles. The lateral rectus muscles are relatively spared.

by CT, but MRI may play a role. Lymphangiomas can 1-76. The mass on the left is hyperdense compared
occur in the conjunctiva, eyelids, orbit, oropharynx, or with the normal vitreous humor, occupies a normal-
sinuses. CT scan with contrast is useful for locating these sized globe, and is devoid of any calcifications. A key
lesions. Optic nerve sheath meningiomas, optic nerve differentiating feature of the mass on the right is the
gliomas, and neurofibromas are the neural tumors for presence of punctuate and finely speckled calcifica-
which CT plays a role in detection. Malignant tumors tions. On postcontrast images, this mass shows mod-
of the orbit include retinoblastoma, ocular melanoma, erate enhancement. This pattern of calcifications and
optic pathway glioma, adenoid cystic carcinoma of the enhancement is characteristic of a retinoblastoma. The
lacrimal gland, and lymphoma. MDCT can be used in hyperdense, noncalcified mass on the right represents
both detecting and managing these lesions. CT also is an exudative retinopathy of Coats disease. As shown
helpful in evaluating the lesions of the lacrimal gland in Figure 1-77, MDCT also readily demonstrates the
to differentiate between inflammatory and neoplastic extent of the mass, its bony involvement, and any
conditions. spread to the adjacent compartments. This case shows
Contrast-enhanced CT scan can effectively dem- a bladder cancer metastasis that has invaded through
onstrate these orbital masses and show characteristics the superior orbital foramen to involve the intracranial
that can narrow the differential. Although the soft tis- compartment.
sue contrast of MRI is superior in demonstrating these
pathologies, CT shows calcifications and the relation- MDCT FOR CERVICAL MASSES
ship to adjacent bony and vascular structures to better
AND INFECTIONS
advantage.
For example, consider the two soft tissue masses in MDCT is an indispensible tool in the evaluation of a
the posterior aspect of the left globe shown in Figure variety of cervical masses and infectious conditions. This
section presents several examples that demonstrate the
utility of MDCT for cervical masses and infections.
MDCT shows bone destruction, thinning, and inva-
sion to better advantage than does MRI. These changes
can be reliably distinguished from simple remodeling of
the bone from a chronic, nonaggressive expansile pro-
cess. In this case, MRI scan did not really narrow the
differential and was not as useful at MDCT scan.
Figure 1-78 shows the case of an 18-year-old man
with history of choroid plexus papilloma resected at
age 1 year, who presented with increasing nasal conges-
tion. MDCT with contrast demonstrates an aggressive
nasal mass that is destroying the adjacent bone. The
lamina papyracea and the ethmoid air cells on the right
are destroyed, with bowing of the medial rectus. This
imaging presentation is consistent with a fast-growing
malignancy. Pathology study proved this mass to be an
alveolar-type rhabdomyosarcoma.
Figure 1-79 shows axial section and coronal and sagit-
Figure 1-70 Case of superficial infection resulting in preseptal cel- tal reconstructed images from contrast-enhanced MDCT
lulitis. The retrobulbar fat is free of any signs of infection. of the face and brain of a young male who presented
48 Section I  Advanced Modalities: Protocols and Optimization

Figure 1-71 Four-year-old girl with 2-day history

of fever and acute onset of right eye swelling. A sino-
genic subperiosteal abscess that is continuous with an
opacified ethmoid air cell through a dehiscence in the
lamina papyracea, with resulting central deviation of
the medial rectus muscle, can be seen.

Figure 1-72 Case of orbital cellulitis and subperiosteal abscess formation.

Figure 1-73 Forty-year-old patient with diplopia who presented with a feeling of “sinking of the eye.” Atelectasis of left maxillary sinus with
resultant enophthalmos can be seen on axial and coronal sections. (Images courtesy Dr. Michelle Rottblatt.)
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 49

SECTION I
Figure 1-74 Ten-year-old patient with proptosis of the left globe. Noncontrast computed tomography (left) demonstrating hypodense infiltra-
tive soft tissue masses representing plexiform neurofibroma that enhance on postcontrast image (right). Bony changes and proptosis are seen.
Both the superior orbital fissure and the optic canal are enlarged.

the overall extent of this mass—features that are well

demonstrated by MDCT—characterize it as a juvenile
nasopharyngeal angiofibroma.
MDCT is the modality of choice for demonstrating
the internal vascularity and relationship of a mass to
adjacent vascular structures. A carotid body tumor is
a case in point (Figure 1-80). This tumor, also known
as intercarotid paraganglioma, glomus tumor, or chemo-
dectoma, is a neural crest derivative that occurs at the
carotid bifurcation. It is a slowly growing, hypervascu-
lar, intensely enhancing, compressible mass that is fixed
vertically by the carotid bifurcation but can move lat-
erally. It characteristically splays the carotid bifurcation
and may encase vessels. Its ovoid shape is best seen with
sagittal and coronal MDCT images (Figure 1-80).
MDCT is ideal for demonstrating displacement of
the adjacent structures and fascial layers. For example,
masses in the carotid sheath displace the fat in the para-
pharyngeal space anteromedially. Neurogenic tumors,
such as those arising from the vagus nerve or the sympa-
thetic chain, cause anterior displacement of the carotid.
In general, vagal lesions cause anteromedial displace-
Figure 1-75 Six-year-old patient with orbital proptosis. Noncon- ment of the carotid because the vagus nerve is situated
trast computed tomographic scan (not shown here) demonstrated posterior to the carotid. Sympathetic chain schwanno-
multicystic hypodense mass and remodeling of bone. Variable wall mas are located at the posteromedial border of the ICA
enhancement is seen on postcontrast images. Mass effect on the poste- and typically result in anterior or anterolateral displace-
rior globe can be appreciated. ment of the carotid. If posterior displacement of the
carotid artery is observed, the differential considerations
should include lesion arising from the deep lobe of the
with epistaxis. The images show an avidly enhancing parotid or from the prestyloid parapharyngeal space.
mass in the right pterygomaxillary fissure extending into Several examples of infectious conditions as depicted
the sphenoid sinus, right infratemporal fossa, and pos- by MDCT have been shown. The key characteristics of
terior nasopharynx with deviation of the nasal septum this modality that make it suitable for imaging those
to the left of midline. Marked neovascularity, character- sites make it equally applicable for evaluation of head
istic location within the pterygomaxillary fissure, and and neck infections. Figure 1-81 shows the case of an
50 Section I  Advanced Modalities: Protocols and Optimization

Figure 1-76 Two different soft tissue masses in the posterior aspect of the left globe representing Coats disease (left) and retinoblastoma (right).

Figure 1-77 Fifty-year-old patient

with a history of bladder cancer
who presented with right eye pain.
Contrast-enhanced multidetector
computed tomography showing
an enhancing mass in the posterior
aspect of the orbit that has spread to
the intracranial compartment via the
superior orbital foramen.

Figure 1-78 Case of rhabdomyosarcoma (alveolar type).

 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 51

man with human immunodeficiency virus and acquired

SECTION I
immunodeficiency syndrome, presented with a 12-day
history of left neck pain, fever, headaches, ­nausea, and
vomiting. CT scan of the chest, head, and neck with con-
trast showed a focal, hypoattenuating mass in the left
neck, with irregular margins and peripheral enhance-
ment. The sternocleidomastoid muscle is swollen, as are
the surrounding subcutaneous soft tissues. The thyroid,
trachea, and carotid artery are deviated to the right, and
the internal jugular vein (IJV) is thrombosed. Differ-
ential considerations for IJV thrombophlebitis include
tumor thrombus, lymphoma, otitis media or externa,
recent IJV catheterization, and Lemierre syndrome. This
case is a classic presentation of Lemierre syndrome.
Patients with this syndrome generally are young with
pharyngitis or peritonsillar abscess who present with
high fever, rigors, cervical adenopathy, and tenderness.
Thrombophlebitis of IJV develops, and distant abscess
formation from metastasis is common. Distant septic
metastases most commonly involve the lungs and cause
pulmonary infiltrates, pleural effusions, and cavita-
tions. Joint infections and hepatic or splenic abscesses
also may develop. Early treatment with antibiotics is
essential.
MDCT is a quick and easy way to show the location
and extent of disease by demonstrating the associated
inflammatory changes, enhancement, and fluid dis-
secting in different fascial layers. Rim-enhancing col-
lections, necrotic lymph nodes, and cystic structures
(Figure 1-83) are well demonstrated by MDCT.

MDCT: STATE OF THE ART

AND FUTURE TRENDS
Figure 1-84 illustrates a simplified timeline summa-
rizing the key increments in the capabilities of CT.
The evolution of MDCT was made possible by steady
improvements in spatial, contrast, and temporal reso-
lution. These, in turn, were the result of continuous
engineering advancements in detector design, gantry
rotation speed, slip-ring technology, and axial coverage
of the detectors. The state of the art of MDCT is summa-
rized here in terms of these key benchmarks, followed
by some new and exciting innovations in technology
that have recently become available.
Figure 1-79 Highly vascular mass involving multiple compart-
ments that proved to be juvenile nasopharyngeal angiofibroma at
pathology. State of the Art in MDCT
Spatial Resolution
Detector technology has perhaps seen the most radi-
11-month-old girl with a retropharyngeal abscess sec- cal changes in CT engineering. The current detectors
ondary to trauma to the oropharynx from a drum stick. are solid state and offer a resolution of about 0.4 mm
The image clearly shows the abscess with foci of gas in-plane and 0.5 mm along the Z-direction. The num-
within it. Also seen is a hypodense track from the oro- ber of detector rows has steadily increased, and 64-slice
pharyngeal mucosa down to the abscess cavity, likely detectors currently are the norm. Scanners with as many
representing the traumatic penetration of the foreign as 320 slices have been introduced recently into clini-
body. The relationship of the abscess with the adjacent cal practice. The available detectors can be configured in
carotid artery and jugular vein is clearly demonstrated in many arrangements, offering a wide variety of settings
this image, as is the fact that they are not thrombosed, a for collimation, pitch, and slice thickness.
dreaded complication of head and neck infections. Although traditional MDCT scanners have signifi-
A case of cervical infection leading to thrombophle- cantly improved spatial resolution, some of the very fine
bitis is shown in Figure 1-82. The patient, a 37-year-old structures in head and neck radiology are still beyond
52 Section I  Advanced Modalities: Protocols and Optimization

Figure 1-80 Axial and oblique

sagittal views of a carotid body
tumor.

their reach. For example, the footplate of the stapes, the especially those in temporal bone, are briefly described
attachment of the stapedius muscle, the spiral osseous later in this chapter under flat panel volume CT.
in the cochlea, and many other structures in the tem-
poral bone are more imagined than seen at the clinical Contrast Resolution
resolution available today. Recently, digital flat-panel Differentiation between gray matter and white matter,
­detector-based CT systems have been developed and a difference of about 10 HU in CT attenuation, is essen-
shown to provide isotropic spatial resolution of about tial for detection of acute infarctions. Quantification
130 μm. This innovative design, which provides unprec- of small changes in parenchymal opacification forms
edented visualization of small intracranial structures, the basis of perfusion imaging. At diagnostic energies
(70–150 kVp), such small differences in attenuation
can be subtle, and detection of these subtle differences
can be challenging in presence of noise, partial volume
effects, and motion artifacts. With the advent of highly
engineered solid-state detectors using rare earth crys-
talline materials, the detective quantum efficiency has
increased significantly. These advances, coupled with
newer acquisition and processing techniques, have
resulted in steady improvement in the contrast resolu-
tion of the scanners. Currently, single-energy, state-of-
the-art MDCT scanners can discriminate differences as
subtle as 1 HU. The discriminating power of a scanner
can be further augmented using dual-energy scanning, a
topic that is further discussed later in this chapter under
dual-source and dual-energy CT.

Temporal Resolution
Currently, CT imaging for most neurologic applications,
with the exception of perfusion imaging, is static. The
need for higher temporal resolution is primarily driven
by cardiac imaging. Nonetheless, neuroimaging also
benefits from faster scanners. Current MDCT systems
provide temporal resolution in the range from 165 to
330 ms depending on gantry speed and the reconstruc-
tion algorithm used (i.e., whether projection data from
180 or 360 degrees is used for reconstruction). With the
Figure 1-81 Eleven-month-old girl who presented with gagging
after trauma to the oropharynx from a drum stick. Multidetector com- advent of these fast scanners, imaging of a wide swath
puted tomography demonstrating a retropharyngeal abscess with foci of anatomy has become possible with one injection
of air within it. Adjacent carotid artery and jugular vein are patent. of contrast. For example, a head and neck CTA from
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 53

of a gantry rotation is sufficient for reconstructing a sin-

SECTION I
gle slice. The SOMATOM Definition (Siemens Medical
Solutions, Forchheim, Germany), a recently introduced
dual-source CT scanner, has a rotation time of 0.33 sec-
ond. Therefore, a temporal resolution of approximately
0.083 second is feasible. Such high temporal resolution
may prove beneficial in studying dynamic phenomena
such as neuroperfusion and cardiovascular events. High
temporal resolution also may prove useful in visualizing
processes such as early venous shunting in an AVM and
tumor vascularity.
Of note, with dual-source CT the radiation dose is
not increased by a factor of two. Although twice as much
power is being delivered per unit time, the scan takes
almost half as much time as compared to single source
MDCT scanners. Therefore, the overall effective dose is
the same as that with a conventional MDCT scanner. In
fact, for cardiac examinations that rely on oversampling
the projection data to account for ectopic beats, the
overall x-ray dose is decreased compared with a single-
source CT.
The two x-ray sources of a dual-source CT scanner
can be operated at two different tube voltages. This gives
rise to dual-energy CT, which is primarily used for tis-
sue characterization. Dual-energy CT is based on the
principle that x-ray attenuation is energy dependent.
The peak tube voltage (kVp) determines the average
energy of the x-ray beam. Therefore, a change in kVp
leads to an alteration of average photon energy. Because
the beam attenuation caused by different materials is
energy dependent, different tissue types can be discrimi-
nated by their attenuation characteristics at two differ-
ent energy levels.
The x-ray absorption depends on the atomic num-
ber and the density irrespective of chemical bonding.
For example, the high attenuation of iodine at low kVp
changes to half at high photon energies. In contrast, the
attenuation of bone changes much less when the kVp
of the tube is changed. Dual-energy CT uses this key
Figure 1-82 Axial and coronal multidetector computed tomogra- difference to distinguish between different materials.
phy of head and neck demonstrating postanginal sepsis and thrombo- Two x-ray sources perpendicular to each other, running
phlebitis of left internal jugular vein in Lemierre syndrome.
simultaneously at two different energy settings, acquire
two datasets using two separate detector arrays. These
datasets, at two different energy levels, are perfectly reg-
the aortic arch to the vertex can be completed in less istered with respect to each other as they are acquired
than 10 seconds. Temporal resolution can be further very close to each other in time.
enhanced by using two x-ray sources and two detectors The two datasets have different attenuation levels or
simultaneously. This quantum leap in CT technology is Hounsfield units for the same tissue. A weighted aver-
discussed next. age image of the two datasets is used to obtain a scan
with a cumulative dose from the two tubes. If the energy
levels for the two tubes are 80 and 140 kVp, the aver-
Dual-Source and Dual-Energy CT
age scan can be regarded as that obtained at 120 kVp.
Dual-source CT (DSCT) is a new innovation in CT tech- The real power of dual-energy CT is realized with the
nology. It uses two x-ray sources and two detectors in help of special software and postprocessing tools that
a single gantry to accelerate image acquisition. Using can analyze the two datasets to extract material specific
two imaging chains simultaneously effectively doubles differences in attenuation. These differences, in turn,
temporal resolution and x-ray tube power. In addition, enable ­classification of the chemical composition of the
the two imaging chains can be operated at different tube scanned tissue.
voltages, enabling dual-energy CT (discussed later in this The overall attenuation of any tissue is primarily
section). Because projection data from just over half of a determined by two main interactions: photoelectric
rotation is sufficient for image reconstruction, when the absorption and Compton scattering. For any material,
scanner is operated in the dual-source mode one quarter two unknown parameters weight the contributions of
54 Section I  Advanced Modalities: Protocols and Optimization

Figure 1-83 Bilateral level 2 well defined, peripherally enhancing cystic lesions (white arrow) representing lymphoepithelial cysts in human
immunodeficiency virus lymphadenitis.

Dual
source
CT
Innovations
in CT
Multi-
CT 2000 spectral
Multi-slice CT CT
16 64 Flat-
4
0.4 0.33 panel
The 90s 0.5s CT
Spiral CT Dual-
0.75s energy
2s 1s
The 80s CT
Axial CT
Portable
Lung Body CT
Head

1970 1990 1998 2008

Axial CT Spiral CT Multi-detector CT
Figure 1-84 Some key milestones in the evolution of multidetector
computed tomography.

these two interactions to the overall attenuation coef- within an image voxel can be estimated using dual-
ficient. Therefore, the total attenuation coefficient of a energy CT. The contribution to the overall attenuation
material can be decomposed into two parts that describe by these two substances is the desired estimate. For the
the contribution of these two interactions. Each compo- two-component model, imaging at two energy settings
nent is energy dependent; however, the energy depen- provides a solution because there are two unknowns.
dencies can be treated as known functions as they can be The mass fraction of each substance can be derived from
calibrated a priori. Dual-energy CT provides two mea- the measured weighting factors.
surements for each voxel from which the two unknown Dual-energy CT may offer clinically useful tissue sig-
parameters can be estimated. natures for different normal and pathologic conditions
In a two-component tissue model, each image voxel and currently is an area of active research. For exam-
is assumed to be composed of two known substances ple, dual-energy CT can distinguish between calcium
(e.g., iodine and calcium). The attenuation coefficients deposits and injected iodine. This property can be used
of these substances in their pure form are known at in CTA for automatic bone subtraction (Figure 1-85).
each kVp level. The fraction of these tissue types ­present Enhancement characteristics of different tissue types
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 55

SECTION I
A B
Figure 1-85 Dual-energy computed tomography enables bone subtraction for comprehensive evaluation of complex vascular structures.
(Images courtesy University of Munich-Grosshadern Campus, Munich, Germany.)

A B C
Figure 1-86 Dual-energy computed tomography. A: Noncontrast imaging showing a hyperdense intraparenchymal hemorrhage in the left
frontoparietal region. B: Contrast-enhanced image of the same patient. Any active contrast extravasation into the hematoma is difficult to see.
C: Iodine-only image obtained by processing the low and the high kVp images showing extravasation of iodine in the hematoma. Such active
extravasation may reflect a risk of hematoma expansion with time. (Images courtesy University of Munich-Grosshadern Campus, Munich,
­Germany.)

also may be better demonstrated using dual-energy calcific portions, making available a pure soft tissue
subtraction. image. Other applications, such as characterization
On a conventional MDCT scan, acute intracranial of kidney stones, differentiation of hard plaque from
hemorrhage and iodine extravasation appear radiodense. injected contrast, and detection of pulmonary perfusion
It is possible to separate the two using dual-energy CT. defect, have been reported in the literature.
Iodine extravasation in a hematoma after IV contrast Visualization of dual-energy scans poses a unique
injection may be a marker of hematoma expansion ­ display challenge because reviewing high-energy and
(Figure 1-86). Analogues of this phenomenon, called low-energy scans separately is not useful to a human
the spot sign, have been seen on routine MDCT of the operator. With dual-energy CT, the attenuation caused
brain. by iodine can be subtracted out. Therefore, a virtual
Visualization of soft atherosclerotic plaque is often noncontrast (VNC) image can be made and the con-
compromised by the concomitant presence of calcifica- tribution from iodine enhancement overlaid on it.
tions. Dual-energy CT can effectively subtract out the The Siemens dual-energy application suite provides a
56 Section I  Advanced Modalities: Protocols and Optimization

fusion multiplanar reconstruction (multiplanar refor- conventional MDCT scanner in which the individual
mat) tool for postprocessing and visualization. The rows of detectors have been replaced by a 2-D digital
VNC image can be fused with the iodine image in flat-panel detector. The detector has an active area of
any proportion. For example, at a setting of 50% VNC 40 cm × 30 cm. Its digital flat-panel detector makes it
and 50% iodine overlay, a fused image is displayed in ­capable of ultra-high spatial resolution, and the volu-
which each pixel is equally weighted by the VNC and metric coverage of the detector allows studies of whole-
iodine contributions. The visualization tool allows the organ perfusion, such as perfusion of the liver, kidney,
operator to separate window-level settings for each or brain. Furthermore, the gantry can rotate continu-
component. ously while projection data are being acquired, giving
fpVCT the added capability of dynamic CT scanning.
In an fpVCT scanner, Z-direction coverage up to 18
Wide-Coverage MDCT Scanners
cm around the isocenter by source-side collimation in
A limitation of current MDCT scanners is their small the Z-direction is possible. This is large enough to scan
Z-axis coverage. Clinical scanners with 64 detector an entire human head in one rotation. The rotation time
rows provide approximately 4 cm of coverage along the of the gantry can be varied from 2 to 20 seconds. Native
Z-dimension. A simple way to increase Z-coverage is to spatial resolution of the flat panel is a 150-μm cube.
use a greater number of detector rows. Toshiba America The wide area detector used by the fpVCT proto-
Medical Systems Inc. (Tustin, CA, USA) recently intro- type enables the operator to scan from a fixed angular
duced the Aquilion 320, which has more than five position with a high image frame rate as well as scan
times the detector coverage of a 64-slice CT scanner. The ­continuously while the gantry is rotating. This flexibility
advantage of such wide coverage is obvious. In 1 sec- gives rise to the following scanning modes.
ond or less a volume as large as 16 cm can be scanned. Ultra-high resolution mode: The fpVCT system can be oper-
This is wide enough to capture most organs, including ated in the standard CT scanning mode by acquiring
the brain, with one single rotation of the gantry. Phillips projections during a full rotation and reconstructing
Medical Systems (Best, The Netherlands) has announced them as a volumetric stack. The only difference is that
a system with 128 detector rows. the entire volume is acquired in one rotation, and
Wide-volume coverage supported with continuous images have a much higher resolution because of the
gantry rotation can produce time-resolved volumetric inherent spatial resolution of the flat-panel detector.
images of the organ being studied. This is referred to For ultra-high spatial resolution scanning the detector
as dynamic volumetric CT. Dynamic CT permits visualiza- is read out in the 1 ´ 1 binning mode. In this mode
tion of time-evolving processes, such as ­neuroperfusion, every pixel is read out separately, and a spatial resolu-
tumor permeability, AVM blood flow patterns, and tion of approximately 150 μm is achieved. In order
aneurysm pulsations. to improve the signal-to-noise ratio and increase the
An increased number of detector rows proportion- frame readout rate, a 2 ´ 2 binning mode is used. In
ately increases the volumetric coverage if there is a con- this mode, four neighboring pixels are averaged to
comitant increase in the number of readout channels make one effective pixel with outstanding spatial res-
and the bandwidth of the slip ring to transfer data from olution of approximately 200 μm. Despite this quan-
the rotating gantry to the stationary hardware. Larger tum improvement in spatial resolution compared
Z-coverage also leads to a much wider cone angle, with with MDCT, the low contrast resolution is quite rea-
attendant deterioration of the slice selectivity profile fur- sonable and approaches 5 HU in slices 10 mm thick.
ther from the isocenter. Dynamic CT mode: fpVCT has the ability to monitor a
In typical scanning, the patient is translated through volume of interest continuously over a period of time.
the gantry bore in one direction during the scan. Effec- The current prototype can rotate continuously for 80
tive Z-coverage can be increased by using back-and-forth seconds while acquiring projection data. The rotation
motion of the patient table. Newer 4-D scanning modes time can be varied from 2 to 20 seconds. This enables
have recently been introduced by different vendors (e.g., observation of time-evolving processes such as first-
Adaptive 4D Spiral, Siemens Medical Solutions, Forch- pass dynamics of a contrast bolus, aneurysmal pulsa-
heim, Germany; Shuttle Mode CT, GE Healthcare Inc., tions, blood flow pattern through an AVM, and tumor
Princeton, NJ, USA). These modes allow larger Z-axis vascularity. This feature is further enhanced by the
coverage up to 27 cm using only 64 detector rows that fact that fpVCT can cover a large volume in each rota-
span only 4 cm. Thus, it is feasible to acquire dynamic tion. If the temporal resolution is short enough and
scans of a complete organ even on a 64-slice scanner. the imaging is conducted for an appropriate length of
This technology generates robust, artifact-free neuro- time, depending on the tissue type being studied, the
perfusion and cardiac imaging at temporal resolution evolution of a contrast bolus can be followed through
less than 200 ms. It also may be used for 3-D CT-guided the arteries, soft tissue, veins, viscera, and even bone
interventions. marrow. Using such a dataset, a perfusion study of
these tissues can be performed, making it possible to
combine fpVCT angiography and fpVCT perfusion in
Flat-Panel Volume CT
one dynamic imaging process.
The fpVCT is a uniquely designed prototype scanner The temporal resolution of such a dataset will be equal
with enhanced capabilities over conventional MDCT. to the rotation time of the gantry. In general, a higher
An fpVCT scanner can be considered a variant of the rotation speed improves the temporal resolution at
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 57

the expense of image noise and spatial resolution and are too sick to travel to a fixed CT ­scanner. These

SECTION I
because of the fixed frame rate of the detector. By scanners also enable deployment of advanced imaging
increasing the rotation speed, the number of frames in nontraditional areas, such as outpatient clinics, bat-
used in reconstruction is proportionately decreased. tlefront and military locations, ships, and sports facili-
Fluoroscopy mode: The imaging chain of the fpVCT can ties. Mobile CT scanners have also proven to be a useful
be “parked” in one angular position and real-time tool in operating rooms.
projection data acquired. Such a fluoroscopy mode Mobile scanners generally provide a headrest system
enables visualization and intervention from any user- so that images can be obtained in a sterile environment
selectable angular position. intraoperatively. Intraoperative scans, which can be
Because of the various application modes that encom- obtained in minutes, provide vital data with minimal
pass radiography, fluoroscopy, and tomography in a sin- disruption or delay. For example, they can be used to
gle scanner, fpVCT can be thought of as an omni-scanner ascertain the completeness of tumor or AVM resection.
that may represent an important tool for neuroimaging The CereTom (NeuroLogica Corporation) was the
in the future. Although this prototype scanner is still in first portable CT scanner. It is an eight-slice scanner that
its research phase, the preliminary results look promis- can generate images with slice thickness varying from
ing. For example, by virtue of its high ­resolution, fpVCT 1.25 to 10 mm. In a 25-cm field of view configured for
is very helpful in visualizing small structures such as the dedicated head scanning, it offers a resolution compa-
ossicles and the pathologies involving the footplate of rable to that of clinical MDCT. The tradeoff between the
the stapes and other middle and inner ear structures. radiation dose delivered to patients and image quality
Other applications, such as dynamic imaging and real- is ­important for all CT scanners, including mobile CT
time fluoroscopy, currently are being developed and scanners. Because mobile scanners are designed for bed-
explored. It is expected that the fpVCT will play a vital side imaging of the head and neck, the dose to the per-
role in diagnosing small emboli, arterial dissections, and sonnel is another important consideration.
other neurovascular pathologies. Animal experiments Mobile scanners typically are designed for multiple
with dynamic mode have shown that the ultra-high spa- operating modes that trade off image quality for faster
tial resolution can clearly help in demarcating the narrow scan time and reduced dose. For example, in the low-
vessels of the brain (Figures 1-87 and 1-88). Aneurysm dose mode (2 seconds per rotation), the CereTom deliv-
morphology and surface features, such as blebs and per- ers a radiation dose that is below or comparable to that of
forators, can be well seen using this ­technology. Animal the American College of Radiology’s diagnostic reference
experiments have demonstrated dynamics of tumor value. The CereTom can be operated in “standard” or
vascularity that may be useful in planning treatment. “high-quality” modes that take 4 and 6 seconds per rota-
Together these features offer the promise of improved tion, respectively. With these modes come corresponding
tomographic imaging in the future, with radiation expo- increases in image quality, radiation dose, and scan time.
sure comparable to that of routine MDCT. According to the manufacturer’s specifications for the
CereTom scanner, at 120 kVp and 7 mAs, the CTDI100
values for rotation speeds of 2, 4, and 6 seconds are 44.8,
Portable CT Scanners
83.5, and 122 mGy, respectively. At 140 kVp and 7mAs,
Compact mobile CT scanners for head and neck imag- these values increase to 65.3, 126.8, and 176.3 mGy,
ing recently have become commercially available. Por- respectively, and are within expected dose levels for high-
table CT machines, such as the CereTom (NeuroLogica quality head CT scans. The choice of imaging mode to be
­Corporation, Danvers, MA, USA), provide a new option used is dictated by the patient’s clinical condition. For
for critically ill patients. Instead of transporting the example, for a postoperative scan assessing the position
patient to a fixed scanner in a radiology suite, the scanner of a ventriculostomy catheter, a fast 2-second scan would
is brought to the patient so that he or she can be scanned suffice. However, if the clinical question is to determine
in the ICU bed. Besides patient safety, mobile point-of- if an acute infarction has occurred, a high-quality scan
care imaging allows faster response to imaging requests. may be warranted to assess gray–white differentiation.
Our experience has shown that use of the Cere- The scanner provides protective lead curtains so that
Tom CT scanner is associated with a 58% reduction in the scatter radiation is well within ALARA (as low as rea-
request-to-scan times. It also improves personnel utili- sonably achievable) standards. The specifications for the
zation because critical care nurses need not leave their CereTom state that “at a distance of 2 meters (6 feet)
premises to bring the patient to the radiology suite. from the isocenter, an operator can perform over 26
Because of their ease of use, these scanners are ideal scans per day, for 250 days per year without any addi-
for confirming the position of a shunt catheter, fol- tional lead protection.” Therefore, the dose to the per-
low-up intracranial hemorrhage, midline shift, or any sonnel conducting the scan is well within the acceptable
other neurologic process that may evolve over time and range when proper precautions are taken.
requires tracking by repeat CT scanning. Besides routine Figure 1-89 illustrates the power of a mobile CT scan-
follow-up head CTs, the current scanners can perform ner in a neurology ICU setting. The patient, a 43-year-
contrast-enhanced CT, CTA, CT perfusion, and even old woman, was found unconscious in her house by
xenon perfusion without sacrificing image quality. ­Emergency Medical Services (EMS). The patient was
Mobile scanners are the tool of choice in the neurology in asystole, but EMS achieved a complex perfusing
ICU setting, where patients often have multiple arterial, rhythm in the field after administering epinephrine
venous, and electrical lines, are ventilator ­dependent, and atropine. In the neurology ICU, the patient, who
58 Section I  Advanced Modalities: Protocols and Optimization

Figure 1-87 Flat-panel volume computed tomographic images of Macaca sylvanus showing dynamic filling of the cervical arteries and veins.
Left, Very early during contrast injection, none of the vessels are visible. Second from left, Arterial phase of the bolus shows peak arterial opacifica-
tion. Third image from left, A bit later in time, both arteries and veins are visible. Right, Venous phase.

Figure 1-88 Ultra-high spatial resolution of flat-panel volume computed tomography enables visualization of very small vessels of the brain.
In this case, the anterior cerebral artery of a Macaca sylvanus, measuring approximately 400 μm at the genu, can be visualized.
 Chapter 1 Multidetector Computed Tomography as a Problem-Solving Tool in Neuroradiology 59

SECTION I
A B

C D
Figure 1-89 Multiple axial computed tomographic slices acquired using a portable scanner (CereTom, NeuroLogica Corporation, Denvers, MA,
USA) in a patient with a history of prolonged asystole. Even with a portable device, diffuse loss of gray–white differentiation and sulcal effacement
can be appreciated and is compatible with cerebral edema, as is the effacement of perimesencephalic cisterns and uncal herniation. Multiple foci
of infarctions suggest widespread hypoxic ischemic injury, which is most severe in the areas of high metabolic activity, such as the basal ganglia.

was ­hyperkalemic with a blood potassium level in the low-contrast detectability to demonstrate subtle differ-
range from 6.1 to 7.2, was deemed too unstable to ences in attenuation required for neuroimaging.
undergo a regular head CT or MRI. A portable CT scan
using the CereTom was performed. Figure 1-89 shows
diffuse loss of gray–white differentiation and sulcal Suggested Readings
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 chapter 2

Magnetic Resonance Imaging

as a Problem-Solving Tool
Jane J. Kim and Pratik Mukherjee

INTRODUCTION MR IMAGE GENERATION

Computed tomography (CT) and magnetic resonance To form images, magnetic field gradients are applied
imaging (MRI) have been the mainstays of diagnostic that steadily increase in strength along a particular direc-
neuroradiology into the first decade of the twenty-first tion. Because of the gradients, a proton in one location
century. CT has shown particular utility in the evalua- will be at a different magnetic field strength and there-
tion of bone, blood, calcium, and metal in the brain and fore will precess at a different Larmor frequency than a
spine. Contrast-enhanced CT angiography also affords proton in another location along the gradient direction.
exquisite detail of the cerebrovascular system. However, To localize protons within the body in all three orthogo-
MRI has become the dominant technique for problem nal axes (x, y, and z), three mutually perpendicular gra-
solving in neuroradiology due to its inherent multipla- dients are applied, designated the frequency-encoding,
nar and three-dimensional (3D) capability, sensitivity, phase-encoding, and slice-select gradients.
and versatility and its multitude of available contrast Two-dimensional MRI uses a specific RF pulse to
mechanisms for evaluating the diverse tissues of the excite a slice of tissue. The slice-select gradient is turned
neuraxis. Using appropriate procedures and widely on while the excitatory RF pulse is given so that the
accepted precautions, MRI is very safe, with no exposure only nuclei to respond are those in the slice whose Lar-
to ionizing radiation or iodinated contrast media. mor frequency matches that of the exciting RF pulse.
The stronger the slice-select gradient, the thinner the
PHYSICAL BASIS OF MRI excited slice. The frequency-encoding gradient is used
during detection or “readout” of the MR signal. The
The MR signal from biologic tissues arises when an phase-encoding step, which is performed between slice
external magnetic field (B0) is applied and the hydro- selection and frequency-encoded readout, must be per-
gen nuclei, primarily from water protons, begin to formed many times at different gradient strengths, mak-
rotate (“precess”) at the resonance frequency, known ing this one of the key determinants of the length of
as the Larmor frequency, and align along the direction a scan. Two-dimensional imaging typically produces a
of the B0 field, designated the z-axis or the longitudi- series of slices that are greater than 1 mm each in thick-
nal direction. The precession of the aligned hydrogen ness and may be contiguous and consecutive, contigu-
nuclei at the Larmor frequency creates a net magne- ous and interleaved, or noncontiguous with small gaps
tization, but this cannot be detected along the z-axis; between the 2D slices.
it can only be detected when its magnetization lies in In 3D imaging, the RF pulse and slice-select gradi-
the transverse (x/y) plane orthogonal to the z-axis. To ent excite an entire volume of tissue along the z-axis,
measure the MR signal, a radiofrequency (RF) pulse is rather than a single thin slice. Phase encoding is per-
applied to tip the net magnetization by a certain angle formed in the two directions mutually orthogonal to the
(the flip angle) toward the transverse plane. Immedi- ­frequency-encode direction, not just in one direction as
ately after the RF pulse, protons in the transverse plane in 2D imaging, and is followed by the frequency-encoded
precess together at the same frequency and coherently readout. Three-dimensional imaging can generate very
at the same phase, creating a signal. However, the sig- thin slices (each <1 mm) that are contiguous with each
nal is rapidly lost as inhomogeneities in the magnetic other, permitting excellent multiplanar reconstructions.
field cause the nuclei to lose their phase coherence However, 3D imaging is slower than 2D imaging because
(“dephase”) and spin at different frequencies, a pro- it performs the relatively time-consuming process of
cess known as free induction decay (FID). FID cannot phase encoding in two directions, not just one.
be measured directly for imaging purposes. Instead, an Generation of an actual image from an MR signal
echo of the FID, either a spin echo or gradient echo, usually requires multiple excitations with an RF pulse to
must be produced by rephasing the nuclei. These two produce enough data for the image. The period between
basic rephasing methods are the basis for many RF excitations is the time to repetition (TR); the period from
pulse sequence designs that result in the diverse forms RF excitation to echo readout is the time to echo (TE). The
of contrast available from MRI. measured echoes from a particular slice are sampled and

61
62 Section I  Advanced Modalities: Protocols and Optimization

A B
Figure 2-1 Importance of proper coil selection. Patients with prion disorders, such as Creutzfeldt-Jakob disease (CJD), may have high signal in
the cerebral cortex, as was the case for a patient (A) who had bright cortical signal particularly in the left cerebral hemisphere (arrows). A different
patient (B), who did not have CJD, was imaged in a surface coil and showed high signal in the paramedian frontal cortex bilaterally (arrows). This
is an artifact from the closer proximity of superficial tissues to the surface coil. Because of the potential for confusion with artifactually inhomoge-
neous signal, diagnosis of CJD may be easier with a volume coil, which encircles the entire head and provides better signal uniformity.

then encoded within k-space. The k-space is a mathemat- transmit the RF pulse. Surface coils have very high signal-
ical construct consisting of a blank grid or matrix onto to-noise ratio, especially for superficial structures close
which frequency and phase data can be mapped prior to to the coil. However, they have a reduced field of view
their transformation into an MR image. In k-space, fre- (FOV) and are more prone to inhomogeneity of signal
quency information typically is mapped along the x-axis across an MR image, with signal loss for deeper tissues.
and phase information along the y-axis. In a conven- Phased-array coils are composite coils composed of mul-
tional spin-echo sequence, one echo generates the data tiple small surface coils arranged to form an array. These
for a single line in k-space and corresponds to a single have been developed to try to increase the FOV while
phase-encoding step. The center of k-space contains maintaining the high signal-to-noise ratio of surface
information about general form (low spatial resolution) coils. Imaging for Creutzfeldt-Jakob disease illustrates
at high image contrast. The periphery of k-space holds the importance of proper coil selection (Figure 2-1).
information about fine detail (high spatial resolution) at
low image contrast. The data within k-space are rendered TISSUE CONTRAST IN MRI
into an image by Fourier transformation, a computerized
mathematical process of MR signal decoding that con- T1, T2, and proton density are the fundamental param-
verts frequency information into the pixels of an image. eters of MRI and determine the contrast between tis-
sues. Following the excitatory RF pulse and tilting of the
net magnetization into the transverse or x/y-plane, the
RF COILS
transverse magnetization is lost at a rate determined by
RF antennas called coils are used to transmit the RF pulse a particular tissue’s T2 relaxation time. Simultaneously,
and receive the MR signal. Separate coils can be used for longitudinal magnetization along the z-axis is regained
transmission and reception, or the same coil can be used at a rate set by the tissue’s T1 relaxation time.
for both functions. MR coils may be constructed to have Fat has a shorter T1 than cerebrospinal fluid (CSF)
different regions of coverage. A volume coil is a circumfer- and recovers its longitudinal magnetization quickly fol-
ential structure that surrounds the body part completely, lowing an RF pulse. If TR is short, fat recovers more of
whereas a surface coil is typically flat or curved and placed its longitudinal magnetization than CSF and produces
on the skin surface overlying a specific region of interest. a stronger MR signal. More longitudinal magnetization
Volume coils both transmit and receive the MR signal. leads to more transverse magnetization and stronger sig-
They encircle the body part completely, so they provide nal with the next RF pulse. Making TR short emphasizes
very uniform signal throughout the entire MR image. the differences in T1 relaxation times of tissues, so tissues
A typical volume coil used for neuroimaging is the bird- with short T1, such as fat, melanin, and protein, pro-
cage head coil. Surface coils are generally receive-only duce high signal. MR sequences that emphasize tissue
coils, so a separate volume head or body coil is needed to differences in T1 relaxation are designated T1 weighted.
 Chapter 2 Magnetic Resonance Imaging as a Problem-Solving Tool 63

Fat has a shorter T2 relaxation time than CSF and of (1) macroscopic magnetic field inhomogeneities due

SECTION I
loses its transverse magnetization (T2 signal) more rap- to factors such as adjacent ferromagnetic objects, non-
idly. Making TE long provides greater time for transverse uniformities in the B0 magnetic field, and tissue inter-
magnetization to decay and emphasizes differences in faces, and (2) microscopic magnetic interactions among
T2 relaxation times of tissues. When TE is long, tissues spinning nuclei. The loss of magnetization due to both
with short T2 relaxation times (fat) show greater loss of microscopic and macroscopic factors is termed T2*
T2 signal and appear dark, whereas tissues with long T2 relaxation. Signal loss due only to microscopic nuclear
relaxation times (CSF) retain a larger portion of their T2 interactions is “true” T2 decay and occurs more slowly
signal and appear bright. MR sequences that use long TE than T2* decay.
to emphasize tissue differences in T2 relaxation times The 180-degree refocusing pulse is able to rephase
are designated T2 weighted. nuclei that have begun precessing at different frequen-
If TR is long and TE is short, neither the T1 nor T2 dif- cies and can prevent the signal loss that is due to mac-
ference between fat and CSF is emphasized. Any differ- roscopic factors. However, it cannot prevent the signal
ence in contrast observed between the two tissues is then loss that is due to random, microscopic nuclear interac-
due to differences in the proton densities of the tissues. tions (i.e., T2 decay). The spin echo that results from the
Tissues with higher proton density supply greater signal rephasing effects of the 180-degree pulse is still suscep-
than tissues with lower proton density. MR sequences tible to T2 decay; therefore, SE sequences with long TE
that use long TR and short TE to capture differences in are said to be T2 weighted (not T2* weighted).
tissue proton density are designated proton-density (PD) Figure 2-2, A illustrates the pulse sequence diagram
weighted sequences. for the spin-echo technique.

Image Quality Gradient Refocused Echo

In MR, image quality depends on spatial resolution If the 180-degree refocusing pulse is not given, an echo
and the signal-to-noise ratio. Like CT, spatial resolu- of the FID can still be produced by using gradients of
tion reflects voxel size. Pixel size influences in-plane or opposite polarity (equal strength, opposite direction)
x/y-axis spatial resolution, whereas slice thickness deter- to first dephase and then rephase the spins. Opposite-
mines z-axis spatial resolution. Therefore, spatial reso- polarity lobes of the frequency-encoding gradient are
lution can be improved by reducing voxel size through used to bring spins together in phase and produce
decreasing FOV, increasing matrix size, or obtaining a gradient echo at time TE. Because they do not use a
thinner slices. However, reducing voxel size to improve 180-degree refocusing pulse, gradient-recalled echo
spatial resolution tends to increase the relative noise in (GRE) images are prone to signal loss from both mac-
an image. Spatial resolution and signal-to-noise ratio roscopic and microscopic factors (T2* decay). Depend-
are competing considerations. ing on various sequence parameters, GRE sequences can
The sampling bandwidth refers to the rate at which be T1 or T2* weighted, but typically not T2 weighted
an echo is sampled. A high bandwidth samples an echo (exceptions are discussed later). Figure 2-2, B illustrates
quickly but requires a stronger frequency-encoding gra- the components of a GRE sequence.
dient and results in a greater range of frequencies. A low Unlike SE, GRE sequences use small flip angles less
bandwidth takes longer to sample an echo but has a than 90 degrees. Flip angles less than 90 degrees do not
smaller range of frequencies and includes less sampling completely eliminate longitudinal magnetization. Some
of noise. High bandwidths reduce acquisition time, so longitudinal magnetization remains, so it recovers more
there is less opportunity for image degradation from completely before the next pulse. This permits use of a
signal decay. Low bandwidths prolong acquisition time shorter TR and helps achieve faster scan time. In GRE
but improve the signal-to-noise ratio. sequences, the tissue weighting depends on TR, TE, and
the value of the flip angle. Larger flip angles accentu-
ate differences in T1 relaxation time because more lon-
Basic MR Sequences
gitudinal magnetization must recover to produce the
Spin echo and gradient echo are the only two basic image. Therefore, larger flip angles produce T1-weighted
sequences in MRI; all other sequences are variations images.
of one of these two sequences. To create either a spin “Spoiling” or “refocusing” transverse magnetization
echo or gradient echo following the FID, a specific pulse provides another means of tissue weighting. To reduce
sequence must be designed. A pulse sequence diagram scan times, GRE sequences frequently use very short TR
illustrates the series and timing of requisite events, (shorter than the T2 relaxation times of many tissues)
including application of the RF pulse and various gradi- so that transverse magnetization does not have time
ents, to produce the sampled echo. to decay completely before the next excitatory pulse.
In this situation, there is both residual transverse mag-
netization and recovered longitudinal magnetization
Spin Echo
just before the next RF pulse. If the residual transverse
The spin echo (SE) sequence is created by following the magnetization is “spoiled” or destroyed, only the lon-
90-degree excitatory pulse with a 180-degree refocusing gitudinal magnetization is left for the next RF pulse,
pulse at time TE/2. Following the 90-degree RF pulse, resulting in T1-weighted images. Spoiling of transverse
transverse magnetization (FID) is quickly lost because magnetization is achieved by use of spoiler gradients or
64 Section I  Advanced Modalities: Protocols and Optimization

A B

C
Figure 2-2 Pulse sequence diagrams. A: Spin echo. Following the 90° excitation pulse, which occurs at the same time as the slice-selection gra-
dient, free induction decay quickly disappears. The 180-degree refocusing pulse given at time TE/2 rephases the spins to create the spin echo that
is read out at time TE with application of the frequency-encoding gradient. The phase-encoding step must be performed many times at different
gradient strengths, so it is pictured with multiple lines denoting different gradient amplitudes. B: Gradient echo. Following the radiofrequency
pulse (with flip angle α <90 degrees), free induction decay is rapidly lost. No 180-degree refocusing pulse is given; instead, opposing lobes of
the frequency-encoding gradient are used to first dephase then rephase the spins, creating an echo at time TE. The negative (dephasing) lobe of
the frequency-encoding gradient is shown below baseline, and the positive (rephasing) lobe is shown above baseline. C: Inversion recovery and
fluid-attenuated inversion recovery (FLAIR). A 180-degree pulse is given at the beginning of the sequence, which flips the net magnetization vector
into the −z-axis. Tissues recover longitudinal magnetization according to their T1 properties, and cerebrospinal fluid (CSF), with long T1, regains
magnetization more slowly than other tissues. The 90-degree excitatory pulse at time TI is given at the null point for CSF, when there is no longi-
tudinal magnetization for CSF. However, other tissues have recovered longitudinal magnetization, which is flipped into the transverse plane with
the excitatory pulse to generate the magnetic resonance signal. FLAIR is performed on a spin-echo sequence.

RF ­spoiling, a discussion of which is beyond the scope the amount of transverse magnetization that remains.
of this chapter. These T1-weighted GRE sequences are Because recovery of longitudinal magnetization is
known as spoiled or incoherent GRE sequences. determined by T1 and decay of transverse magnetiza-
Alternatively, unspoiled or coherent GRE imaging tion by T2, these sequences reflect a mixture of T1 and
preserves the transverse magnetization that accumu- T2 weighting. Note that if TR is sufficiently long to
lates between RF pulses in short TR sequences. The allow complete decay of transverse magnetization and
subsequent RF pulse rotates residual transverse mag- leave only longitudinal magnetization, the unspoiled/
netization into the longitudinal plane while flipping coherent sequence becomes T1 weighted, much like a
recovered longitudinal magnetization into the trans- spoiled/incoherent GRE.
verse plane. Over time and with successive RF pulses, Another consequence of preserving residual trans-
there is an intricate mixing of transverse and longitu- verse magnetization in unspoiled GRE imaging is the
dinal components known as steady-state free preces- generation of a spin echo with the next excitatory RF
sion. Unlike spoiled GRE sequences, signal intensity in pulse. The excitatory pulse behaves like a refocusing
unspoiled sequences depends not only on the amount pulse on residual transverse magnetization and is con-
of longitudinal magnetization that has recovered but on ceptually similar to (though less effective than) the
 Chapter 2 Magnetic Resonance Imaging as a Problem-Solving Tool 65

180-degree refocusing pulse used in SE imaging. The T2-weighted images because T2-weighted sequences

SECTION I
residual ­transverse magnetization that was becom- use long TR and long TE. Rapid acquisition with refocused
ing dephased is suddenly refocused and generates a echo (RARE) sequences were developed to reduce imag-
spin echo in addition to the usual FID that is created ing time. Commercially, these are known as fast spin-
immediately after an RF pulse. Depending on sequence echo (FSE) or turbo spin-echo (TSE) sequences. In this
design, either the FID or spin echo can be favored to approach, each 90-degree RF pulse is followed by multi-
achieve more T2* or T2 weighting, respectively. Balanced ple 180-degree refocusing pulses (not just one) in order
GRE sequences are constructed so that all gradients are to generate more spin echoes and fill multiple lines of
balanced and the FID and spin echo signals coincide, k-space per excitation pulse. The number of echoes gen-
achieving a complex mix of T1 and T2 weighting. erated after each excitatory pulse is termed the echo train
length (ETL) and corresponds to the number of phase-
encoding steps acquired in a single TR. Therefore, FSE or
Inversion Recovery Imaging
TSE reduces the scan time to 1/ETL of the time required
Inversion recovery imaging applies a preparatory pulse for standard SE imaging.
just before an SE or GRE sequence to emphasize T1 The k-space demonstrates a certain symmetry and
­contrast or to eliminate signal from undesired tissues redundancy of information that allows an image to
such as CSF or fat. A 180-degree inversion pulse is first be derived from a portion of the complete dataset. If
given to flip the initial net magnetization vector from enough echoes are collected to fill one-half of k-space
the +z axis to the –z axis. Nuclei recover longitudinal after a single 90-degree excitatory pulse (designated a
magnetization from –z to +z according to their T1 prop- shot), the data in the other half of k-space can be inferred
erties. If an excitatory 90-degree pulse is given during based on the known symmetry of k-space. The tech-
relaxation (at inversion time TI), nuclei with shorter T1 nique used to produce images from a half set of data
will have recovered more longitudinal magnetization is known as single-shot RARE (or commercially as half-
and thus produce greater transverse magnetization and Fourier acquisition single-shot turbo spin echo [HASTE]
MR signal. This creates T1 weighting. or single-shot fast spin echo [SSFSE]).
As nuclei recover longitudinal magnetization from A similar rapid imaging technique using gradient
–z to +z following the 180-degree inversion pulse, they echoes is designated echo planar imaging (EPI). In EPI,
pass through a null point at which the net magnetiza- the single excitatory pulse or shot is followed by a long
tion vector is zero. A 90-degree excitatory pulse given stream of gradient echoes generated by rapidly switch-
at this time for CSF (or fat) would have very little ing gradients. The multiple gradient echoes fill all of
effect on and generate no MR signal from CSF (or fat). k-space after a single shot. EPI is one of the fastest MR
In this manner, specific tissues can be made dark on sequences available, so it is used for diffusion-weighted
imaging. Short tau inversion recovery (STIR) is the name imaging (DWI). Because DWI characterizes the micro-
of the sequence used for fat elimination. Because fat scopic movement or diffusion of water molecules
has a relatively short T1, STIR sequences typically through tissue, corruption by bulk macroscopic motion
use inversion times of approximately 150 to 175 ms due to long scan time cannot be permitted.
at 1.5 T. Fluid-attenuated inversion recovery (FLAIR) is Figure 2-3 summarizes the differences between single
the name of the sequence used for CSF suppression. and multiple echo techniques. Note that all multiple
Because water has a long T1, FLAIR sequences typically echo techniques are subject to image contrast blurring
use inversion times ranging from 1,800 to 2,400 ms at because transverse magnetization decays over the course
1.5 T. Figure 2-2, C illustrates a typical inversion recov- of the long echo train. This T1, T2, or T2* blurring
ery sequence. increases with ETL and reaches its extreme in the single-
The concept of tissue contrast is more complex than shot techniques (HASTE, SSFSE, and EPI).
simple T1 or T2 weighting for FLAIR. Whereas FLAIR
sequences have long TE and are T2 weighted so that NORMAL APPEARANCE
fluid other than CSF is bright, an element of T1 weight-
OF IMAGES WITH MRI
ing is also present. The 180-degree inversion pulse intro-
duces T1 weighting, because the degree to which tissues On T1-weighted images of the normal adult brain,
recover longitudinal magnetization before the excita- white matter is of slightly higher signal intensity than
tion pulse is given depends on their T1 properties. gray matter. However, the unmyelinated or partially
myelinated white matter of infants younger than 2 years
is hypointense to gray matter. Fat is bright and CSF is
Fast Imaging Techniques
dark on T1-weighted images, as previously discussed.
The main drawback of conventional SE imaging is its On T2-weighted images of the normal adult brain,
long imaging time. Long imaging time results because white matter is hypointense to gray matter. The unmy-
each excitatory RF pulse generates a single echo that elinated or partially myelinated white matter of infants
fills only a single line of k-space, corresponding to a younger than 2 years is hyperintense to gray matter
single phase-encoding step. The SE technique does not on T2-weighted images. Fat is dark and CSF is bright
considerably lengthen the time required for obtaining on spin-echo T2-weighted images. However, fat may
T1-weighted images because T1-weighted sequences appear bright on FSE or TSE T2-weighted images due to
use short TR and short TE. However, the SE technique a decrease in a phenomenon known as J-coupling. Any
significantly lengthens the time required for obtaining pathologic process that increases tissue water ­content
66 Section I  Advanced Modalities: Protocols and Optimization

D
Figure 2-3 Comparison of single and multiple echo techniques, following a single excitatory pulse. A: An axial level in the brain is determined
by the slice-selection gradient at the time of radiofrequency excitation. B: In conventional spin echo, a single 180-degree refocusing pulse after
the excitatory pulse produces a spin echo that fills a single line of k-space (shaded in gray). The sequence must be repeated, with phase encoding
performed at a different amplitude, to generate another spin echo that fills a different line of k-space. C: In fast or turbo spin echo, each excitatory
pulse is followed by n number of 180-degree refocusing pulses (five in our case) that generate n echoes to fill n lines of k-space. The echo train
length (ETL) is 5 and scan time is 1/5 (1/ETL) of the conventional spin-echo sequence. Phase encoding is performed at a different amplitude for
each echo, to fill a different line of k-space. D: In single-shot echo planar imaging, the excitatory pulse is followed by rapid gradient switching that
generates a long stream of gradient echoes enough to fill all of k-space after a single pulse.

will be readily seen as bright signal on T2-weighted c­ haracteristically at the brain–skull interface and in the
sequences. spine on sagittal images, where it can simulate a syrinx.
Truncation artifact can be reduced by decreasing inter-
Artifacts Associated with MRI, face contrast (e.g., by using fat suppression) or by increas-
Including False Positive/False ing matrix size. Motion/ghost artifacts typically occur in
the phase-encoding direction because time-consuming
Negative
phase-encoding steps allow more time for motion to
Some of the common MR artifacts are discussed here. disrupt the MR signal and create artifact. Both patient
Artifacts associated with specific MR sequences are and physiologic motion (e.g., CSF or blood pulsation)
explained later in the chapter. can cause artifact, which may appear as blurred areas
Wraparound/aliasing occurs when the body part or as “ghosts” (discrete lines or objects). Motion arti-
imaged is larger than the FOV, causing “wraparound” fact can be reduced by using fast imaging techniques or
of the data outside the FOV. This occurs along the applying presaturation pulses to minimize signal from
phase-encoding direction(s) and can be eliminated moving or pulsating structures. If the artifact obscures a
by enlarging the FOV or by increasing the number of structure of interest, swapping the phase-encoding and
phase-encoding steps. Truncation or Gibbs ringing arti- frequency-encoding directions can redirect the artifact
fact occurs because of undersampling or truncation away from that specific structure.
of high-frequency data. It appears as alternating light Chemical shift artifact occurs in the frequency-­
and dark bands at high–low signal tissue interfaces, encoding direction. Frequency encoding spatially
 Chapter 2 Magnetic Resonance Imaging as a Problem-Solving Tool 67

localizes the MR signal on the basis of frequency, and than CT. The following section highlights specific uses of

SECTION I
differences in frequency are automatically equated to dif- common MR techniques for clinical neuroimaging.
ferences in signal origin. The magnetic field experienced
by a proton is influenced by the precise chemical envi- SYSTEMS FOR ANALYZING IMAGES
ronment in which it resides. Electron clouds of adjacent USING MRI
chemical groups may partially “shield” a proton from
the applied gradient field so that the proton experiences Illustrated Approach
a slightly different magnetic field than its neighbor and
responds by precessing at a slightly different frequency 1. Spin Echo and Fast/Turbo Spin Echo
from its neighbor. The difference in precessional fre- SE has traditionally been considered the mainstay of
quency caused by the different chemical environment is neuroimaging. T2-weighted SE or FSE/TSE highlights
designated chemical shift. Within the same voxel, the pro- pathologic processes because of its sensitivity to fluid
tons in fat and water precess at slightly different Larmor and changes in tissue cellularity and often is superior to
frequencies (chemical shift) because they experience CT in depicting pathologic lesions (Figure 2-5). Appear-
different magnetic fields due to differential shielding by ance on T1 imaging can be helpful for identifying sub-
their electron clouds. Bright and dark signal at the fat– stances such as fat, melanin, and proteinaceous material
water interface results from mismapping of fat and water because they all appear bright on T1. Hemorrhage has
protons in the same voxel during frequency encoding variable appearance on T1-weighted and T2-weighted
and is known as chemical shift artifact. Chemical shift images depending on the age of the hematoma.
artifact can be reduced by suppressing signal from fat, Gadolinium-based contrast material can be adminis-
by switching frequency-encoding and phase-encoding tered intravenously to highlight pathology. Gadolinium is
directions to minimize disruption to a specific area, or a paramagnetic metal that, by itself, is toxic to the human
by increasing the sampling bandwidth. Increasing the body, so it must be tightly chelated to another substance
bandwidth increases the range of sampled frequencies such as diethylenetriamine-pentaacetic acid (DTPA)
and decreases the relative importance or conspicuity of before it is used. Gadolinium shortens T1 relaxation
the chemical shift difference. However, increasing the times, causing increased signal on T1-weighted images
bandwidth will reduce the signal-to-noise ratio. wherever the blood–brain barrier has been breached and
Susceptibility is a property of different materials that contrast material is able to enter (e.g., in tumor).
describes their interaction with a magnetic field. Cer-
tain materials, such as iron-containing hemorrhage or 2. Gradient Echo
­gadolinium-based contrast, weakly increase the local The lack of a 180-degree refocusing pulse and the spe-
magnetic field and are known as paramagnetic. Super- cific vulnerability to T2* decay can be exploited to detect
paramagnetic or ferromagnetic materials such as iron intracranial hemorrhage. Paramagnetic blood products
and various metal alloys more strongly increase and dis- create local magnetic field inhomogeneities, cause adja-
tort the local magnetic field, causing signal dropout and a cent spinning nuclei to dephase, and induce a striking,
warped appearance of nearby tissues. GRE sequences are characteristic signal loss on GRE sequences (Figure 2-6).
more prone to susceptibility artifact because they do not In contrast, blood can be more difficult to detect on SE
use a 180-degree refocusing pulse and signal dephases sequences, which are less sensitive to susceptibility effects
rapidly due to field inhomogeneities. Susceptibility arti- due to the 180-degree refocusing pulse. FSE and TSE
fact can be decreased by using SE rather than GRE tech- sequences are even less sensitive to hemorrhage than SE
nique (especially FSE or TSE with long ETLs), by using because they use multiple refocusing pulses. GRE MRI,
short TE (decreasing the time for dephasing to occur), especially at high magnetic field strength such as 3 T,
and by increasing the sampling bandwidth (faster acqui- is even superior to CT for detecting microhemorrhages
sition, decreasing the time for dephasing to occur). Alter- (e.g., due to traumatic brain injury) (Figure 2-7). This is
natively, susceptibility artifact may be used to advantage because susceptibility effects increase dramatically with
to identify very small and otherwise easily overlooked field strength, rendering high-field T2*-weighted GRE very
foci of hemorrhage, such as those found with trauma, sensitive to small amounts of blood breakdown products.
amyloid angiopathy, and cavernous malformations. The faster imaging time of GRE is particularly use-
These effects form the basis of susceptibility imaging and ful in scanning uncooperative patients or in 3D
are especially prominent at higher field strengths. imaging, which requires longer scan times than 2D
Figure 2-4 illustrates several commonly encountered imaging. In particular, 3D spoiled GRE sequences are T1
artifacts. weighted and provide excellent anatomic detail. Three-­
dimensional GRE T1-weighted sequences are useful
SPECIFIC USES FOR THE for evaluating subtle cortical abnormalities in seizure
patients or for characterizing tumor extension in con-
TECHNIQUE
junction with gadolinium-based contrast.
MR is the workhorse of neuroimaging for the adult brain.
It can be used to evaluate intracranial tumors, infection or 3. Fluid-Attenuated Inversion Recovery
inflammation, demyelinating processes, degenerative dis- FLAIR is typically a T2-weighted FSE/TSE sequence that
ease, ischemic injury, and developmental anomalies. Very uses an inversion pulse to eliminate the signal from
small anatomic structures, such as the sella turcica and CSF. It is useful for highlighting lesions that lie close
cranial nerves, can be depicted more precisely with MR to ventricles or sulci and are not as conspicuous on
68 Section I  Advanced Modalities: Protocols and Optimization

A B C

D E
Figure 2-4 Magnetic resonance artifacts. A: Wraparound or aliasing caused by small field of view. B: Typical location of pulsation artifact from
the dural venous sinuses in the phase-encoding direction (left/right). C: Lipoma in the left sylvian fissure causes chemical shift artifact in the
frequency-encoding direction (anterior/posterior). D: Susceptibility from patient’s dental braces causes marked signal loss and distortion on this
conventional spin-echo sequence. E: Fast/turbo spin-echo sequence in the same patient as in D shows dramatic reduction of artifact. The multiple
180-degree refocusing pulses used for fast/turbo spin echo make it less vulnerable to magnetic field inhomogeneities than conventional spin echo.
 Chapter 2 Magnetic Resonance Imaging as a Problem-Solving Tool 69

SECTION I
A B
Figure 2-5 T2-weighted magnetic resonance imaging is superior to computed tomography (CT) for detection of primary demyelinating dis-
eases, such as multiple sclerosis. A: Axial slice from a normal head CT in a 30-year-old woman with multiple sclerosis. B: Axial slice at approxi-
mately the same level as the CT image from a two-dimensional T2-weighted fast spin-echo sequence shows hyperintense periventricular and
subcortical white matter lesions (arrows) in a characteristic distribution for multiple sclerosis. The ovoid shape and orientation orthogonal to the
margin of the lateral ventricle displayed by the largest lesion in the left hemisphere are also characteristic of demyelinating plaques.

A B
Figure 2-6 Detecting hemorrhage with gradient-recalled echo (GRE) sequences. A: Coronal refocused or coherent GRE (T2*-weighted) image
shows numerous foci of susceptibility in a patient with familial multiple cavernous malformations. B: These lesions are much more difficult to
appreciate on coronal fluid-attenuated inversion recovery, which is typically performed on a fast/turbo spin-echo sequence and is less sensitive to
hemorrhage because of multiple refocusing pulses.

T2-weighted sequences (e.g., plaques of multiple scle- the sulci, failure of suppression of sulcal signal on
rosis or small infarcts abutting the cortex). Suppression FLAIR sequences suggests leptomeningeal disease with
of CSF signal allows for distinction between epidermoid replacement of normal CSF by blood (subarachnoid
cysts (bright) and arachnoid cysts (dark). Because FLAIR hemorrhage), pus (meningitis), or tumor (leptomen-
sequences normally suppress the signal of CSF within ingeal carcinomatosis). Because supplemental oxygen,
70 Section I  Advanced Modalities: Protocols and Optimization

A B
Figure 2-7 Magnetic resonance imaging with gradient-recalled echo (GRE) sequences is superior to computed tomography (CT) for detection
of traumatic microhemorrhage due to axonal shearing injury. A: Axial slice from a normal head CT in a patient who presented with head trauma.
B: Axial slice at the same level as the CT image from a two-dimensional T2*-weighted GRE sequence acquired at 3 T shows a microhemorrhage in
the subcortical white matter of the left superior frontal gyrus (arrow), indicating traumatic axonal injury.

A B C
Figure 2-8 Uses and artifacts of fluid-attenuated inversion recovery (FLAIR). A: Axial FLAIR image in a patient with tuberculous meningitis
shows high T2 signal within the subarachnoid space, particularly in the right parietal lobe, consistent with pus. B: Similar high T2 signal within
the subarachnoid space is observed on axial FLAIR in a patient requiring general anesthesia for sedation, consistent with high-flow oxygen artifact.
This high FLAIR signal in the subarachnoid space will disappear within minutes after cessation of oxygen supplementation. C: High T2 signal
around the cerebral aqueduct is typical of FLAIR artifact caused by incomplete cerebrospinal suppression.

especially at high concentrations, can artifactually create cisterns and third/fourth ventricles. Unsuppressed CSF
bright signal within the cisterns and sulci by reducing can flow very rapidly into these narrow areas, after the
the T1 relaxation time of CSF, no diagnosis of cisternal 180-degree inversion pulse but before signal sampling,
abnormality on FLAIR images should be made before creating bright FLAIR signal. Three-dimensional FLAIR
determining whether the patient was receiving oxygen is not as susceptible to CSF flow artifact as 2D FLAIR
during the MR scan. because the inversion pulse is applied to the entire vol-
FLAIR imaging is also limited in evaluation of the ume imaged and not just a single slice. Figure 2-8 illus-
posterior fossa because of CSF flow artifacts in the basilar trates some important features of FLAIR.
 Chapter 2 Magnetic Resonance Imaging as a Problem-Solving Tool 71

SECTION I
A B

C D
Figure 2-9 Uses and pitfalls of fat saturation. A: Axial unenhanced T1-weighted image demonstrates a large lesion mostly in the region of the
left lateral ventricle, with high signal layering nondependently in the frontal horns of both lateral ventricles as well as within the sulci bilaterally.
The intrinsic T1 shortening is suspicious for fat-containing dermoid with rupture into the ventricular system and subarachnoid space. B: Loss of
signal within the lesion, ventricles, and sulci following fat saturation confirms this diagnosis. C: Axial T1-weighted postgadolinium image with fat
saturation demonstrates abnormal high signal within the right retrobulbar fat, concerning for enhancement. D: Inspection of more caudal images
shows extensive susceptibility from dental hardware. This creates magnetic field inhomogeneities, leading to failure of fat saturation in the right
orbit, which should not be mistaken for enhancement.

4. Fat Saturation protons precess at slightly different frequencies from their

Frequency-selective fat saturation (FS) is an alternative Larmor frequency, making the saturation pulse less effec-
technique to STIR for eliminating signal from fat. FS tive (Figure 2-9). Field inhomogeneities are especially pro-
exploits the chemical shift between protons in fat and nounced along the periphery of the patient (farther from
those in water to reduce or remove the signal from the the isocenter of the magnet) and at ­air–tissue and bone–
fat. In FS, a 90-degree saturation pulse specifically tuned tissue interfaces, including the skull base and sinuses.
to the Larmor frequency of fat is given to flip only the
magnetization of fat into the transverse plane. This signal 5. Diffusion-Weighted Imaging
is then eliminated by a spoiler gradient. FS is clinically DWI is a way to display the molecular motion or dif-
useful for diagnosing lipomas or dermoid cysts. Good FS fusion of water protons within tissue. To achieve dif-
requires that the main magnetic field be exactly uniform fusion weighting, paired diffusion gradients of equal
throughout. Field inconsistencies can make fat or water magnitude are added to a spin-echo (T2-weighted) echo
72 Section I  Advanced Modalities: Protocols and Optimization

A B

C D
Figure 2-10 The anisotropic nature of diffusion requires that diffusion be assessed in multiple directions (A–C), then the images combined to
yield an isotropic map (D). Signal loss is appreciated when diffusion occurs along the direction of the gradient. Diffusion gradients were applied
along the transverse (A–x), anterior/posterior (B–y), and craniocaudad (C–z) directions, as diffusion occurs along fibers of the splenium of the
corpus callosum (A–x), frontoparietal white matter (B–y), and corticospinal tract (C–z).

planar sequence. The first diffusion gradient is applied perpendicular to axon bundles. Because of anisotropy,
before the refocusing pulse, and the second gradient diffusion is measured in multiple different orientations
is applied after the refocusing pulse. If there is motion (e.g., x, y, and z gradient directions), and the results are
of water protons (diffusion is not restricted), the diffu- combined into one “isotropic” image (Figure 2-10).
sion gradients cause dynamic dephasing of the moving MR signal intensity on DWI depends in part on the
nuclei that cannot be rephased, resulting in loss of MR strength of the diffusion weighting (i.e., b value). When
signal that is proportional to the rate of water motion. b = 0 s/mm2, there is no diffusion weighting, so the
This phenomenon is distinct from the static dephasing image displays only the effects of T2 weighting. As b is
that can be rephased by the 180-degree refocusing pulse. raised to 1,000 s/mm2, diffusion weighting increases,
In the brain, especially the white matter, diffusion of and signal from CSF (which has unrestricted diffusion)
water varies in all directions (anisotropic) rather than decreases. However, T2 weighting does not disappear
occurring to the same degree in all directions (isotropic) entirely, even at high b values, so the T2 signal may still
because diffusion occurs more easily parallel rather than appear within the image (T2 shine-through artifact) and
 Chapter 2 Magnetic Resonance Imaging as a Problem-Solving Tool 73

SECTION I
A B

C D
Figure 2-11 Diffusion-weighted imaging is more sensitive than noncontrast computed tomography (CT) or other magnetic resonance (MR)
imaging modalities for hyperacute ischemic stroke. A: Axial CT performed 30 minutes after the patient experienced ischemic symptoms during a
coronary angiogram shows no definite abnormality. B: Axial T2-weighted fluid-attenuated inversion recovery image from an MR scan initiated 15
minutes after the CT shows no acute abnormality. C: Axial diffusion-weighted imaging from the same MR scan reveals abnormal cortical hyper-
intensity in the anterior left perisylvian region (arrow). D: Corresponding apparent diffusion coefficient map confirms reduced diffusion in the
anterior left perisylvian cortex, consistent with a hyperacute left middle cerebral artery infarct (arrow).

make it difficult to determine whether the bright signal whereas areas with low ADC (slow diffusion) will be dark.
seen on DWI represents restricted diffusion, T2 prolon- Note that the signal intensities displayed on an ADC map
gation (T2 shine-through), or both in some proportion. are the inverse of what is seen on a diffusion-weighted
This difficulty is resolved by use of an apparent diffu- image: areas of restricted diffusion will appear bright on
sion coefficient (ADC) map, which the computer derives DWI but dark on the ADC map.
mathematically by comparing the diffusion-weighted Acute cerebral infarction is the most commonly
images obtained at two different b values (e.g., b = 0 s/mm2 encountered pathologic process to reduce diffusion
and b = 1,000 s/mm2). ADC is a measure of the rate of dif- (bright on DWI and dark on ADC), with MR findings
fusion, and the ADC map is a “pure diffusion map” free of seen as early as 30 minutes after ischemia onset, when it
T2 shine-through effects. On the ADC map, pixel intensity is not detectable by CT or by other types of MR sequences
corresponds directly to the ADC value itself, so areas with (Figure 2-11). Because the high DWI signal decreases
high ADC (rapid diffusion), such as CSF, will be bright, over the course of days to weeks, diffusion imaging is
74 Section I  Advanced Modalities: Protocols and Optimization

A B C
Figure 2-12 Diffusion-weighted imaging can differentiate acute from chronic ischemia. A: Axial T2-weighted spin-echo image in a patient with
endocarditis and new neurologic deficits shows numerous periventricular and subcortical white matter lesions of indeterminate acuity. B: Axial
diffusion-weighted imaging demonstrates hyperintensity in several of the subcortical lesions (arrows). C: Corresponding apparent diffusion coef-
ficient map confirms reduced diffusion in these lesions (arrows), consistent with acute embolic infarcts and not T2 shine-through on the diffusion-
weighted imaging from subacute or chronic ischemia.

also very helpful in distinguishing acute from chronic of the blood flow into the imaging plane with intact
ischemia (Figure 2-12). Reduced diffusion can also be longitudinal magnetization, they generate a bright MR
seen in pyogenic abscesses, epidermoid masses, her- signal known as flow-related enhancement.
pes encephalitis, Creutzfeldt-Jakob disease, and tumors TOF MRA can be performed by both 2D and 3D tech-
with high cellular density (e.g., lymphoma). Limitations niques. Two-dimensional TOF MRA has higher sensitivity
of DWI include susceptibility to field inhomogeneities, to slow blood flow than does 3D because 2D TOF imag-
particularly at tissue–air interfaces of the skull base, ing excites individual thin slices whereas 3D excites entire
adjacent to postsurgical metallic hardware, and at large slabs of tissue simultaneously. Because blood must travel
collections of blood breakdown products (Figure 2-13), a longer distance through a thicker slab with 3D imaging
leading to signal dropout and image distortion. than with 2D imaging, the blood experiences some satu-
An interesting application of DWI is diffusion ten- ration effects from successive RF pulses and loses some
sor imaging (DTI), which assesses diffusion in at least signal. The signal loss is particularly pronounced for 3D
six different directions. This yields a more complete set imaging of slowly moving blood. For that reason, 3D TOF
of diffusivity information that can be used to deduce MRA may fail to display vessels with slow flow. However,
axonal fiber orientation and thereby create 3D maps of 3D TOF MRA achieves thinner, contiguous imaging sec-
white matter tracts in the brain. tions and much higher spatial resolution than does 2D
TOF. Three-dimensional TOF is also less prone to signal
6. Time-of-Flight MR Angiography loss from turbulent blood flow within an area of stenosis,
To visualize the intracranial vasculature, time-of-flight so 3D TOF MRA is less likely to overestimate the severity of
(TOF) imaging is most commonly used. TOF imaging a stenosis. Cervical MRA for the carotid and vertebral arter-
provides an “MR angiogram” (MRA) of the circle of Wil- ies in the neck is typically performed with 2D TOF because
lis by (1) minimizing signal from stationary background 2D TOF is more sensitive for detecting slow flow within
tissues and (2) maximizing signal from flowing blood. an area of stenosis. Intracranial MRA of the circle of Willis
GRE sequences with a rapid succession of RF pulses is typically performed with 3D TOF imaging because 3D
and very short TR are used. If the TR is shorter than the TOF MRA provides better spatial resolution and depiction
T1 of background tissue, the rapid RF pulses prevent the of small distal cerebral arteries (Figure 2-14, A).
tissue spins from regaining their normal full longitudi-
nal magnetization. Because longitudinal magnetization 7. Contrast-Enhanced MRA
is reduced to a minimum, the next RF pulse produces Contrast-enhanced MRA is often used for evaluation of
less transverse magnetization, and the background tis- cervical vessels (Figure 2-14, B and C). A large coronal
sue appears dark. In this state, the background tissue is FOV can be used to image the vessels from their origins
described as saturated. Blood situated outside the imag- at the aorta to their vascular territories within the brain
ing slice, however, is relatively unaffected by the succes- in a fraction of the time required for conventional axial
sive RF pulses, retains its longitudinal magnetization, plane TOF MRA. Contrast-enhanced MRA also suffers
and remains unsaturated. When the unsaturated spins less signal loss secondary to slow or turbulent flow.
 Chapter 2 Magnetic Resonance Imaging as a Problem-Solving Tool 75

SECTION I
A B

C D
Figure 2-13 A: Axial T1-weighted spin echo shows hyperintensity in the splenium of the corpus callosum, compatible with hemorrhage.
B: Axial fluid-attenuated inversion recovery shows signal loss within the hemorrhage as well as bright signal in the sulci posteriorly suspicious for
subarachnoid hemorrhage. Increased signal is seen in the caudate body and along the body of the corpus callosum, with subtly increased signal in
the right posteromedial parietal and occipital lobes. C: Axial diffusion-weighted imaging more dramatically demonstrates high signal in the right
posterior parietal lobe, caudate body, and corpus callosum. This may reflects reduced diffusion due to acute infarction. Diffusion-weighted imag-
ing is prone to susceptibility effects, seen as signal loss within the hemorrhage. D: Apparent diffusion coefficient map shows reduced diffusion in
the right posterior cerebral artery territory and corpus callosum, consistent with acute infarction.

PITFALLS AND LIMITATIONS

OF MRI type of implant or device is documented to be MR com-
patible. Information regarding MR compatibility and
Use of MRI is limited in several important situations. The safety testing of thousands of specific objects can be
magnetic field can induce voltages or currents in electri- found online at www.MRIsafety.com. Cardiac pacemak-
cally conductive materials (wires, leads, implants), which ers and defibrillators are considered a contraindication
may result in heating. Patients with medical implants or to MR. Patients with these implanted devices should be
devices made of ferromagnetic materials (e.g., certain studied by MR only after specific evaluation of risks and
aneurysm clips) may be at risk for object displacement or benefits and after consideration of alternative means for
heating. MR should not be performed unless the specific obtaining the data needed for care. Such studies should
76 Section I  Advanced Modalities: Protocols and Optimization

A B C
Figure 2-14 Intracranial and cervical magnetic resonance angiography (MRA). A: Three-dimensional time-of-flight MRA of the circle of Willis
shows a tangle of vessels with enlarged right middle cerebral and lenticulostriate artery branches, consistent with arteriovenous malformation and
hemorrhage. B: Gadolinium-enhanced cervical MRA shows focal lobular irregularity (arrow) of the left internal carotid artery (cervico–petrous
junction), concerning for injury such as dissection with pseudoaneurysm. C: Given the concern for dissection, axial unenhanced T1-weighted fat-
saturated sequence was obtained, which shows crescentic high signal in the left internal carotid artery (arrow) consistent with methemoglobin in
an intramural hematoma due to acute arterial dissection.

be performed on a case-by-base basis and only if suffi- be used, and hemodialysis should be performed imme-
cient radiology and cardiology expertise is available. diately following the scan (if the patient is already on
MR can be performed at any stage of pregnancy, fol- dialysis). Patients with GFR greater than 60 ml/min/1.73
lowing thoughtful consideration of risks and benefits m2 need no special treatment, although gadodiamide
by appropriate attending radiologists, obstetricians, and should not be given in patients with any level of renal
perinatologists. Gadolinium-based contrast agents may disease.
be administered on a case-by-case basis but should not
be given routinely during pregnancy because their risks CURRENT RESEARCH AND
to the fetus are not known. (Because gadolinium-based
FUTURE DIRECTION
contrast agents can enter the amniotic fluid, there is
theoretical potential for dissociation of the toxic gado- MRI at 1.5 T is the current clinical standard, although
linium from its chelating compound and concern for there has been an increasing shift to 3-T imaging
theoretical risk of fetal injury.) Again, any decision to for clinical use in the past few years. Systems at field
administer gadolinium-based contrast should be pre- strengths of 7 T and higher are now under investigation
ceded by careful analysis of the risks and benefits by the but currently used only for research. The primary appeal
team of attending physicians. of 3-T over 1.5-T imaging is its better signal-to-noise
Much has been recently written about nephrogenic ratio. Field strength and MR signal are linearly related,
systemic fibrosis and its association with gadolinium- with twice the MR signal at 3 T than at 1.5 T for the same
based contrast agents in patients with severe renal dis- scan time. Figure 2-15 illustrates the utility of imaging at
ease. Nephrogenic systemic fibrosis refers to tissue higher field strength.
fibrosis with skin thickening and hardening as well as Higher field strengths prolong T1 recovery times
fibrosis of other body parts, including the heart, lung, but leave T2 relatively unaffected. This allows for
and skeletal muscles. It occurs following gadolinium- ­higher-quality TOF MRA images at 3 T compared to 1.5 T
based contrast administration in approximately 3% because the background is better suppressed at 3 T (less
to 5% of patients with severe renal disease. Although recovery of longitudinal magnetization), whereas inflow-
most published cases have been reported in patients ing, unsaturated blood has higher signal at 3 T (double
who received gadodiamide (Omniscan, GE Healthcare), the signal of 1.5 T). Longer T1 recovery times do result
nephrogenic systemic fibrosis has been associated with in poor tissue contrast between gray and white matter on
other gadolinium chelates, such as gadopentetate dime- T1-weighted SE or FSE/TSE sequences performed at 3 T
glumine (Magnevist, Bayer Schering) and gadoverset- if the same TR is used, but this can be avoided by using
amide (OptiMARK, Mallinckrodt). The most recent 2007 inversion-prepared sequences for T1 weighting. Higher
MR safety guidelines released by the American College of field strengths also have greater chemical shift effects,
Radiology recommend that patients with chronic renal allowing for more effective fat suppression but suffering
disease and glomerular filtration rates (GFR) less than 60 from more chemical shift artifacts if a greater bandwidth
ml/min/1.73 m2 not receive ­gadolinium-based contrast is not used. Susceptibility effects increase with field
unless the benefits of contrast clearly exceed the risks. In strength, so sequence parameters must be optimized to
those cases, the lowest possible dose necessary should decrease artifact.
 Chapter 2 Magnetic Resonance Imaging as a Problem-Solving Tool 77

SECTION I
A B

C D
Figure 2-15 Imaging at 3 T. A 29-year-old man with epilepsy reported to have “abnormal fluid-attenuated inversion recovery (FLAIR) signal in
the right parietal lobe” on prior outside magnetic resonance imaging presented for further workup. Imaging at 3 T demonstrates T2 prolongation
in the right parietal lobe on axial (A) and coronal (C) FLAIR. T1-weighted spoiled gradient recalled-echo (GRE) sequences, axial (B) and coronal
(D) planes, show that the abnormal T2 signal corresponds to a focal area of cortical thickening and blurring. This is suggestive of a cortical dys-
plasia that, although subtle, can be better delineated at 3 T due to its superior signal-to-noise ratio. The FLAIR and spoiled GRE sequences were
three-dimensional acquisitions to ensure thin, contiguous slices for detection of subtle abnormalities in this seizure patient.

One of the chief concerns with high-field imaging is the In parallel imaging, k-space is undersampled by
greater specific absorption rate (SAR), which is the energy decreasing the number of phase-encoding steps. This
absorbed by tissue following an RF pulse, potentially lead- reduces scan time. However, the resultant loss of spa-
ing to tissue heating. SAR quadruples when field strength tial information is recovered by taking advantage of the
is doubled from 3 to 1.5 T. SAR also increases with greater redundant spatial information provided by the phased-
flip angles and more RF pulses during a given TR, so SAR array coils used for parallel imaging. Because signal
is particularly high for FSE/TSE sequences where mul- strength varies according to distance from the receiver
tiple 180-degree pulses are given. Modifications to limit coil, spatial information afforded by differences in sig-
SAR include decreasing the flip angle or refocusing pulse nal strength at the receiver coil can be used to complete
(although this also decreases MR signal). The synergistic the dataset for the MR image. Undersampling k-space
and tandem development of parallel imaging techniques, reduces FOV, which produces severe aliasing in the MR
which reduce scan time and limit energy exposure, has image. However, mathematical models have been devel-
greatly facilitated imaging at 3 T. oped to correct for aliasing and produce a proper image;
78 Section I  Advanced Modalities: Protocols and Optimization

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Hashemi RH, Bradley Jr WG, Chen DY, et al. Suspected multiple sclerosis: Thomsen HS. European Society of Urogenital Radiology guidelines on contrast
MR imaging with a thin-section fast FLAIR pulse sequence. Radiology. media application. Curr Opin Urol. 2007;17(1):70-76.
1995;196(2):505-510. Warach S, Gaa J, Siewert B, Wielopolski P, Edelman RR. Acute human stroke
Kanal E, Barkovich AJ, Bell C, et al. ACR guidance document for safe MR studied by whole brain echo planar diffusion-weighted magnetic resonance
practices: 2007. AJR Am J Roentgenol. 2007;188(6):1447-1474. imaging. Ann Neurol. 1995;37(2):231-241.
Kuo PH, Kanal E, Abu-Alfa AK, Cowper SE. Gadolinium-based MR contrast Webb JA, Thomsen HS, Morcos SK. The use of iodinated and gadolinium
agents and nephrogenic systemic fibrosis. Radiology. 2007;242(3): contrast media during pregnancy and lactation. Eur Radiol.
647-649. 2005;15(6):1234-1240.
 chapter 3

Advanced MR (MR Spectroscopy,

Diffusion Imaging, Diffusion
Tensor Imaging, and Perfusion
Imaging): A Multiparametric
Algorithmic Approach to Problem
Solving in Neuroradiology
Meng Law, Saulo Lacerda, and Pascal Bou-Haidar

INTRODUCTION
As ­mentioned, most of these lesions can present with
Neuroradiology has progressed rapidly in recent times “apparent” elevation of Cho (relative to NAA or Cr),
to be in the forefront of imaging technology. Advanced decrease in NAA, and elevation of lipids and lactate.
magnetic resonance imaging (MRI) techniques, such When Cho in the pathologic voxels is compared with
as magnetic resonance spectroscopy (MRS), diffusion- Cho in the contralateral normal brain tissue [Cho(n)],
weighted imaging (DWI), diffusion tensor imaging, and in some of cases total Cho is, in fact, reduced com-
perfusion MRI techniques can give important in vivo pared to the normal side.
physiologic and metabolic information, complement-
ing morphologic findings from conventional MRI in the Diffusion-Weighted and Diffusion
clinical setting. Combining these new tools can help in
Tensor Imaging
solving difficult cases and increase diagnostic specificity
and confidence. Water molecules undergo random brownian diffusion
over time due to differences in concentration according
IMAGING TECHNIQUES to Fick’s law. Although diffusion is a random process,
directional preference may result from local barriers;
Magnetic Resonance Spectroscopy for example, barriers to diffusion in white matter tracts
include axonal proteins and myelin. DWI has been
The basic metabolite changes common to brain instrumental in the early diagnosis of acute ischemic
pathology include elevations in choline (Cho), lactate, stroke. More recently, restricted diffusion has been dem-
and lipids, and decreases in N-acetylaspartate (NAA) onstrated in very cellular gliomas and lymphomas. We
and creatine (Cr) (Figure 3-1). As clinical spectroscopy will apply these diffusion changes in the characteriza-
becomes more sophisticated, metabolites identified by tion of brain and spinal cord lesions.
short echo time (TE) MRS are becoming important in Several reports have shown that glioma grade cor-
increasing the specificity of MRS in brain tumor diag- relates inversely with minimum apparent diffusion
nosis. The increase in Cho in simple terms is attrib- coefficient (ADC), likely the result of increasing tumor
uted to cell membrane turnover and proliferation. To cellularity with grade. Although the initial reports on
determine whether elevation in Cho is pathologic and, correlation between minimum ADC and glioma grade
more importantly, to increase specificity, the more have shown promise, the role of DWI in preoperative
optimal approach involves comparing Cho in the assessment of glioma grade is controversial and remains
pathologic voxels with Cho in the contralateral nor- investigational because of substantial overlap in ADC
mal brain tissue, the so-called normalized Cho levels. values among different grades of glioma. The finding of
This method may be useful in the clinical setting of abnormally reduced diffusion in, around, and remote
focally enhancing lesions for characterizing inflam- from the resection bed immediately after surgery for
matory, ischemic, demyelinating, and tumoral lesions. brain tumor resection is not uncommon. The important

79
80 Section I  Advanced Modalities: Protocols and Optimization

A C
Figure 3-1 A: Normal spectra acquired at different echo times demonstrating normal concentrations of choline (Cho), creatine (Cr), and
N-acetylaspartate (NAA). The relative concentration (e.g., Cho/Cr or Cho/NAA) of each of the metabolites is different at different echo times
because of the differences in T2 relaxation time for different metabolites. This is a pitfall when comparing metabolite ratios at different echo times.
B: Localizing postcontrast T1-weighted image demonstrating a mass with the location of the blue voxel. C: Abnormal spectrum within a recurrent
glioma demonstrating marked elevation in Cho relative to Cr and NAA. (Courtesy Nouha Salibi, Siemens Medical Solutions.)

clinical implication is that these areas of immediate that may generate three-dimensional representations
postoperative diffusion abnormality invariably undergo of axonal fibers, or three-dimensional fiber tractography.
a phase of contrast enhancement on routine anatomic These algorithms in effect attempt to “string together”
images that easily can be misinterpreted as tumor recur- adjacent voxels based on similarity in the direction of
rence and as early treatment failure, prompting aggres- their major eigenvectors (Figure 3-3).
sive therapy with high potential for toxicity. These areas Although useful in tract visualization, white matter
of enhancement invariably evolve into encephalomala- fiber tractography represents a more postprocessed rep-
cia or gliotic cavity on long-term follow-up studies (Fig- resentation of diffusion tensor imaging data compared
ure 3-2), indicating the occurrence of some immediate to visualization of tensor maps and maps of fractional
postoperative ischemia from either surgical retraction or anisotropy and mean diffusivity metrics; therefore, it
venous insufficiency. is prone to the addition of error. In voxels that con-
Diffusion tensor imaging is the application of DWI tain crossing fiber tracts from two or more directions,
in six or more directions. This allows the calculation of the association between diffusion tensor measurement
fractional anisotropy, relative anisotropy, mean diffusiv- and axonal fiber direction is less direct. Algorithms have
ity, and the major and minor eigenvalues, which can be been developed to mitigate this problem, which arises
color coded. Colors are assigned as blue = superoinfe- commonly in central nervous system (CNS) structures
rior orientation; green = anteroposterior; and red = lat- such as the brainstem and in areas with complex cross-
erolateral (Figure 3-3). ing association fibers. High angular resolution diffu-
In white matter, the direction of the major eigenvector sion tensor imaging techniques have been developed in
tends to be parallel with the orientation of axonal fibers. an effort to resolve the crossing fibers in the brain and
Using this observation, algorithms have been developed brainstem. Various data smoothing and interpolation
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 81

SECTION I
A B

Figure 3-2 A 52-year-old-man with glio-

blastoma multiforme in the right occipital
lobe. A: Axial T1-weighted image postcon-
trast showing a mass with heterogeneous
enhancement in the occipital lobe. B: Axial
T1-weighted image postcontrast on the
first postoperative day demonstrating radi-
cal resection of the tumor. C, D: Diffusion
apparent diffusion coefficient maps show-
C D ing diffusion restriction areas along the
margin of the surgical cavity (arrows).
Continued
82 Section I  Advanced Modalities: Protocols and Optimization

E F

Figure 3-2—cont’d E, F: Postcontrast

T1-weighted image demonstrating enhance-
ment 1 month after initial surgery. The
enhancement relates to transient opera-
tive ischemia rather than recurrent tumor.
G: Diffusion-weighted image demonstrat-
ing resolution of the ischemic findings.
H: Almost complete resolution of the
enhancing regions at a later time interval.
G H

techniques also have been used to minimize the propa- lower signal-to-noise ratio, and the kinetic modeling
gation of noise error. algorithms for the estimation of blood volume and vas-
cular permeability are more complex. Here we discuss
Perfusion Imaging Dynamic both techniques and show how characterization of sig-
Susceptibility Contrast Perfusion nal intensity curves using both DSC MRI and DCE MRI
MRI and Dynamic Contrast- techniques can be useful in problem solving, particu-
larly in addressing difficult questions such as differen-
Enhanced MRI
tiating recurrent tumoral disease from therapy-related
Perfusion MRI (with diffusible contrast) can be per- necrosis.
formed using two major techniques. Dynamic suscep-
tibility contrast perfusion magnetic resonance imaging Technical Pitfalls and Limitations in DSC MRI
(DSC MRI), which utilizes a first-pass T2*-weighted Even though DSC MRI is the most commonly used
technique, is most commonly distributed by the major and easily applied technique for studying brain tumor
MRI vendors and is used more frequently. Dynamic con- perfusion, use of a gradient echo sequence is associ-
trast-enhanced magnetic resonance imaging (DCE MRI) ated with a number of important limitations. First,
is a steady-state T1-weighted technique that is not com- because the technique is weighted to measure suscep-
monly used because the T1 technique yields a slightly tibility, it is extremely sensitive to lesions that cause
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 83

SECTION I
A B

C D

E F G
Figure 3-3 Patient with adrenoleukodystrophy. A–C: Axial T2-weighted, FLAIR, and postcontrast T1-weighted images demonstrating the typi-
cal regions of demyelination involving the posterior periventricular white matter. B: Magnitude and directional color-coded fractional anisotropy
(FA) maps from diffusion tensor imaging (DTI) demonstrating a marked decrease in FA in the posterior periventricular white matter. C, D: Color-
coded fiber tractography demonstrating a decrease in the projected fiber tracts in the posterior white matter. E, F: Postcontrast T1-weighted, gray
scale and color FA maps demonstrating regions of interest for quantitation of FA show a marked decrease in FA in the posterior white matter
compared with the anterior white matter. This case illustrates how DTI data can be presented.

magnetic field inhomogeneity, such as blood products, choroids plexus tumors, and meningiomas. Therefore,
calcium, bone, melanin, metals, and lesions near the extremely low or high ­perfusion values must be con-
brain–bone–air interface, such as the skull base. This sidered with caution. Correction algorithms can be
factor becomes important when characterizing both applied to compensate for leakiness. When T1 effects
high-grade gliomas, which may contain blood prod- are exaggerated, relative cerebral blood volume (rCBV)
ucts, and low-grade gliomas, which may contain some will be underestimated, which may affect tumor grade
calcification. Solutions for reducing inhomogeneity prediction. Preloading with a small dose of contrast
and susceptibility include decreasing slice thickness, (which can also serve to produce T1 steady-state per-
which also reduces the signal-to-noise ratio and slice meability maps) along with gamma variate and linear
coverage. Parallel imaging methods also can reduce fitting to correct for the leakage will improve the accu-
both susceptibility and scan time, thus allowing more racy of rCBV estimations. Where T2* effects are exagger-
brain coverage and a higher signal-to-noise ratio. If a ated in the setting of a very leaky lesion, rCBV will be
larger lesion requires increased brain coverage, then overestimated. Hence, correction algorithms can result
the interslice gap can be increased while maintaining in either an increase or a decrease in rCBV (Figure 3-4).
thinner slices to reduce susceptibility. Second, quan- Finally, some controversy still exists regarding the effect
tification of perfusion metrics, such as cerebral blood of corticosteroid/dexamethasone administration on
volume (CBV) and vascular permeability (Ktrans), can perfusion and permeability estimations in the brain.
be inaccurate in lesions having a very leaky blood– Anecdotally and physiologically, it appears that steroid
brain barrier, such as glioblastoma multiforme (GBM), significantly reduces vascular permeability; however, in
84 Section I  Advanced Modalities: Protocols and Optimization

A B C

D E
Figure 3-4 Heterogeneously enhancing right temporal high-grade glioma in a 50-year-old man. A: Axial T1-weighted image showing an enhanc-
ing mass in the right temporal region. B: Dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC MRI) uncorrected relative
cerebral blood volume (rCBV) color overlay demonstrating elevated rCBV. C: DSC MRI corrected rCBV color overlay demonstrating decrease in
rCBV. DSC MRI T2* signal intensity curves demonstrating increased leakiness as well as exaggerated T2* effect of gadolinium resulting in overes-
timation of rCBV. D, E: Overestimation and underestimation can be corrected by preloading with contrast as well as applying a linear or gamma
variate fit that will produce corrected rCBV maps that provide a more accurate estimation of rCBV. Bottom row: Dynamic contrast-enhanced
magnetic resonance imaging permeability map demonstrating increased vascular permeability.
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 85

terms of perfusion metrics, a recent paper seems to sug-

SECTION I
Intraaxial brain mass
gest that dexamethasone does not significantly affect
tumor blood flow, blood volume, or transit time but
may, by reducing peritumoral water content and local Conventional CE MRI
tissue pressure, subtly increase perfusion in the edema- Does the lesion enhance?
tous brain.
No Yes

PROBLEM SOLVING IN BRAIN TUMORS Magnetic resonance Diffusion magnetic

spectroscopy resonance imaging
Is there elevation of Is diffusing facilitated
Multiparametric Algorithmic Cho/NAA over 2.2? over 1.1/100 mm2/ADC?
Approach
No Yes Yes No
The ring-enhancing mass lesion in the brain can have
a number of differential diagnoses. They include high-
grade glioma, metastasis, infarct, radiation necro- Low grade Is there necrosis
neoplasm or on CE MRI?
sis, abscess, or tumefactive demyelinating lesion. An Encephalitis
algorithmic multiparametric approach combining Yes No
findings from each of the advanced MRI techniques
can be used to differentiate these pathologies (Figure Perfusion magnetic Lymphoma
3-5). A potential approach to a mass lesion would ini- resonance imaging
tially be evaluation to determine whether the lesion Is perfusion increased
over 1.75 r/CBV?
enhanced. If enhancement is seen, then review the
DWI. If ADC is low, then consider CNS lymphoma.
If ADC is higher, then review the perfusion imaging. No Yes Yes No
If rCBV (perfusion) is less than 1.75, then consider an
Low grade High grade TDL or abscess
abscess or tumefactive demyelinating lesion. If rCBV neoplasm neoplasm Abscess
is greater than 1.75, then consider either a high-grade
glioma or metastasis. Review of the rCBV in the perien-
hancement T2 signal abnormality will help differen- Magnetic resonance spectroscopy
tiate between an infiltrating high-grade glioma and a Is there perienhancement infiltration
well-circumscribed metastasis. over 1 Cho/NAA?
Figures 3-6 to 3-16 show 10 illustrative cases of
how these imaging techniques are applied to prob- No Yes
lem solving. In clinical practice, this is done on an Metastasis High grade glioma
ad hoc basis for each case. The algorithm provides a
more structured approach that can benefit both the Figure 3-5 Flowchart illustrating order of methods used to diag-
novice and the more experienced neuroradiologist in nose and differentiate intraaxial masses. Each method provides an
answer to a specific question, which is used as a discriminator to dis-
problem solving. We review a number of problematic tinguish lesions. 1.1/100 mm2/ADC, 1.1 × 10–3 mm2/s; ADC, apparent
cases and, based on the algorithm, demonstrate how diffusion coefficient; CE, contrast material enhanced; Cho, choline;
a multiparametric algorithmic technique can be used NAA, N-acetylaspartate; r/CBV, relative cerebral blood volume; TDL,
in the clinical setting. We also highlight some impor- tumefactive demyelinating lesion. (From Al-Okaili RN, Krejza J,
tant teaching points that will help to increase accuracy Woo JH, et al. Intraaxial brain masses: MR imaging-based diagnostic
strategy—Initial experience. Radiology 2007;243(2):539-550.)
when using this algorithm.

Perfusion and Tumor Vascularity

This case illustrates an important pitfall in terms of per- DWI and Tumor Cellularity
fusion of low-grade oligodendrogliomas. The typical DWI can demonstrate areas of high cellularity indicated
signs found on conventional images are characterized by low ADC values. Figure 3-10 shows a typical example
by heterogeneous cortically based tumors, with vari- of a high-grade glioma, which not uncommonly can
able enhancement. Foci of calcifications may be seen present with areas of very low ADC levels, probably
on MRI or computed tomography. However, perfusion related to its high cellularity. In these cases, following
imaging often is elevated in low-grade oligodendro- the algorithm, other findings such as high capillary den-
gliomas (Figure 3-7). Law et al. reviewed 160 glioma sity within areas of T2 hyperintensity suggest a primary
patients and found sensitivity of 95% and specificity high-grade glioma over lesions such as a lymphoma,
of 57.5% for differentiating high-grade from low-grade which may have decreased ADC because of cellularity
gliomas. In Figure 3-8, all of the conventional imag- but does not tend to have very high perfusion.
ing findings and the spectroscopic ratios favor a high- Typically, infective or inflammatory lesions are
grade glioma; the perfusion study demonstrates high known as “cold lesions,” although investigators have
capillary density compatible with a high-grade tumor. demonstrated increased rCBV and vascular endothe-
This situation illustrates a pitfall of this algorithm and lial growth factor (VEGF) expression in the capsule of
seems to undermine the role of DSC MRI in glioma bacterial abscesses, which probably are responsible for
grading. the high perfusion along the edge of the lesion. Thus,
86 Section I  Advanced Modalities: Protocols and Optimization

Intraaxial brain mass

Conventional CE MRI
Does the lesion enhance?
Question 1
No Yes
Question 7 Question 2
Magnetic resonance Diffusion magnetic
spectroscopy resonance imaging
Is there elevation of Is diffusion facilitated
Cho/NAA over 2.2? over 1.1/100 mm2/ADC?

No Yes Yes No

Question 4
Question 8
Low grade Is there necrosis
Question 3
neoplasm or on CE MRI?
Encephalitis
Yes No

Perfusion magnetic Lymphoma

resonance imaging
Is perfusion increased Question 6
over 1.75 r/CBV?

A B No Yes Yes No

Low grade High grade TDL or abscess

neoplasm neoplasm Abscess
Question 5

Magnetic resonance spectroscopy

Is there perienhancement infiltration
over 1 Cho/NAA?

No Yes

Metastasis High grade glioma

C D

E F G
Figure 3-6 A 41-year-old woman with a history of headaches demonstrating a low grade-glioma (LGG) that follows all the magnetic resonance
findings for an LGG. A: Axial T1-weighted image showing a mass within the right perirolandic region with no enhancement. B: Axial FLAIR image
demonstrating the right perirolandic region mass with hyperintensity but minimal edema. C–E: Magnetic resonance spectroscopy demonstrating no
increase in choline, even compared to choline in contralateral normal brain (purple spectra), in keeping with LGG. F: Gradient-echo axial dynamic
susceptibility contrast T2* magnetic resonance imaging with relative cerebral blood volume color overlay demonstrating reduced relative cerebral
blood volume within the lesion. G: Spin-echo dynamic contrast-enhanced T1 magnetic resonance image showing a decrease in vascular permeability.
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 87

SECTION I
Intraaxial brain mass

Conventional CE MRI
Does the lesion enhance?
Question 1
No Yes
Question 7 Question 2
Magnetic resonance Diffusion magnetic
spectroscopy resonance imaging
Is there elevation of Is diffusion facilitated
Cho/NAA over 2.2? over 1.1/100 mm2/ADC?

No Yes Yes No

Question 4
Question 8
Low grade Is there necrosis
Question 3
neoplasm or on CE MRI?
Encephalitis
Yes No

A B Perfusion magnetic Lymphoma

resonance imaging
Is perfusion increased Question 6
over 1.75 r/CBV?

No Yes Yes No

Low grade High grade TDL or abscess

neoplasm neoplasm Abscess
Question 5

Magnetic resonance spectroscopy

Is there perienhancement infiltration
over 1 Cho/NAA?

No Yes

Metastasis High grade glioma

C

D E
Figure 3-7 A 45-year-old woman with a history of headaches. Example of nonenhancing low-grade oligodendroglioma with high perfusion.
A: Axial FLAIR image showing a mass in the left frontal lobe. B: Contrast-enhanced axial T1-weighted image demonstrating no contrast enhance-
ment. C, D: Magnetic resonance spectroscopy demonstrating minimal increase in choline, in keeping with a low-grade glioma. E: Gradient-echo
axial dynamic susceptibility contrast perfusion magnetic resonance imaging with relative cerebral blood volume color overlay demonstrating
slightly elevated cerebral blood volume within the lesion. As a pitfall this was found to be an oligodendroglioma, a tumor known to have high
cerebral blood volume levels even when low grade.
88 Section I  Advanced Modalities: Protocols and Optimization

Intraaxial brain mass

Conventional CE MRI
Does the lesion enhance?
Question 1
No Yes
Question 7 Question 2
Magnetic resonance Diffusion magnetic
spectroscopy resonance imaging
Is there elevation of Is diffusion facilitated
Cho/NAA over 2.2? over 1.1/100 mm2/ADC?

No Yes Yes No
A B

Question 4
Question 8
Low grade Is there necrosis
Question 3
neoplasm or on CE MRI?
Encephalitis
Yes No

Perfusion magnetic Lymphoma

resonance imaging
Is perfusion increased Question 6
over 1.75 r/CBV?

No Yes Yes No

Low grade High grade TDL or abscess

neoplasm neoplasm Abscess
C D
Question 5

Magnetic resonance spectroscopy

Is there perienhancement infiltration
over 1 Cho/NAA?

No Yes

Metastasis High grade glioma

E
Figure 3-8 Nonenhancing high-grade glioma with low choline but high relative cerebral blood volume (rCBV) in a 59-year-old man with
pathology-proven anaplastic astrocytoma. A: Axial FLAIR image demonstrating a hyperintense right parietal tumor. B: Axial T1-weighted image
showing no contrast enhancement. C, D: Magnetic resonance spectroscopy demonstrating a moderate increase in choline levels. E: Gradient-echo
axial dynamic susceptibility contrast perfusion magnetic resonance imaging with rCBV color overlay demonstrating increased relative cerebral
blood volume within the lesion, in keeping with the diagnosis of anaplastic astrocytoma (World Health Organization grade III).
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 89

SECTION I
Intraaxial brain mass

Conventional CE MRI
Does the lesion enhance?
Question 1
No Yes
Question 7 Question 2
Magnetic resonance Diffusion magnetic
spectroscopy resonance imaging
Is there elevation of Is diffusion facilitated
Cho/NAA over 2.2? over 1.1/100 mm2/ADC?

No Yes Yes No

A B
Question 4
Question 8

Low grade Is there necrosis

Question 3
neoplasm or on CE MRI?
Encephalitis
Yes No

Perfusion magnetic Lymphoma

Question 6
resonance imaging
Is perfusion increased
over 1.75 r/CBV?

No Yes Yes No

Low grade High grade TDL or abscess

neoplasm neoplasm Abscess C D
Question 5

Magnetic resonance spectroscopy

Is there perienhancement infiltration
over 1 Cho/NAA?

No Yes

Metastasis High grade glioma

E F
Figure 3-9 Typical advanced magnetic resonance findings for a high-grade glioma in a 62-year-old man with a history of behavioral changes.
A: Axial T1-weighted image showing a mass with central necrosis and predominantly peripheral enhancement. B: Diffusion-weighted image
demonstrating no diffusion restriction, unlikely to be lymphoma. C: Gradient-echo axial dynamic susceptibility contrast perfusion mag-
netic resonance imaging with relative cerebral blood volume (rCBV) color overlay demonstrating marked increase in rCBV within the lesion.
D–F: Magnetic resonance spectroscopy of the peritumoral region showing increased choline, compatible with an infiltrating high-grade tumor
(World Health Organization grade IV).
90 Section I  Advanced Modalities: Protocols and Optimization

Intraaxial brain mass

Conventional CE MRI
Does the lesion enhance?
Question 1
No Yes
Question 7 Question 2
Magnetic resonance Diffusion magnetic
spectroscopy resonance imaging
Is there elevation of Is diffusion facilitated
Cho/NAA over 2.2? over 1.1/100 mm2/ADC?

No Yes Yes No

Question 4
Question 8
Low grade Is there necrosis
Question 3
neoplasm or on CE MRI?
Encephalitis
Yes No

Perfusion magnetic Lymphoma

resonance imaging
Is perfusion increased Question 6
over 1.75 r/CBV?

No Yes Yes No

Low grade High grade TDL or abscess

neoplasm neoplasm Abscess
A Question 5

Magnetic resonance spectroscopy

Is there perienhancement infiltration
over 1 Cho/NAA?

No Yes

Metastasis High grade glioma

C D E F
Figure 3-10 A high-grade glioma in a 62-year-old man with a history of behavioral changes. The remainder of the advanced magnetic reso-
nance imaging was able to problem solve and make an accurate diagnosis. A: Axial T1-weighted image showing a mass in the right thalamus with
heterogeneous enhancement and minimal central necrosis. B: Apparent diffusion coefficient (ADC) map demonstrating some areas with low
ADC values, suggesting central nervous system lymphoma or a glioma with high cellularity. C: Gradient-echo axial dynamic susceptibility contrast
perfusion magnetic resonance imaging (DSC MRI) with relative cerebral blood volume (rCBV) color overlay demonstrating increased rCBV within
the lesion. D, E: Magnetic resonance spectroscopy of the peritumoral region showing increased choline, compatible with an infiltrating high-grade
tumor (World Health Organization grade IV). F: Gradient-echo axial DSC MRI with rCBV color overlay demonstrating increased rCBV within the
peritumoral region, again suggesting infiltration by the tumor.
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 91

SECTION I
Intraaxial brain mass

Conventional CE MRI
Does the lesion enhance?
Question 1
No Yes
Question 7 Question 2
Magnetic resonance Diffusion magnetic
spectroscopy resonance imaging
Is there elevation of Is diffusion facilitated
Cho/NAA over 2.2? over 1.1/100 mm2/ADC?

No Yes Yes No

Question 4
Question 8
Low grade Is there necrosis
Question 3
neoplasm or on CE MRI?
Encephalitis
Yes No

Perfusion magnetic Lymphoma

resonance imaging
Is perfusion increased Question 6
over 1.75 r/CBV?

No Yes Yes No
A
Low grade High grade TDL or abscess
neoplasm neoplasm Abscess
Question 5

Magnetic resonance spectroscopy

Is there perienhancement infiltration
over 1 Cho/NAA?

No Yes

Metastasis High grade glioma

C D E
Figure 3-11 A 48-year-old man with a history of right hemiparesis. A: Axial T2-weighted showing a lesion in the left perirolandic region.
B: Postcontrast axial T1-weighted image demonstrating minimal, if any, contrast enhancement. C, D: Magnetic resonance spectroscopy demon-
strating increase in choline levels (Cho/N-acetylaspartate >2.2) within the lesion. E: Gradient-echo axial dynamic susceptibility contrast perfusion
magnetic resonance imaging with relative cerebral blood volume (rCBV) color overlay demonstrating significant elevation in rCBV (>1.75) within
the lesion, compatible with the diagnosis of fibrillary astrocytoma (World Health Organization grade III).
92 Section I  Advanced Modalities: Protocols and Optimization

Intraaxial brain mass

Conventional CE MRI
Does the lesion enhance?
Question 1
No Yes
Question 7 Question 2
Magnetic resonance Diffusion magnetic
spectroscopy resonance imaging
Is there elevation of Is diffusion facilitated
Cho/NAA over 2.2? over 1.1/100 mm2/ADC?

No Yes Yes No

Question 4
Question 8
Low grade Is there necrosis
Question 3
neoplasm or on CE MRI?
Encephalitis
Yes No

Perfusion magnetic Lymphoma

A resonance imaging
Is perfusion increased Question 6
over 1.75 r/CBV?

No Yes Yes No

Low grade High grade TDL or abscess

neoplasm neoplasm Abscess
Question 5

Magnetic resonance spectroscopy

Is there perienhancement infiltration
over 1 Cho/NAA?

No Yes

Metastasis High grade glioma

B

C D E F
Figure 3-12 Advanced magnetic resonance findings of a metastasis in a 48-year-old man with a history of breast cancer and right hemipa-
resis. A: Axial T1-weighted image showing a mass in the left frontoparietal operculum with ring enhancement and minimal central necrosis.
B: Diffusion-weighted image demonstrating no restriction diffusion within the lesion. C: Gradient-echo axial dynamic susceptibility contrast
perfusion magnetic resonance imaging (DSC MRI) with relative cerebral blood volume (rCBV) color overlay demonstrating increased rCBV within
the lesion. D, E: Magnetic resonance spectroscopy of the peritumoral region showing no increased choline, in keeping with the pathophysiol-
ogy of the peritumoral region in metastatic lesions. The region contains no infiltrating tumor cells and shows almost purely vasogenic edema.
F: Gradient-echo axial DSC MRI with rCBV color overlay demonstrating decreased rCBV within the peritumoral region, again compatible with
vasogenic edema.
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 93

SECTION I
Intraaxial brain mass

Conventional CE MRI
Does the lesion enhance?
Question 1
No Yes
Question 7 Question 2
Magnetic resonance Diffusion magnetic
spectroscopy resonance imaging
Is there elevation of Is diffusion facilitated
Cho/NAA over 2.2? over 1.1/100 mm2/ADC?

No Yes Yes No

Question 4
Question 8
Low grade Is there necrosis
Question 3
neoplasm or on CE MRI?
Encephalitis
Yes No

Perfusion magnetic Lymphoma

resonance imaging
Is perfusion increased Question 6
over 1.75 r/CBV?

No Yes Yes No

Low grade High grade TDL or abscess

neoplasm neoplasm Abscess

Question 5

Magnetic resonance spectroscopy

Is there perienhancement infiltration
over 1 Cho/NAA?

No Yes

Metastasis High grade glioma

A B C
Figure 3-13 Periventricular lesion compatible with central nervous system lymphoma in an immunocompetent 74-year-old woman with a history of
headaches. A: Axial T2-weighted image showing a mildly hyperintense mass in the isthmus of the cingulum on the right, surrounded by significant edema.
B: Axial T1-weighted image showing homogeneous enhancement of the mass suggestive of either a glioma or lymphoma. C: Apparent diffusion coeffi-
cient (ADC) map demonstrating significantly low ADC values, suggesting an lesion with high cellularity. Based on the algorithm, the absence of necrosis
suggests lymphoma as the most probable diagnosis, which was confirmed by biopsy. Lymphoma can be necrotic in an immunosuppressed patient.
94 Section I  Advanced Modalities: Protocols and Optimization

Intraaxial brain mass

Conventional CE MRI
Does the lesion enhance?
Question 1
No Yes
Question 7 Question 2
Magnetic resonance Diffusion magnetic
spectroscopy resonance imaging
Is there elevation of Is diffusion facilitated
Cho/NAA over 2.2? over 1.1/100 mm2/ADC?

No Yes Yes No

Question 4
Question 8
Low grade Is there necrosis
Question 3
neoplasm or on CE MRI?
Encephalitis
Yes No

Perfusion magnetic Lymphoma

resonance imaging
Is perfusion increased Question 6
over 1.75 r/CBV?

No Yes Yes No

Low grade High grade TDL or abscess

neoplasm neoplasm Abscess
Question 5

Magnetic resonance spectroscopy

Is there perienhancement infiltration
over 1 Cho/NAA?

No Yes

Metastasis High grade glioma

B C D
Figure 3-14 A 55-year-old-man with a tumefactive demyelinating lesion (TDL). A, B: Postcontrast T1-weighted images (coronal and axial)
demonstrating an incomplete ring of enhancement that is often seen in TDLs. C: Apparent diffusion coefficient map demonstrating no evidence of
diffusion restriction within the lesion, although some diffusion restriction is seen, possibly from acute demyelination, on the leading edge of the
lesion. D: Gradient-echo axial dynamic susceptibility contrast perfusion magnetic resonance imaging with relative cerebral blood volume color
overlay demonstrating reduced perfusion/vascularity within the lesion, even at the enhancing so-called leading edge.
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 95

SECTION I
Intraaxial brain mass

Conventional CE MRI
Does the lesion enhance?
Question 1
No Yes
Question 7 Question 2
Magnetic resonance Diffusion magnetic
spectroscopy resonance imaging
Is there elevation of Is diffusion facilitated
Cho/NAA over 2.2? over 1.1/100 mm2/ADC?

No Yes Yes No

Question 4
Question 8
Low grade Is there necrosis
Question 3
neoplasm or on CE MRI?
Encephalitis
Yes No

Perfusion magnetic Lymphoma

resonance imaging
Is perfusion increased Question 6
over 1.75 r/CBV?

No Yes Yes No

Low grade High grade TDL or abscess

neoplasm neoplasm Abscess
Question 5

Magnetic resonance spectroscopy

Is there perienhancement infiltration
over 1 Cho/NAA?

No Yes

Metastasis High grade glioma

A B C D
Figure 3-15 A 47-year-old man with a history of tooth extraction, who presented with fever and left hemiparesis. A: Mass with central necrosis
and ring enhancement in the right frontal region. B, C: Diffusion-weighted imaging with apparent diffusion coefficient map demonstrating diffu-
sion restriction in the center of the lesion. Considerable vasogenic edema is seen. D: Gradient-echo axial dynamic susceptibility contrast perfusion
magnetic resonance imaging with relative cerebral blood volume (rCBV) color overlay demonstrating reduced rCBV within the lesion. Advanced
magnetic resonance imaging findings are in keeping with a bacterial abscess.
96 Section I  Advanced Modalities: Protocols and Optimization

Intraaxial brain mass

Conventional CE MRI
Does the lesion enhance?
Question 1
No Yes
Question 7 Question 2
Magnetic resonance Diffusion magnetic
spectroscopy resonance imaging
Is there elevation of Is diffusion facilitated
Cho/NAA over 2.2? over 1.1/100 mm2/ADC?

No Yes Yes
No

Question 4
Question 8
Low grade Is there necrosis
Question 3
neoplasm or on CE MRI?
Encephalitis
Yes No

Perfusion magnetic Lymphoma

resonance imaging
Is perfusion increased Question 6
over 1.75 r/CBV?

No Yes Yes No

Low grade High grade TDL or abscess

neoplasm neoplasm Abscess
Question 5

Magnetic resonance spectroscopy

Is there perienhancement infiltration
over 1 Cho/NAA?

No Yes

Metastasis High grade glioma

A

B C D
Figure 3-16 A 52-year-old man with a history of colon cancer, who presented with altered conscious state. A: Postcontrast T1-weighted image
demonstrating a left thalamic mass with central necrosis and ring enhancement. B, C: Diffusion-weighted imaging and apparent diffusion coef-
ficient map demonstrating diffusion restriction in the center of the lesion suggesting a bacterial abscess. D: Gradient-echo axial dynamic suscep-
tibility contrast perfusion magnetic resonance imaging with relative cerebral blood volume (rCBV) color overlay demonstrating increased rCBV
within the edge of the lesion.
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 97

ALGORITHMIC-MULTIPARAMETRIC APPROACH

SECTION I
Glioma TDL
Cho/Cho(n) and CBV high Cho/Cho(n) and CBV low

High Venous
peritumoral structures
CBV/Cho

Glioma Non
Mets surgical

Low No venous
peritumoral structure
CBV/Cho

Infarct Delayed MTT/high CBV

Infarct/radiation
Radiation Low CBV/permeability abscess/
encephalitis
Mets Abscess DWI/MRS amino acids

Figure 3-17 An alternate algorithm that incorporates normalized Cho/Cho(n) and relative cerebral blood volume levels as well as perfusion
metrics such as mean transit time and vascular permeability. CBV, Cerebral blood volume; Cho, choline; DWI/MRS, diffusion-weighted imaging/
magnetic resonance imaging; MTT, mean transit time; TDL, tumefactive demyelinating lesion.

care should be taken when dealing with a focal lesion found in an ­infiltrating high-grade glioma. If rCBV and
having restricted diffusion and high rCBV levels. Using Cho are low, then consider a circumscribed metastasis
the algorithm, this lesion would be classified as a high- (Figure 3-12).
grade neoplasm. Figure 3-16 shows another pitfall in
this algorithm in that some infective bacterial abscesses Infiltrating and Well-Circumscribed Gliomas
may demonstrate increased perfusion. Pathologically, some high-grade gliomas are well cir-
cumscribed lesions with minimal tumor infiltration in
Alternate Multiparametric the peritumoral edema (Figure 3-19). These so-called
circumscribed gliomas are uncommon but represent
Algorithmic Approach
a potential pitfall in investigating peritumoral edema
An alternate multiparametric algorithmic approach when differentiating a primary glioma from a metastasis
that differs slightly from the algorithm shown in ­Figure using perfusion and MRS.
3-5 uses normalized metabolite ratios and perfusion
metrics such as mean transit time and time to peak. Tumefactive Demyelinating Lesions
The algorithm also incorporates vascular permeability When reviewing the perfusion images or using new tech-
for differentiating radiation/therapeutic necrosis from niques such as susceptibility weighted imaging, tume-
recurrent tumoral disease (Figure 3-17). Although the factive demyelinating lesions have a predilection for
two approaches have some overlap, normalizing metab- periventricular white matter and demonstrate venous
olite ratios to the contralateral normal brain tissue likely structures running through the lesion. These periven-
will increase diagnostic specificity. Figures 3-18 to 3-27 tricular veins maintain their normal architecture and are
are illustrative cases showing how this algorithm can be not disrupted or destroyed as would be expected in a
used in problem solving. glioma (Figure 3-20).
Elevation of the Cho level is consistently found in
Normalizing Cho – Cho/Cho(n) and Normalizing acute multiple sclerosis (MS) lesions. Explanations for
rCBV, Glioma and Metastases this finding have included reactive astrogliosis, demy-
The first step in this algorithm is to determine what the elination, and inflammation. Law et al. showed that the
pathologic Cho and CBV levels are relative to either mean Cho/Cr ratio in all regions of tumefactive demyelin-
contralateral or adjacent normal tissue (Figure 3-18). If ating lesions was not significantly different from that of
considerable elevation in Cho/Cho(n) or rCBV is seen, normal-appearing contralateral brain. In some patients,
then the two major pathologies to be considered are however, the Cho/Cr ratio demonstrated prominent ele-
high-grade primary glioma or metastasis. If rCBV and vation in Cho/Cr, which suggests that different degrees
Cho are highupon review of the peritumoral or perien- of inflammation or membrane proliferation in reac-
hancement region, then there is infiltrating tumor tive astrocytes may occur in different lesions. ­Typically,
98 Section I  Advanced Modalities: Protocols and Optimization

A B C

D
Figure 3-18 Patient with a primary high-grade glioma. A: Dynamic susceptibility contrast perfusion magnetic resonance imaging T2* perfu-
sion color overlay map demonstrating an increase in relative cerebral blood volume (rCBV). Cerebral blood volume relative to the contralateral
brain is markedly elevated. B: Magnetic resonance spectroscopy two-dimensional spectral map demonstrating marked elevation in choline (Cho)
compared with normalized Cho(n) in the adjacent and contralateral brain. C: rCBV color map confirming elevated rCBV. D: Elevation in Cho.
Tumoral Cho is at least twice as high as normalized Cho.

A B C
Figure 3-19 Patient with biopsy-proven primary high-grade glioma. A: Axial T1-weighted image postgadolinium showing a peripherally enhanc-
ing mass in the right frontal region with mass effect. B: Axial FLAIR weighted image demonstrating edema surrounding the enhanced component of
the lesion. C: Gradient-echo axial dynamic susceptibility contrast perfusion magnetic resonance imaging with relative cerebral blood volume color
overlay map demonstrating increase in perfusion at the rim of enhancement. However, hypovascularity in the peritumoral region suggests vasogenic
edema without infiltrating tumor. This finding suggests a metastasis as a first option, but in this case it was proven to be glioblastoma multiforme.
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 99

SECTION I
A B

C D
Figure 3-20 A 26-year-old-woman with a tumefactive demyelinating lesion A, B: Axial postcontrast T1-weighted and axial FLAIR images
showing a lesion in the left corona radiata with minimal edema and ring enhancement. C: Gradient-echo axial dynamic susceptibility contrast
perfusion magnetic resonance imaging (DSC MRI) with relative cerebral blood volume color overlay demonstrating reduced vascularity within the
lesion (arrow). However, venules within the lesion are inflamed and prominent and not destroyed or distorted, as would be seen in a high-grade
glioma. D: These venous structures are seen best on gradient-echo DSC MRI raw images at the time of contrast bolus peak. Area outlined by red
oval indicates periventricular venules.

tumefactive demyelinating lesions have relatively lower Cho/Cho(n) is lower in ischemia than glioma, so it is
Cho/Cho(n) or rCBV than gliomas or metastases (Figure critical to compare the relative concentrations of the
3-14). A more variable finding in tumefactive demyelin- abnormal Cho to the normal side. The perfusion maps
ating lesions is the presence of lactate. Local ischemia, should also demonstrate abnormal perfusion involving
neuronal mitochondrial dysfunction, and inflamma- gray and white matter (Figure 3-21). Review of the signal
tion all have been proposed as possible mechanisms for intensity curves from perfusion MRI should demonstrate
lactate and lipid elevation. Another common finding is prolongation in the mean transit time or time to peak.
reduced NAA levels, related to neuronal damage.
Therapeutic Monitoring
Acute Ischemic Stroke
If an acute ischemic stroke is considered a likely differ- Therapy-Induced Necrosis and Recurrent Tumor
ential and the findings are not conclusive on DWI, again Treatment options for brain tumors include surgi-
review Cho/Cho(n) or rCBV. Importantly, the ­normalized cal resection, chemotherapy, and radiation therapy,
100 Section I  Advanced Modalities: Protocols and Optimization

B C D
Figure 3-21 Patient with a left insular ischemia stroke that, in the subacute stage, could demonstrate contrast enhancement simulating a
glioma. A: Normalized choline (Cho)/Cho(n) demonstrating a decrease in relative Cho levels within the enhancing lesion. Cho/Cho(n) levels are
approximately 0.8, indicating that this is unlikely to be tumoral disease despite very high Cho/creatine ratio within the lesion. B: Postcontrast axial
T1-weighted and FLAIR images demonstrating some contrast enhancement and edema. Involvement of the gray and white matter suggests that this
may be ischemic. C: Dynamic susceptibility contrast perfusion magnetic resonance imaging T2* perfusion color overlay map for relative cerebral
blood volume and mean transit time (MTT) demonstrating decrease in perfusion and prolongation in MTT compatible with an ischemic stroke.

which includes gamma-knife radiosurgery, brachyther- months to several years and even decades after the
apy, and intensity-modulated radiation therapy. The end of ­therapy.
­differentiation of therapy-induced necrosis (radiation Posttherapeutic conventional MRI often depends
or chemotherapy) from recurrent or residual tumor is on enhancement patterns, edema patterns, and inter-
challenging. In the clinical setting it is best to simplify val change in dimensions to discriminate among glio-
these two entities into two diagnoses that are poten- sis, DRN, and recurrent tumor. These variables often
tially separable with DSC MRI, namely, delayed radia- are nonspecific and confusing. Six months after initia-
tion necrosis (DRN)/chemotherapy-induced necrosis tion of therapy, DSC MRI can help in determining a
versus recurrent tumor. Unfortunately, most times in good or a poor response to treatment. If substantial
clinical practice and at histopathology these two enti- elevation in rCBV occurs at any point in time, recur-
ties coexist, as it is primarily in the setting of residual rent tumoral disease is present. DSC MRI is proving
tumor that the patient receives adjuvant radiation or to be a sensitive technique in differentiating DRN,
chemotherapy. and perhaps even radiation leukoencephalopathy,
Some investigators have suggested that, particu- from recurrent tumor. Histopathologically, DRN is an
larly in the first 6 months after initiation of treat- occlusive vasculopathy that results in “stroke-like epi-
ment, a combination of residual tumor and treatment sodes.” Endothelial proliferation can be seen in the
effects or radiation leukoencephalopathy must coexist in early phase of DRN and may result in obliteration of
the same patient. By clinical definition, residual dis- the vessel lumen. Endothelial injury from radiation
ease must be within the surgical cavity for the patient leads to fibrinoid necrosis of small vessels, endothelial
to receive postoperative radiation therapy. DRN is an thickening, hyalinization, and vascular thrombosis. If
entity very distinct from radiation leukoencephalopa- radiation necrosis is a consideration, then CBV and
thy and diffuse radiation injury. DRN results in vas- cerebral blood flow typically are low because of vas-
cular and myelin damage, and it occurs from a few cular narrowing. Ktrans may be reduced because even
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 101

SECTION I
A B C

D E F
Figure 3-22 Two different patients with recurrent tumor and radiation necrosis, respectively. A: Axial postcontrast T1-weighted image
demonstrating prior left frontal craniotomy with a ring-enhancing lesion and marked edema. B: Dynamic susceptibility contrast perfusion
magnetic resonance imaging (DSC MRI) T2* perfusion color overlay demonstrating elevation in relative cerebral blood volume (rCBV)
in the enhancing component of the lesion. C: Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) T1 steady-state per-
meability curve demonstrating a very rapid initial increase in permeability compatible with a vascular phase, then a more steady leakage
typical for a highly vascular, highly permeable recurrent tumor. D: Slightly less avidly enhancing left parietooccipital lesion. E: DSC MRI
T2* perfusion color overlay demonstrating a decrease in rCBV throughout the enhancing lesion. F: DCE MRI T1 steady-state permeability
color overlay and curve demonstrating a much slower rise in signal compatible with a leaky blood–brain barrier from fibrinoid necrosis
but no vascular phase.

though enhancement is seen, the rate of enhancement Chemoradiation-Induced Pseudoprogression

typically is very slow (Figures 3-22 and 3-23). As in Data recently reported in the randomized EORTC
the algorithm shown in Figure 3-17, normalized Cho/ 22981/26981–NCIC CE.3 (European Organization for
Cho(n) will be decreased compared to the contralat- Research and Treatment of Cancer/National Cancer
eral Cho (Figure 3-24). Perfusion (rCBV) and vascular Institute of Canada) phase III trial of newly diagnosed
permeability appear to be measuring different patho- patients with GBM given temozolomide plus radio-
physiologic changes in the brain. As a result, in some therapy have provided a new standard of care. With the
instances not only are spatial differences seen in the introduction of chemoradiotherapy with temozolo-
distribution of rCBV versus permeability changes, but mide as the new standard of care for patients with GBM
one metric may be better than the other in charac- has come an increasing awareness of ­posttherapeutic
terizing radiation necrosis versus recurrent tumor ­progressive and enhancing lesions on MRI noted
(Figure 3-25). immediately after the end of treatment. These lesions
are not related to tumor progression but are a treat-
DWI in Therapeutic Follow-up ment effect. This so-called therapy-induced necrosis
Another application of DWI is in the follow-up of or pseudoprogression, which can occur in up to 20%
tumors with very high cellularity. A classic example is of patients who have been treated with temozolomide
the use of DWI in demonstrating recurrent tumor in chemoradiotherapy, can explain about half of all cases
the follow-up of medulloblastoma, which is known to of increasing lesions and enhancement after the end of
be a very cellular tumor (Figure 3-26). Despite prom- treatment. The lesions decrease in size or stabilize with-
ising results reported in the recent literature, the role out additional treatments and often remain ­clinically
of DWI in the quantification of treatment response of ­asymptomatic (Figure 3-27). The mechanisms behind
brain tumors remains investigational because of the these events have not yet been fully elucidated, but
­heterogeneous and dynamic reorganization of tumor chemoradiotherapy likely causes a higher degree of
structure leading to varying changes in tumor ADC (desired) tumor cell and endothelial cell killing. The
values. increased cell kill might lead to secondary reactions,
102 Section I  Advanced Modalities: Protocols and Optimization

A B C D

E F

G H
Figure 3-23 Patient with recurrent tumor over a 6-month period. A: Axial postcontrast T1-weighted image presurgery demonstrating a right
temporal high-grade glioma. B: Dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC MRI) T2* perfusion relative cerebral
blood volume (rCBV) color overlay demonstrating increased perfusion. C: Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI)
T1 permeability color overlay with signal intensity curve demonstrating increase in vascular permeability with marked vascular phase. D: Imme-
diate postoperative scan demonstrating surgical cavity with a small amount of residual enhancement in the medial aspect of the surgical cavity.
E: MRI 6 months from the initial surgery demonstrating recurrent tumoral disease. F: DCE MRI T1 steady-state permeability maps and curve
(G) demonstrating a very rapid initial increase in permeability compatible with a vascular phase, then a more steady leakage typical for a highly
vascular, highly permeable recurrent tumor. H: DSC MRI T2* perfusion color overlay demonstrating a decrease in rCBV throughout the enhancing
lesion compatible with a recurrent tumor.
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 103

SECTION I
A B

C D E
Figure 3-24 Patient with radiation necrosis. A: Magnetic resonance spectrum from the enhancing lesion demonstrating lower choline (Cho)
levels than the contralateral normal Cho(n) in B. Elevation in lipid and lactate is in keeping with radiation necrosis. B: Normal contralateral spec-
trum. Cho/Cho(n) is <1.0. C: Dynamic susceptibility contrast perfusion magnetic resonance imaging T2* perfusion color overlay demonstrating
decrease in relative cerebral blood volume (rCBV) in the enhancing component of the lesion. D: Localizing image demonstrating the location
of the abnormal spectrum in A and the normal spectrum in B. E: Color overlay demonstrating the location of the region of interest placed to
demonstrate low rCBV in the lesion.
104 Section I  Advanced Modalities: Protocols and Optimization

A B C

D E F G
Figure 3-25 Follow-up of glioblastoma multiforme after chemoradiotherapy in a 50-year-old patient. Mismatch between relative cerebral
blood volume (rCBV) and permeability. A: Gradient-echo T2* axial dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC
MRI) with rCBV color overlay demonstrating reduced rCBV within the lesion. B: T1 dynamic contrast-enhanced magnetic resonance imaging
(DCE MRI) showing some foci of high vascular permeability within the lesion. C: Axial T1-weighted postcontrast image showing heterogeneously
enhancing lesion in the left parietal lobe in the region of the previously resected tumor. D: Gradient-echo axial DSC MRI with rCBV color overlay
just above the previous slice again demonstrating reduced rCBV within the lesion. E–G: Spin-echo DCE MRI showing some focus of high vascular
permeability within the lesion. DCE MRI T1 steady-state permeability curve shows a very rapid initial increase in permeability compatible with
recurrent tumor. This case demonstrates a situation where permeability shows recurrent tumor in a lesion with relatively low perfusion, indicating
that perfusion and permeability correlate with different pathophysiology. In many lesions there is also often a combination of necrosis and tumor.
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 105

SECTION I
A B C

D E F
Figure 3-26 Follow-up of medulloblastoma in the posterior fossa. A–C: Diffusion-weighted images showing diffusion restriction along the
ependymal surface of the ventricular wall, with some nodularity. D: Axial T1-weighted image postcontrast demonstrating minimal contrast
enhancement. E: Apparent diffusion coefficient map confirming restriction of diffusion. F: Dynamic susceptibility contrast perfusion magnetic
resonance imaging with color overlay demonstrating increased cerebral blood volume along the ependymal surface of the ventricular wall, all in
keeping with recurrent medulloblastoma.
106 Section I  Advanced Modalities: Protocols and Optimization

Figure 3-27 Right parietooccipital glioblastoma multiforme in a 54-year-old man. Top row: Axial T1-weighted images with contrast demonstrat-
ing preoperative enhancing lesion with central necrosis. Immediately postsurgery, there appears to have a gross total resection. The patient received
radiation therapy as well as chemotherapy with temozolomide. Three months after chemoradiotherapy, increased nodular contrast enhancement
may represent pseudoprogression. Five months after therapy, the lesion demonstrates substantially decreased contrast enhancement. Middle row:
Axial FLAIR, T1-weighted image postgadolinium demonstrating increased enhancement at the surgical site. Dynamic susceptibility contrast perfu-
sion magnetic resonance imaging (DSC MRI) demonstrates decreased perfusion and dynamic contrast-enhanced magnetic resonance imaging (DCE
MRI) T1-weighted permeability color overlay map with corresponding signal intensity curve demonstrates increased permeability, which could
indicate recurrent tumor or pseudoprogression. Bottom row: Axial FLAIR, T1-weighted image postgadolinium demonstrating decreased edema,
mass effect, and enhancement at the surgical site. DSC MRI demonstrates decreased perfusion and DCE MRI T1-weighted permeability color over-
lay map with corresponding signal intensity curve demonstrates decreased permeability, which could indicate pseudoprogression. (Reproduced
from Law M, Lacerda S. Magnetic resonance perfusion and permeability imaging in brain tumors. Neuroimaging Clin N Am 2009;19(4):527-557.)

such as edema and ­abnormal vessel permeability in the space and consequent brain edema. Furthermore, if cap-
tumor area, that mimic tumor progression, in addition illary permeability is altered, damage from chemother-
to subsequent early treatment-related necrosis in some apy may occur earlier and be more severe. Radiotherapy
patients and milder subacute radiotherapy reactions in may enhance the efficacy of chemotherapy by maximiz-
others. Advanced neuroimaging findings in pseudopro- ing drug uptake at the cell membrane, disrupting the
gression suggest a decrease in CBV values and a slight blood–brain barrier, and/or altering cell metabolism.
decrease in vascular permeability (as well as an increase This can lead to the observation of early radiologic
in Cho levels), which are in keeping with the proposed increase in contrast enhancement on MRI consequent
pathophysiology previously described. These findings to alterations in the blood–brain barrier, thus falsely
(along with the contrast enhancement) usually regress suggesting tumor progression. This phenomenon may
6 to 9 months after the initial commencement of temo- be the expression of treatment-induced necrosis leading
zolomide and radiation therapy and possibly other to disruption of the blood–brain barrier and passage
chemoradiation regimens. Further research is needed to of contrast material. The potential impact of O6-meth-
establish reliable imaging parameters that distinguish ylguanine–DNA methyltransferase (MGMT) promoter
between true tumor ­progression and pseudoprogression methylation status has been described in this group of
or treatment-related necrosis. patients. A retrospective analysis of newly diagnosed
Radiation injury to the CNS may, in fact, depend on GBM patients with assessable MGMT methylation status
increased capillary permeability induced by radiother- found that MGMT promoter methylation status can pre-
apy, leading to fluid transudation into the interstitial dict the incidence and outcome of pseudoprogression.
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 107

SECTION I
A B

C D
Figure 3-28 A 52-year-old man with a history of colon cancer, who presented with altered conscious state. A, B: Axial FLAIR and T2-weighted
images demonstrating a bacterial abscess in the left thalamus. C: Postcontrast axial T1-weighted image demonstrating ring enhancement with a
likely “daughter” component in the left ventricle. D: Axial diffusion-weighted images demonstrating diffusion restriction and hyperintensity in
keeping with a pus-filled cavity rather than tumor necrosis.
Continued

CNS INFECTIONS: BACTERIAL the enhancing capsule and the region of surrounding
AND TUBERCULOUS INFECTIONS edema. Typically bacterial abscesses demonstrate some
restriction of diffusion on DWI (Figure 3-28). Bacterial
A major differential diagnosis for ring-enhancing lesions abscesses also have demonstrated the by-products of
are intracranial abscesses, which may be bacterial, tuber- bacterial metabolism, amino acid levels of 0.9 ppm with
culous, or parasitic. The diagnosis of a brain abscess or without the presence of succinate, acetate, alanine,
usually is made by reviewing the clinical, hematologic, and glycine (Figure 3-29). Although ring-enhancing
and conventional imaging findings. In some instances lesions with diffusion restriction are believed to likely
where the diagnosis is not straightforward, combin- represent bacterial abscesses, other pathologies, such as
ing MRSI and DSC MRI may increase the specificity of gliomas, metastases, and lymphomas, can demonstrate
neurodiagnosis. There is decreased perfusion within diffusion restriction (Figures 3-30 and 3-31). This is a
the central portion of an abscess and in the regions of well-recognized pitfall.
surrounding edema compared with a ­neoplasm. There Typically tuberculous granulomas do not show dif-
may be a very thin rim of increased perfusion between fusion restriction, as well as toxoplasmosis, whereas
108 Section I  Advanced Modalities: Protocols and Optimization

E F

G
Figure 3-28—cont’d E, F: Gradient-echo axial dynamic susceptibility contrast perfusion magnetic resonance imaging with relative cerebral
blood volume (rCBV) color overlay demonstrating multiple regions of interest within the capsule of the lesion show a thin rim of increased rCBV
on the lateral cortical side of the lesion. G: rCBV signal intensity curve again confirms some increased perfusion in the capsule of the lesion. Haris
et al. have demonstrated that the inflammatory cells in the wall of the abscess are positive for vascular endothelial growth factor expression.
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 109

SECTION I
A B C

D E F
Figure 3-29 A 61-year-old man with a bacterial abscess. A: Postcontrast axial T1-weighted image demonstrating a ring-enhancing lesion in the
right parietooccipital regions. B, C: Axial FLAIR and T2-weighted images demonstrating a moderate degree of vasogenic edema seen in bacterial
abscesses. D, E: Diffusion-weighted imaging with apparent diffusion coefficient map demonstrating diffusion restriction with hyperintensity in
keeping with bacterial pus. F: Magnetic resonance spectroscopy showing the presence of succinate (S) at 2.4 ppm; acetate (A) at 1.92 ppm; lipid/
lactate (Lip/L) at 1.3 ppm; and leucine, isoleucine, and valine (AA) at 0.9 ppm. Glycine (Gly) at 3.56 ppm and alanine (Al) at 1.5 ppm can some-
times also be seen but are not clearly seen in this patient.
110 Section I  Advanced Modalities: Protocols and Optimization

A B C

D E F G
Figure 3-30 A 50-year-old patient with a history of lung cancer and biopsy-proven metastasis to the central nervous system (CNS). A, B: Axial
T2- and postcontrast T1-weighted images demonstrating a mass with central necrosis and ring enhancement located in the occipital lobe.
C: Diffusion-weighted image demonstrating diffusion restriction in the center of the lesion. D: A 68-year-old patient with a history of breast cancer
and biopsy-proven metastasis to the CNS. D: Axial FLAIR image showing at least three lesions: one in the white matter of the right frontal lobe,
one in the splenium of the corpus callosum, and one in the posterior aspect of the left insula. E: Axial T1-weighted image showing peripherally
enhancing lesions (red arrows). F: Diffusion-weighted image demonstrating restricted diffusion within these lesions (red arrows). G: Gradient-echo
axial image demonstrating no blood products within the lesions. These two cases illustrate that some metastases can, at least in the early stages,
show some diffusion restriction and in this regard must be recognized as a pitfall not to be confused with a bacterial abscess. (Courtesy Dr. Nelson
Fortes, Med Imagem, Brazil.)
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 111

SECTION I
A B C

D E F
Figure 3-31 A 62-year-old man with biopsy-proven glioblastoma multiforme (GBM). A–C: Axial T2-weighted and axial FLAIR images showing
a mass in the left occipital region. D: Axial postcontrast T1-weighted image showing a mass with central necrosis and predominantly peripheral
enhancement. E: Diffusion-weighted image demonstrating high signal in the central portion of the lesion. F: Gradient-echo axial image dem-
onstrating some blood products within the lesion, which may explain the high signal intensity observed in diffusion-weighted imaging. This is
another pitfall in that GBMs can present with blood products centrally, which can be misinterpreted as a bacterial abscess.
112 Section I  Advanced Modalities: Protocols and Optimization

A B

C D
Figure 3-32 A 26-year-old woman with toxoplasmosis (perfusion, diffusion, and spectroscopic findings often similar to those seen in tuber-
culous abscesses). A, B: Axial T1-weighted images demonstrating a dominant mass in the right frontal region with a moderate degree of edema.
There are multiple other enhancing lesions close to the corticomedullary junction sometimes seen in toxoplasmosis. C: Axial T2-weighted image
demonstrating edema as well as mass effect on the left frontal horn. D: Diffusion-weighted image demonstrating low signal in the abscess cavity
indicating free diffusion.
Continued

tuberculous abscesses can present with diffusion restric- c­ orrelated with microvascular density and the expres-
tion. However, different from bacterial abscesses, tuber- sion of VEGF in excised tuberculomas. There was also
culous abscesses demonstrate only lactate and lipid a significant decrease in rCBV in response to antituber-
peaks (Figure 3-32) without the presence of glycine, culous therapy.
succinate, acetate, and alanine. In vivo studies have
demonstrated these metabolites (including lipids) at OTHER INFLAMMATORY MIMICS/
0.9, 1.3, 2.0, and 2.8 ppm and phosphoserine at 3.7
ENCEPHALITIS/ENCEPHALOPATHY
ppm. Haris et al. also recently demonstrated that physi-
ologic perfusion indices such as rCBV, cerebral blood Inflammatory lesions of the CNS, such as cerebritis,
flow, and Ktrans appear to be useful in differentiating encephalitis, and encephalopathy, can mimic tumor.
infective from neoplastic brain lesions. Their study of Typically brain inflammation is associated with an
103 patients demonstrated that infective lesions showed element of vasculitis. A full discussion of all of the
the highest permeability, followed by high-grade glio- etiologies of vasculitis is beyond the scope of this
mas and low-grade gliomas. CBV ­measurements also chapter. Noninfectious vasculitides are characterized
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 113

SECTION I
E F

H
G
Figure 3-32—cont’d E, F: Gradient-echo axial perfusion MRI with relative cerebral blood volume (rCBV) color overlay maps demonstrating
some decrease in rCBV. G, H: Axial FLAIR localizing image showing the location of a voxel placed for magnetic resonance spectroscopy, which
demonstrates elevation in lipid and lactate. The finding of the combination of lipid, lactate, decreased rCBV, and diffusion is consistent with either
toxoplasmosis or a tuberculous abscess.

by ­inflammatory cell infiltrates, with varying degrees of of substantial blood–brain barrier breakdown, which
multinucleated giant cells, granuloma formation, and may artifactually cause an elevation in rCBV. CBV cor-
fibrinoid necrosis. Several of these vasculitides result in rection should demonstrate a more accurate estima-
vessel wall fibrosis if the disease state becomes chronic. tion of true CBV.
There is variation within the vasculitides in terms of
the part of the vessel wall (intima, media, adventitia) PITFALL CASES WITH ADVANCED
and the type of vessel (large-vessel, medium-vessel, IMAGING
small-vessel, or vein) involved. Systemic vasculitides
can cause neurologic symptoms either primarily by Low-Grade Oligodendrogliomas
affecting cranial vessels or secondarily by causing vas- Usually Have Elevated Perfusion
cular occlusion or embolism. Consequently, inflamma-
tory lesions of the brain usually result in reduced rCBV Numerous investigators have characterized DSC
because of perivascular infiltrate causing some vascular MRI findings in oligodendroglial tumors. Oligoden-
narrowing ­(Figures 3-33). The caveat is the occurrence drogliomas are slowly growing, typically low-grade
114 Section I  Advanced Modalities: Protocols and Optimization

A B C D

E F G H
Figure 3-33 A 46-year-old-man with human immunodeficiency virus and progressive multifocal leukoencephalopathy (PML) (perfusion,
diffusion, and spectroscopic findings often similar to those seen in encephalitis). A, B: Axial FLAIR and T2-weighted images demonstrating
abnormal increase in signal in the left parietooccipital white matter. C: Axial FLAIR image demonstrating the position of the voxel for magnetic
resonance spectroscopy. D: Magnetic resonance spectroscopy demonstrating decrease in N-acetylaspartate as well as increased lipid and lactate.
The normalized Cho/Cho(n) should be low. E: Gradient-echo axial perfusion MRI with relative cerebral blood volume (rCBV) color overlay map
demonstrating decrease in rCBV. F, G: Axial diffusion tensor imaging (DTI) color overlay fractional anisotropy (FA) and directional color image
demonstrating decrease in white matter integrity. H: Fiber tractography generated from DTI confirms loss of white matter integrity in the left
parietooccipital white matter.

tumors. Oligodendrogliomas have been shown to noninvasive physiologic imaging markers of poten-
demonstrate high CBV even in lower-grade tumors. tial molecular signatures that identify microvascular
The histologic appearance of oligodendrogliomas ­proliferation, ­malignant transformation, patient out-
consist of a dense network of branching capillaries come, and response to therapy.
that produce a vascular pattern resembling chicken
wire in addition to the “fried-egg” appearance of the Extraaxial Neoplasms
tumor cells, which in part accounts for the increase (Meningioma, Schwannoma) Also
in rCBV.
Have High Perfusion
Recently, there has been promise in the treat-
ment of oligodendrogliomas with the discovery of Relative CBV may not be as reliable in differentiating
the ­association between 1p 19q chromosomal arm extraaxial from intraaxial lesions in the brain because
deletions and improved responsiveness to chemo- substantial contrast leakage from the lack of a blood–
therapy. Given the histopathologic and molecular evi- brain barrier in extraaxial lesions can give erroneously
dence supporting increased neovascularity in gliomas low or high uncorrected CBV values. However, evalu-
with ­oligodendroglial components, the association ating the signal intensity–time curve and determining
between 1p 19q deletions and increased perfusion the degree of permeability may be helpful in the clini-
seems to warrant further investigation. Investigators cal setting. In extraaxial lesions, the signal intensity–
found that elevated rCBV raises the possibility of a 1p time curve demonstrates immediate and continued
19q chromosomal deletion in human gliomas. Thus, leakage of contrast compared with intraaxial lesions.
rCBV may serve as an important physiologic imaging Meningiomas are the most common extraaxial tumors
biomarker for identifying gliomas with 1p 19q chro- and ­usually are a straightforward diagnosis on conven-
mosomal deletions conferring higher chemosensitiv- tional MRI, obviating the need for DSC MRI or biopsy.
ity (Figure 3-34). Furthermore, DSC MRI may provide rCBV and Ktrans usually are elevated in meningiomas.
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 115

SECTION I
A B

C D
Figure 3-34 A 63-year-old man with pathology-proven oligodendroglioma and high perfusion relative cerebral blood volume (rCBV) of 6 and
1p19q allelic deletions. A: Axial FLAIR image demonstrating a cortically based right frontal lesion with mass effect. B: Contrast-enhanced axial
T1-weighted image demonstrating a minimally enhancing mass in the right frontotemporal region. C: Axial dynamic susceptibility contrast perfu-
sion magnetic resonance imaging with rCBV color overlay map showing a lesion with very high perfusion and rCBV of 6. Low-grade oligodendro-
gliomas have been described to have elevated perfusion. This is a pitfall when using perfusion to determine tumor grade. D: Fluorodeoxyglucose
positron emission tomographic (FDG PET) image demonstrating increased FDG uptake in the lesion.
Continued
116 Section I  Advanced Modalities: Protocols and Optimization

E F

G
Figure 3-34—cont’d E: Color-coded directional fractional anisotropy map demonstrating the circumscribed oligodendroglioma likely is
displacing rather than destroying the adjacent corticospinal tracts in the posterior (blue) and anterior (green) limbs of the internal capsule.
F, G: Fiber tractography confirms the integrity of the corticospinal tracts.

­ eningiomas are known pathologically and at angiog-

M be a challenge. Lower vascular permeability has been
raphy to be vascular tumors. There also appears to be found in typical meningiomas compared to acoustic
good correlation between Ktrans and the histologic grade neuromas.
of meningiomas (Figure 3-35). Pathologically, higher
Ktrans measurements may be related to the degree of Advanced MRI as Biomarkers for
micronecrosis found in atypical meningiomas. Because Therapeutic Response in Novel
the atypical and typical variants of meningioma have
Antiangiogenic Agents
different recurrence rates, measurement of Ktrans pro-
vides a prospective measure of tumor behavior, and this Malignant gliomas, particularly recurrent anaplas-
­information could help avoid surprises, such as brain tic gliomas and GBM, are highly refractory to therapy.
invasion, that could be planned for successfully if the A key feature of malignant gliomas, such as GBM, is their
information were available to the neurosurgeon preop- tendency to infiltrate surrounding tissues. This invasive
eratively. property often precludes total surgical resection and
DSC MRI can increase the sensitivity of diagnosis in makes it difficult to treat with radiation without damag-
extraaxial masses. Differentiating between meningioma ing normal brain parenchyma. Because of the difficulty
and acoustic neuroma at the cerebellopontine angle can in obtaining total resection, patients with GBM have a
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 117

SECTION I
A B

C D
Figure 3-35 Pathologically confirmed atypical meningioma (World Health Organization grade II). A, B: Axial T2- and T1-weighted postgado-
linium images. C, D: Coronal T2- and T1-weighted images demonstrating a falcine meningioma with moderate edema.
Continued

median survival of less than 1 year, despite aggressive Bevacizumab (Avastin) is a humanized murine mono-
treatment. Of the approximately 35,000 Americans clonal antibody against the VEGF receptor. Published
diagnosed with primary brain cancer each year, almost data on the role of Avastin in primary brain tumors are
half with high-grade (World Health Organization class much more limited. One study demonstrated a 50%
III– IV) gliomas will die of their disease within 2 years conventional MRI response rate in 14 patients with
if treated and in less than 6 months if untreated. These recurrent high-grade gliomas. Of these patients, four
gliomas are highly vascular and likely are the result of died (mean survival after treatment: 116 days). Two had
tumoral up-regulation of angiogenic growth factors, what the authors described as “mixed progressive dis-
such as VEGF. Angiogenesis appears to play a major role ease,” and the other two had “partial response,” suggest-
in the recurrent and refractory nature of these ­high-grade ing that radiographic improvement does not correlate
tumors. As a result, pharmaceutical companies have well with clinical outcome.
invested heavily into researching and developing effec- Initial studies with antiangiogenic agents such as
tive antiangiogenesis agents. One of the few agents cur- thalidomide demonstrated that perfusion imaging was
rently approved by the United States Food and Drug able to more accurately predict overall survival and pro-
Administration (FDA) is bevacizumab (Avastin). gressive disease than conventional MRI. More recently,
118 Section I  Advanced Modalities: Protocols and Optimization

E F

G
Figure 3-35—cont’d E: T1 localizing image with gradient-echo axial dynamic susceptibility contrast perfusion magnetic resonance imaging
(DSC MRI) and relative cerebral blood volume color overlay demonstrating high rCBV throughout the lesion. F: Gradient-echo axial DSC MRI
signal intensity curve depicting signal intensity drop with the curve not returning to the preinjection baseline, indicating increased leakage/vas-
cular permeability. G: T2* signal intensity curve demonstrating increased vascular permeability in atypical meningiomas compared with typical
meningiomas.

we have used CBV and permeability measurements to likely that, in the future, a combination of drugs will tar-
follow patients taking Avastin. To date, it appears that get different components of glioma biology that will be
radiographically on conventional MRI, CBV, and per- most effective. Regardless of therapy, it will be evident
meability measurements, most patients demonstrate that quantitative MR measures of perfusion, diffusion,
a response to treatment with a decrease in enhanc- and other pathophysiologic parameters will become
ing volume, CBV, and vascular permeability. However, early surrogate biomarkers of therapeutic response.
many of these patients do not demonstrate significant
improvement in time to progression or overall survival PROBLEM SOLVING IN
(Figures 3-36 and 3-37). Pathologically, treatment with
NEURODEGENERATIVE DISEASES
antiangiogenic agents may alter glioma biology such
that the tumor becomes more invasive and cellular in Neurodegenerative diseases include the dementias,
response to the deprivation of angiogenesis. DWI and/or which comprise various pathologic entities such as
­diffusion tensor imaging are beginning to demonstrate primary demyelinating disease, Parkinson disease,
the increased cellularity in some of the treated gliomas. amyotrophic lateral sclerosis, Alzheimer disease, fronto-
As with many other disease processes such as human temporal dementia, corticobasal degeneration, progres-
immunodeficiency virus and tuberculous infection, it is sive supranuclear palsy, and dementia with Lewy bodies.
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 119

SECTION I
A B C

D E F
Figure 3-36 Pathologically proven recurrent glioblastoma multiforme (World Health Organization grade IV). A: Axial T1-weighted postgado-
linium image. B: Gradient-echo axial dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC MRI) with relative cerebral
blood volume (rCBV) color overlay demonstrating high rCBV within the lesion. C: rCBV values within the lesion demonstrating high rCBV values.
D: Follow-up T1-weighted image demonstrating a good response to therapy. E: Gradient-echo axial DSC MRI with rCBV color overlay demonstrat-
ing reduced rCBV within the lesion. F: rCBV values following treatment demonstrate marked decrease in rCBV values.

Advanced imaging techniques have been used to help Frontotemporal dementia is a clinical syndrome
in problem solving some of these neurodegenerative associated with volume loss of the frontal and anterior
­disorders. temporal lobes of the brain. Originally known as Pick
The clinical diagnosis of these dementia subtypes is disease, the name and classification of frontotempo-
based on proposed consensus clinical criteria for each ral dementia has been a topic of discussion for more
disease. However, distinguishing among the dementia than a century. Although pharmacologic treatment
subtypes by clinical examination alone, particularly of dementia patients has not been satisfactory, recent
during the early stages, continues to be difficult. The meta-analyses have shown that early treatment with
diagnosis of Alzheimer disease has benefited from cholinesterase inhibitors could be beneficial for patients
the utility of fluorodeoxyglucose positron emission with Alzheimer disease. Thus, early discrimination of
tomographic imaging. MRS has also demonstrated patients with Alzheimer disease from those with fron-
its utility in demonstrating elevation in myoinositol totemporal dementia/Pick complex has become more
and decrease in glutamine/glutamate complexes dur- important than the precise differentiation of dementia
ing the early stages of the disease. Usually a decrease subtypes. Patients with frontotemporal dementia/Pick
in NAA also is seen. These metabolite changes are complex have been shown to demonstrate a frontal pre-
believed to occur globally. In addition, early during dominant decrease in NAA/Cr ratios, whereas patients
the course of the disease, particularly in patients with with Alzheimer disease showed a posterior dominant
mild cognitive impairment, metabolite changes are decrease. These different distributions of metabolic
seen in the posterior cingulate gyrus and temporal changes may represent the underlying pathologic pro-
lobes (Figure 3-38). cesses in each disease (Figure 3-39).
120 Section I  Advanced Modalities: Protocols and Optimization

A B C

D E F
Figure 3-37 Pathologically proven recurrent glioblastoma multiforme after 2 months of therapy with Avastin. Same patient as shown in Figure
3-36. A, B: Axial diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) map demonstrating diffusion restriction within
the lesion. C: Region of interest demonstrating diffusion values. D: DWI and ADC image demonstrating a marked decrease in signal suggesting
possible increase in tumor cellularity, decrease in edema, and possible increase in invasiveness within the recurrent glioma. This may be a biologic
response to removal of the angiogenic component as well as decrease in edema from lower vascular permeability.
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 121

SECTION I
A B C
Figure 3-38 Patient who initially presented with mild cognitive impairment progressing to Alzheimer disease (AD). A: Initial magnetic reso-
nance scan (MRS) in 1997 demonstrating minimal volume loss and location of the MRS voxel within the posterior cingulate gyrus. MRS shows
mild elevation in myoinositol (MI), decrease in glutamine/glutamate (Glx), and decrease in N-acetylaspartate (NAA). B: Follow-up scan in 1999
demonstrating similar findings to those seen in 1997. C: MRI and MRS in 2001 in the same patient demonstrating increasing volume loss, par-
ticularly involving the temporal lobes. MRS demonstrates progressively increasing MI and decreasing NAA in AD. (Courtesy Dr. Nelson Fortes,
Med Imagem, Brazil.)
122 Section I  Advanced Modalities: Protocols and Optimization

A B

C D E F
Figure 3-39 Patient who presented with frontotemporal dementia (FTD). A, B: Sagittal T1- and axial T2-weighted images demonstrating
some volume loss in the frontotemporal regions. Typically with marked volume loss, the sulci are described as having a “knife-like” appearance.
C, D: Magnetic resonance spectroscopy(MRS) in the posterior gray and white matter demonstrating fairly normal metabolite concentrations. E, F:
MRS in the frontal regions demonstrating a marked decrease in N-acetylaspartate (NAA) in FTD. The predilection from the frontal regions helps
to differentiate it from Alzheimer disease, which has a more posterior predilection (see Figure 3-38). (Courtesy Dr. Nelson Fortes, Med Imagem,
Brazil.)
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 123

SECTION I
A

B C D
Figure 3-40 Patient with amyotrophic lateral sclerosis (ALS). A: Axial FLAIR image demonstrating increase in signal along the corticospinal tracts
(CST) extending from the precentral sulcus through the posterior limb of the internal capsule down into the brainstem. B: Axial directional color-
coded fractional anisotropy (FA) maps in a normal patient demonstrating the superior to inferior direction of the CST (white arrows). C, D: Patient
with ALS demonstrating decrease in FA along the CST (white arrows in C) seen on both the directional and magnitude color-coded maps.

Amyotrophic lateral sclerosis (ALS), or motor neuron PROBLEM SOLVING IN WHITE

disease, is a neurodegenerative disorder of unknown MATTER, METABOLIC DISEASES,
origin. It occurs in sporadic (90%–95% of cases) and AND DEVELOPMENTAL DISEASES
familial (5%–10%) forms. It is characterized pathologi-
cally by selective degeneration of somatic motor neu- For a more complete review of how to problem solve with
rons of the brainstem and spinal cord (lower motor MRS in metabolic and pediatric white matter disease, see
neurons) and of large pyramidal neurons of the motor the review by Cecil and Kos entitled “Magnetic resonance
cortex (upper motor neurons), with eventual loss of spectroscopy and metabolic imaging in white matter
fibers in the corticospinal tracts. MRI studies using diseases and pediatric disorders.” Numerous metabolite
T2-weighted and fluid-attenuated inversion recovery disease have a metabolic signature on MRS, and a dis-
(FLAIR) or fast spin-echo (FSE) sequences have shown cussion of this topic is beyond the scope of this text. An
that qualitatively increased signal intensity in the cor- example of how MRS can be useful in problem solving
ticospinal tracts (Figure 3-40), decreased signal inten- is Canavan disease, which has a fairly specific metabolite
sity in the precentral gyrus gray matter (motor cortex), finding. Canavan disease is an inherited disorder (auto-
or both occur in some patients with ALS. Metabolic somal recessive) caused by a deficiency in aspartoacylase,
changes also have been demonstrated in the subset which results in progressive white matter vacuolization.
of ALS patients with precentral gyrus signal changes This disorder has been localized to chromosome 17p.
on imaging, and significantly increased Ins was asso- Patients present with early psychomotor retardation,
ciated with cortical hypointensity on FSE images have megalencephaly, blindness, and spasticity. Aspartoacylase
been shown in the precentral sulcus. Diffusion tensor aids in the metabolism of NAA into acetate and aspartate,
­imaging demonstrates a decrease in fractional anisot- and NAA buildup ensues in patients with aspartoacylase
ropy within the corticospinal tracts seen on color-coded deficiency. Prominent NAA peaks have been reported in
fractional anisotropy maps (Figure 3-40). These find- all published cases of MRS and Canavan disease (Figure
ings can be important for differentiating ALS from 3-41). Decreased choline has been noted, as has lactate
other neurodegenerative diseases. elevation and Cr decrease in a few cases.
124 Section I  Advanced Modalities: Protocols and Optimization

B C
Figure 3-41 Patient with Canavan disease. A: Axial T2-weighted images demonstrating diffuse increase in signal intensity throughout the visu-
alized white matter. There is also increased signal within the globus pallidus and anterior thalami bilateral, sometimes seen in Canavan disease.
B: Localizing T2-weighted image showing the location of the voxel for magnetic resonance spectroscopy (MRS). C: MRS showing the very char-
acteristic elevation in N-acetylaspartate (red arrow). There is also a pronounced decrease in creatine. (Courtesy Dr. Ronnie Peterson, Santa Casa,
Porto Alegre, Brazil.)
 Chapter 3 Advanced MR (MR Spectroscopy, Diffusion Imaging, and Perfusion Imaging) 125

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 chapter 4

PET/CT Imaging in Squamous Cell

Carcinoma of the Head and Neck
Lale Kostakoglu

INTRODUCTION
have distinct biologic behavior such that regional lymph
Squamous cell carcinoma (SCC) of the head and neck node and distant metastases occur more frequently in
(HNSCC) constitutes more than 90% of head and neck oropharyngeal SCCs due to a rich lymphatic network
cancers, and salivary gland tumors, lymphoma, melanoma, that is not as abundantly present in the oral cavity.
and sarcoma account for the remaining 10%. The majority The borders for oral cavity consist of the lips, floor
of HNSCC patients present with locally advanced disease; of the mouth, gingivobuccal mucosa, hard palate, oral
less than 50% of newly diagnosed patients have early-stage tongue (anterior two thirds of tongue), floor of mouth,
disease. Management depends primarily on a combina- and retromolar trigone. The most common tumors of
tion of T and N staging. The TNM (tumor node metasta- the oral cavity involve the oral tongue and the floor of
sis) system is used for staging HNSCC, with the T stages the mouth. The oropharynx contains the base of the
being specific to each anatomic subdivision but the N and tongue (posterior third of the tongue) and the tonsils
M staging being shared (Table 4-1). Usually, the presence and extends from the palate to the epiglottic valleculae,
of subclinical nodal and distant metastases determines including the posterior and lateral pharyngeal walls. The
whether the patient can be treated with function-sparing most common cancers in this location arise from the
therapy. ­Contrast-enhanced computed tomography (ceCT) tonsils and base of the tongue.
or magnetic resonance imaging (MRI) has been the pri- Patients who present with early-stage SCCs often
mary imaging modality for evaluating HNSCC at both can be successfully treated with either surgery or
staging and restaging. Nonetheless, this approach has been radiotherapy alone. The treatment strategy for more
shifting toward the use of positron emission tomography advanced disease depends on the involved subsite and
integrated with computed tomography using fluorodeoxy- may involve chemoradiation followed by resection and/
glucose (FDG PET/CT) in the past several years. Although or neck dissection if necessary, followed by adjuvant
rare at initial presentation, the presence of distant metas- ­chemoradiation.
tasis as well as second primary cancers of the upper
aerodigestive tract should be evaluated by whole body Does FDG PET/CT Have a Primary
imaging, preferably by FDG PET/CT as a metabolic imag- Role in Evaluation of Primary
ing modality. If concern exists regarding the invasion of Tumor in Oral Cavity and
muscle, nerves, or bone, an MRI study may be appropriate Oropharyngeal Cancers?
for better evaluation of the extent of tumor involvement.
This chapter reviews FDG PET/CT imaging in oral cavity, Accurate determination of the T stage requires knowledge
oropharyngeal, and laryngeal SCCs, which constitute the of the size of the primary tumor, depth of invasion, and
majority of HNSCC. Other malignancies of the head and infiltration of adjacent structures. ceCT or MRI has been
neck do not fall in the scope of this review. In addition, widely used when assessing the T stage at initial presenta-
this chapter reviews the subsites of HNSCC with respect tion. MRI is the preferred modality for evaluation of peri-
to regional anatomy and nonmalignant causes of FDG neural spread or invasion of the bone. FDG PET/CT is
uptake, because proper interpretation of PET/CT images highly sensitive for detection of primary HNSCCs; how-
requires a thorough understanding of these subjects. ever, it has not been proven to be superior to standard
anatomic imaging modalities in T staging. Understand-
ORAL AND OROPHARYNGEAL ably, the metabolic information alone is not sufficient to
CANCERS provide T-stage information without the association of
a high-resolution ceCT study or MRI. The best approach
What Are the Anatomic Subsites is the combination of both FDG PET and ceCT data into
to Evaluate in Oral Cavity and one study, particularly when the objective is to improve
diagnostic specificity (Figures 4-1 through 4-3). The
Oropharyngeal Cancers?
other goal is accurate determination of bone invasion to
Oral cancers are anatomically divided into the oral cav- avoid unnecessary morbid results with surgical interven-
ity and oropharynx, which in turn are divided into sev- tion (see Is FDG PET Useful in Evaluation of Bone Inva-
eral anatomic subsites. The SCCs of these two regions sion for further discussion with case examples).

126
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 127

Table 4-1 N
 and M Staging for Squamous Cell
What Are the Oral Cavity Cancer

SECTION I
­Carcinomas of the Head and Neck
Subtypes?
N STAGING
SCC of Oral Tongue
NX Regional lymph nodes cannot be assessed The majority of oral tongue SCC involves the lateral bor-
N0 There is no regional nodes metastasis der or ventral surface of the tongue (Figure 4-4, A). The
tongue contains intrinsic and extrinsic musculature in
N1 Metastasis in a single ipsilateral lymph node, <3 cm* which the genioglossus muscle forms the main bulk of
N2 Metastasis in a single ipsilateral lymph node, > 3 cm and the extrinsic tongue. Owing to the anatomic characteris-
≤ 6 cm; or metastasis in multiple ipsilateral lymph nodes, tic of the genioglossus muscle, tumors can easily extend
none > 6 cm; or metastasis in bilateral or contralateral toward the anterior floor of the mouth (Figures 4-4, B,
lymph nodes, none >6 cm
and 4-5, A and B). The prognosis mainly depends on the
N2a Metastasis in a single ipsilateral lymph node, > 3cm depth of invasion. Involvement of the extrinsic muscles of
but < 6 cm the tongue and extension into the floor of mouth are rel-
N2b Metastasis in multiple ipsilateral lymph nodes, atively easy to detect on PET/CT imaging (Figure 4-5, B).
none > 6 cm Extensive local tumor spread may involve the soft palate
N2c Metastasis in bilateral or contralateral lymph nodes, via the palatoglossus muscle and from the soft palate
none > 6 cm to the nasopharynx (Figures 4-5, A and C). The man-
N3 Metastasis in a lymph node > 6 cm
agement changes if the tumor crosses the midline of
the tongue and/or extends, posteriorly into the base
M STAGING of tongue (Figure 4-5, B). Treatment of the tongue and
MX distant metastasis cannot be evaluated floor of the mouth SCC is performed based on a com-
promise between therapeutic necessity and functional
M0 no distant metastasis
and esthetic preservation. Surgery and postoperative
M1 distant metastasis radiation are mainstays of therapy. Most tongue SCCs
*All measurements are in greatest dimension
involving the tongue base are confined to one side of
“U” and “L” are designations that may be given in addition to indicate the level the tongue, allowing for a partial glossectomy. However,
of metastasis above the lower border of the cricoid cartilage (U) or below the medial extension crossing the midline necessitates a
lower border of the cricoid cartilage (L).
Adapted from the American Joint Committee on Cancer (AJCC), Chicago, total glossectomy in surgically resectable cases (Figure
Illinois. The original source for this material is the AJCC Cancer Staging 4-4). In large excisions, a myocutaneous flap is used
Manual, Seventh Edition (2010) published by Springer-Verlag New York, to cover the defect. Mandibular extension of tongue
www.cancerstaging.net.
base carcinoma can dramatically change the operative

Figure 4-1 A 49-year-old man recently diagnosed with tonsillar squamous cell carcinoma (SCC), referred for staging with FDG PET/CT per-
formed with contrast-enhanced high-resolution CT. PET/CT axial images demonstrate increased FDG uptake (SUVmax 12.0) in the left tonsillar
fossa corresponding to a soft tissue fullness with ill-defined margins, with enhancement equal to that of muscles and measuring approximately
2.0 cm (T1), consistent with tonsillar SCC (arrow). Additionally, an enlarged level IIB lymph node measuring 2.3 cm (N1) shows heterogeneous
attenuation with increased FDG uptake (SUVmax 6.6), consistent with ipsilateral lymph node metastasis (arrowhead). AJCC staging: T1N1MX, stage
III disease.
128 Section I Advanced Modalities: Protocols and Optimization

Figure 4-2 A 62-year-old patient recently diagnosed with floor of the mouth squamous cell carcinoma, referred for staging with FDG PET/CT
performed with contrast-enhanced high-resolution CT. FDG PET/CT axial images reveal increased FDG uptake (SUVmax 8.5) in the left floor of the
mouth, anteriorly, corresponding to an enhancing mass abutting the mandible and measuring 2.8 cm (T2), consistent with the patient’s primary
malignancy (arrows). There is no evidence of bone invasion (bone windows not shown) or lymph node metastasis (N0). AJCC staging: T2N0MX,
stage II disease.

Figure 4-3 A 50-year-old man recently diagnosed with base of tongue squamous cell carcinoma, referred for staging with FDG PET/CT per-
formed with contrast-enhanced high-resolution CT. FDG PET/CT axial images reveal increased FDG uptake (SUVmax 13.5) corresponding to a
bulging mass situated in the right base of tongue extending caudally to the oropharynx, with narrowing of the pharyngeal lumen and measuring
4.1 cm (T3), consistent with the patient’s known oropharyngeal malignancy. A nonenhancing enlarged right level II lymph node with increased
FDG uptake (SUVmax 10) is consistent with ipsilateral regional metastatic disease (N1). AJCC staging: T3N1MX, stage III disease.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 129

SECTION I
A

B
Figure 4-4 A 42–year-old man recently diagnosed with tongue cancer, referred for staging with FDG PET/CT performed with noncontrast-
enhanced low-dose CT. A: FDG PET/CT axial images reveal an irregular area of increased FDG uptake (SUVmax 8.4) in the ventral surface of the
mobile tongue, measuring between 2 and 4 cm (T2), mainly on the right but crossing the midline (arrow). B: The tongue mass extends into the
base of tongue and spreads caudally into the floor of mouth involving the right-sided genioglossus muscle (arrowhead) and probably hyoglossus
muscle (small arrow). Squamous cell carcinoma of the tongue often involves genioglossus muscle. There is no evidence of lymph node metastasis.
AJCC staging: T2N0MX, stage II disease.

approach for therapy (see Is FDG PET Useful in Evalua- (Figure 4-6, B). Because the genioglossus muscle is an
tion of Bone Invasion for further discussion). essential part of both the floor of the mouth and the
tongue, inferior tumor extension into this muscle raises
SCC of the Floor of the Mouth suspicion for involvement of the tongue (Figure 4-2).
The floor of the mouth is a crescent-shaped area between
the lower gingiva and the ventral surface of the tongue SCC of the Buccal Mucosa
consisting of neurovascular structures and the sublin- Buccal SCC comprises less than 10% of oral cavity
gual glands. The majority of the SCC of the floor of cancers. Similar to other subsites within the oral cav-
the mouth originate within 2 cm of the anterior mid- ity, advanced tumors involving the adjacent muscles
line floor of the mouth (Figures 4-2 and 4-6, A). These lymph nodes have poor prognostic features. Buccal SCC
tumors can invade the adjacent osseous structures and can deeply invade the neighboring structures along the
underlying soft tissues early during the course of disease parotid duct, masseter muscle, or palate, or may break
130 Section I Advanced Modalities: Protocols and Optimization

C
Figure 4-5.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 131

SECTION I
D
Figure 4-5, cont’d A 65-year-old woman recently diagnosed with tongue cancer, referred for staging with FDG PET/CT performed with
low-dose CT (upper panel), and a separately acquired contrast-enhanced high-resolution CT (lower panel). A: FDG PET/CT axial images reveal
increased FDG uptake (SUVmax 18) corresponding to a large enhancing mass involving the entirety of the mobile tongue, measuring >4 cm (T3),
and showing multiple necrotic areas on the CT portion of the study (right arrowheads; upper and lower panels). B: On the CT portion, the tumor
is noted to extend caudally to the oropharyngeal wall (small right and left arrows) and spreads to both sides of the base of tongue, oropharynx.
Tumor extension is also seen into the pterygoid muscles and in the retromolar trigone (left arrowheads). There are multiple necrotic nodes bilat-
erally in the left level II nodal regions (N2c) (large arrows). Note that the contrast-enhanced CT and PET slices do not align well due to separate
acquisition sessions (see panel B for better orientation). C: Corresponding slices of contrast-enhanced high-resolution CT and FDG PET slices
show tumor spread in the left genioglossus (large right arrows), and left myelohyoid muscles (vertical arrows). Note mildly hypermetabolic necrotic,
metastatic level II lymph nodes (left small arrows) that again do not align well with the PET slices. D: Hypermetabolic tongue mass extends crani-
ally to the left side of the nasopharynx and involves the pharyngeal recess (fossa of Rosenmüller) and palate (arrows). Note the mildly hypermeta-
bolic, necrotic left level IIB lymph node (SUVmax 3.6) (small arrows), consistent with metastatic disease. The low-grade uptake is attributable to
central necrosis. Note the value of contrast-enhanced CT for accurate staging of the primary tumor as well as necrotic lymph nodes. AJCC staging:
T3N2cMX, stage IV disease.
132 Section I Advanced Modalities: Protocols and Optimization

C
Figure 4-6 A 62-year-old woman recently diagnosed with floor of the mouth squamous cell carcinoma, referred for staging with FDG PET/
CT performed with noncontrast-enhanced low-dose CT. FDG PET/CT axial images reveal increased FDG uptake (SUVmax 18.7) corresponding to
an infiltrating tumor in the left floor of the mouth with destruction of the left symphysis and body of the mandible (T4) noted in both soft tissue
(A) and bone (B) windows. C: An enlarged hypermetabolic (SUVmax 7.9) left level IB lymph node (N1) consistent with locoregional metastatic disease
node (arrow). Note inferior border of the tumor abutting the rim of the left mandibular body (arrowhead). AJCC staging: T4N1MX, stage IV disease.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 133

SECTION I
A

B
Figure 4-7 A: A 48-year-old woman recently diagnosed with buccal squamous cell carcinoma (SCC), referred for staging with FDG PET/CT
performed with noncontrast-enhanced low-dose CT. FDG PET/CT axial images reveal a fusiform area of increased FDG uptake (SUVmax 9.5) cor-
responding to a soft tissue mass, situated in the inferior margin of the masseter muscle along the right alveolar ridge, and measuring 1.9 cm (T1),
consistent with buccal carcinoma that has infiltrated the muscle (arrow). AJCC staging: T1N0MX, stage I disease. B: A 54-year-old man recently
diagnosed with buccal SCC. FDG PET/CT performed with noncontrast-enhanced low-dose CT reveals intensely increased FDG accumulation cor-
responding to the alveolar ridge at the right mandibular angle in close proximity to the mandible (arrow) (SUVmax 14.3). Mandibular bone may be
involved; however, streak artifacts emanating from the dental implants preclude appropriate evaluation of both CT and PET images. The patient
underwent composite resection with right selective neck dissection which revealed no evidence of mandibular invasion. AJCC staging: T1N0MX,
stage I disease. Note physiologic uptake in anterior midline of oral cavity, which is usually seen at the confluence of sublingual glands and inser-
tion of the genioglossus muscle (arrowhead).

into the buccal fat pad (Figure 4-7, A). Accurate iden- c­ orresponding CT images, FDG findings can be of equiv-
tification of these areas of involvement change surgi- ocal value to both interpreting and referring physicians.
cal approach. Although MRI is ideal for imaging of the
buccal mucosa and the masticator space, PET/CT may Cancers of the Hard Palate
complement anatomic imaging with useful metabolic Dissimilar to other subsites of the oral cavity, SCC
information, particularly for lesions whose evaluation does not constitute the overwhelming majority of
is hampered by artifacts (Figure 4-7, B). Nonetheless, malignant processes of the hard palate, which is rich
streak artifacts can hinder the evaluation of FDG PET in minor salivary glands. The adenoid cystic carcinoma
and CT images alike despite appreciable FDG uptake. and mucoepidermoid carcinoma originate from the
Without the delineation of an obvious mass on the minor salivary glands, which can be found ­everywhere
134 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-8 A: A 74-year-old man with recently diagnosed palate squamous cell carcinoma (SCC), referred for staging with FDG PET/CT per-
formed with low-dose CT and a separately acquired contrast-enhanced high-resolution CT (low-dose CT not shown). FDG PET axial image reveals
increased FDG uptake (SUVmax 17.4) in a soft tissue density situated in the left anterior hard palate abutting the maxilla (arrow), consistent with
hard palate SCC. Nonetheless, diagnostic CT does not demonstrate a well-defined discrete focal mass in this location. The patient subsequently
underwent hemimaxillectomy, which revealed well-differentiated SCC of the palate. Bone and bone margins were free of carcinoma. B: 55-year-
old male presented with a mass in his left nasopharynx. FDG PET/CT performed with a contrast-enhanced high-resolution CT demonstrates a
moderately hypermetabolic (SUVmax 5.5, measured in hottest slice) well-delineated mass, measuring 3.0 cm in the left side of the nasopharynx
(arrow), extending into the palatine tonsil, consistent with the patient’s known adenocystic carcinoma. There is obliteration of the left fossa
of Rosenmüller. There is lateral displacement but no gross invasion of the adjacent pterygoid musculature. Note the difference in FDG uptake
(­SUVmax) between the tumors presented in A and B reflecting the differences in metabolic activity between SCC and adenocytic carcinoma despite
the smaller size of the palatine SCC.

in the oral cavity including the palate. Although these What Are the Oropharyngeal
tumors cannot be distinguished from SCC (Figure 4-8,
Cancer Subtypes?
A and B) by cross-sectional imaging, FDG PET meta-
bolic features display may differentiate high-grade SCC of the Base of Tongue
tumors from those of lower grade (Figures 4-8, A, The tongue base is the second most common site within
and 4-9). In low-grade malignancies, FDG uptake the oropharynx for SCC after the tonsillar SCC. Patients
with standard uptake value (SUVs) less than 4.0 may with SCC of the base of the tongue often present with
be obscured by the normal physiologic FDG uptake, advanced disease with regional lymph node metastases
particularly in organs with high background uptake (Figures 4-10 and 4-11). The base of the tongue paral-
(­Figure 4-9, A). lels the oropharyngeal posterior wall and extends to
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 135

SECTION I
A

B
Figure 4-9 A: 59-year-old man recently diagnosed with adenocystic carcinoma of the left submandibular gland. FDG PET/CT performed
with a contrast-enhanced high resolution CT demonstrates mild-to-moderately increased FDG uptake in the left mandibular gland (SUVmax
5.6; arrow). Note marginal difference in FDG metabolism between the two submandibular glands suggesting a low-grade tumor involving
the left side. B: A 66-year-old man recently diagnosed with palate squamous cell carcinoma (SCC). FDG PET/CT performed with a contrast-
enhanced high resolution CT demonstrates significantly increased FDG uptake (SUVmax 9.8) in the posterior aspect of the right palate, con-
sistent with high-grade SCC (arrows). The significant difference in FDG metabolism between the two tumor types represents the difference in
tumor grades.

the pharyngoepiglottic folds and vallecula. The anterior this region but may still be a complement in special
spread of base of the tongue SCC can involve the floor circumstances where anatomic imaging is not definitive
of the mouth (Figure 4-10, A). Tumor can also spread (Figure 4-11).
posterolaterally to the lingual and faucial tonsils or One caveat is that small lesions are difficult to detect
inferiorly to the preepiglottic fat, vallecula, epiglottis, on FDG PET imaging due to physiologic uptake within
or supraglottic larynx (Figure 4-10, B). Inferior exten- the lymphoid tissue at the base of the tongue. Although
sion of a tumor from the tongue base into the preepi- asymmetry at the base of the tongue can be a sign of
glottic fat space implies supraglottic larynx involvement pathologic process, not all asymmetries can account for
and often requires partial supraglottic laryngectomy. malignancy. Conservation therapy with chemoradia-
The accuracy of CT or MRI for determining preepiglot- tion is the standard definitive treatment of oropharyn-
tic fat infiltration is high at approximately 90%. Thus, geal cancers. Small-volume tumors can be treated with
FDG PET does not play an essential role in evaluating surgery or radiation therapy. Larger T-staged lesions are
136 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-10 A 57-year-old woman recently diagnosed with base of tongue squamous cell carcinoma, referred for staging with FDG PET/CT per-
formed with noncontrast-enhanced low-dose CT. A: Large area of increased FDG uptake (SUVmax 14.8) involving the base of tongue encompasses
both the right and left sides of the midline, measures 4.2 cm and apparently involves the extrinsic tongue muscles (T4?) in the posterior floor of
the mouth (arrows). Increased FDG uptake (SUVmax 12.8) in an enlarged left level IIA lymph node which measures 2.9 cm (N1) (small arrows).
These findings represent T4?N1MX disease, stage IV (see Figure 4-43 for further evaluation). However, the association of a contrast-enhanced CT
study would increase the accuracy and reader confidence, particularly with respect to T staging. B: The tumor extends inferiorly to the right oro-
pharyngeal wall, vallecula, and the epiglottis (arrowhead). This finding suggests supraglottic laryngeal involvement and prompts consideration of
a partial laryngectomy. The patient subsequently underwent neoadjuvant therapy with chemoradiation followed by surgical resection with partial
laryngectomy and lymph node dissection.

generally treated with concurrent chemotherapy and and hard palate (Figure 4-14, A). In cases with advanced
radiation therapy in an attempt to preserve function. tumors, invasion of the masticator and parapharyngeal
space is readily detected on FDG PET imaging.
SCC of the Tonsils Similar to base of tongue lesions, small lesions
Carcinomas that arise from the tonsillar fossa are the located within a tonsillar crypt can be undetectable
most common oral cavity cancers. The anterior and pos- on PET/CT imaging. As the tumor grows, asymmetry
terior tonsillar pillars are mucosal folds over the pala- becomes more evident. However, subtle tonsillar asym-
toglossus and palatopharyngeal muscles, respectively. metry can be present as a normal anatomic variant in
There may be inferior involvement of the tongue base normal individuals. Tonsillar asymmetry should raise
or posterior extension along the lateral oropharyngeal suspicion for tumor. However, without the presence of
wall (Figure 4-12). Anteriorly, the lesions may extend clinical symptoms (e.g., painful swallowing, ipsilateral
into the oral cavity (Figures 4-13 and 4-14). Laterally, otalgia, adenopathy), the incidence of an asymmetric
tumors may invade the parapharyngeal space or man- tonsil harboring cancer is approximately 5% (Figure
dible. Superior spread of the tumor involves the soft 4-15, A and B). If intravenous contrast is administered,
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 137

SECTION I
Figure 4-11 A 67-year-old man recently diagnosed with base of tongue squamous cell carcinoma, referred for staging with FDG PET/CT per-
formed with noncontrast-enhanced low-dose CT and a separately acquired contrast-enhanced CT study (not shown). There is increased FDG
uptake (SUVmax 9.4) in the left base of tongue (right diagonal arrows), with extension into the midline as evidenced by FDG uptake in this region
(arrowheads), tumor extent could not be assessed well on the separately acquired contrast-enhanced dedicated CT (not shown). In this case, FDG
PET complemented the findings of CT imaging, suggestive of more extensive local involvement that might lead to a change in the surgical plan.
There is also suggestion of involvement of the extrinsic tongue muscles (mylohyoid) in the posterior floor of the mouth (left small arrows). An
unenlarged hypermetabolic (SUVmax 5.4) left level IIA lymph node is suggestive of metastatic disease (arrowheads). PET findings upstaged disease
to from T1N0M0 to T1N1M0, with migration from stage I to stage III disease per clinical and CT evaluation. Lymph node metastasis was confirmed
after subsequent neck dissection.

Figure 4-12 A 57-year-old man recently diagnosed with moderately differentiated tonsil squamous cell carcinoma, referred for staging with
FDG PET/CT performed with noncontrast-enhanced low-dose CT and a separately acquired contrast-enhanced CT study (not shown). There is
increased FDG uptake (SUVmax 10.2) in the left tonsillar fossa demonstrating fullness in the oropharyngeal wall (arrows), consistent with the
patient’s known primary tumor. Note the physiologic uptake (SUVmax 2.7) in the contralateral tonsil (arrowhead). There is a subcentimeter hyper-
metabolic left level IIB lymph node (small arrows) suggestive of metastatic disease (N1) despite its small size (N0 disease by CT criteria). This
finding upstaged disease to T1N1M0, representing stage III disease rather than stage I per clinical and CT evaluation. Lymph node metastasis was
confirmed on subsequent histopathologic examination.
138 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-13 A 66-year-old woman recently diagnosed with well-differentiated tonsil squamous cell carcinoma, referred for staging with FDG
PET/CT performed with contrast-enhanced high-resolution CT. A: There is increased FDG uptake (SUVmax 12.8) corresponding to a heteroge-
neously enhancing mass in the left tonsillar fossa causing prominence of the oropharyngeal wall, measuring 3.2 cm (T2) on the accompanying
contrast-enhanced CT study (arrows), consistent with the patient’s known primary tumor. This mass extends anteriorly to invade the base of
tongue (arrowhead) but spares the genioglossus muscle (vertical arrows). B: A subcentimeter mildly hypermetabolic (SUVmax 2.7) left level IIA
lymph node (diagonal arrows) raises suspicion for metastatic disease (N1?). However, histopathologic evaluation of the neck dissection specimen
revealed no evidence of lymph node metastasis, proving the FDG PET finding as false positive. Note that inflammatory or reactive changes in
lymph nodes, particularly in those that are draining the primary tumor can cause false positive findings. AJCC staging: T2N0M0, stage II disease.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 139

SECTION I
A

B
Figure 4-14 A 59-year-old man recently diagnosed with squamous cell carcinoma (SCC) of the right tonsil, referred for staging with FDG PET/
CT performed with noncontrast-enhanced low-dose CT. A: Coronal images of the FDG PET/CT study demonstrates a large area of hypermetabolic
(SUVmax 20) conglomerate mass involves the right oropharyngeal wall and extends from the region of the right tonsil and epiglottis, consistent
with the primary tumor (4.2 cm, T3). There are multiple, enlarged, confluent lymph nodes at the levels of right IB (SUVmax 9.5, size 1.8 cm), right
IIA (SUVmax 11, size 2.2 cm), right IIB (SUVmax 6.7, size 1.47 cm), left IIA (SUVmax 13, size 2.3 cm), and left IIB (SUVmax 9.5, size 1.45 cm) with
extension into level III on the right side. B: There are lymph nodes with increased FDG uptake at the right level III (SUVmax 4.5, size 10 mm) and
left level III stations (SUVmax 6, size 7.3 mm). Subsequent lymph node biopsy revealed moderately to poorly differentiated SCC. In advanced
T-stage tumors, the likelihood of bilateral neck involvement (stage IV disease) is high.
140 Section I Advanced Modalities: Protocols and Optimization

C
Figure 4-15 A: A 47-year-old patient who presented with metastatic SCC of unknown origin in the right neck, referred for evaluation of extent
of disease and identification of the primary malignancy. PET/CT scan performed with noncontrast enhanced low-dose CT demonstrates increased
FDG uptake in a large level IIA mass showing central necrosis and only peripherally prominent FDG uptake (SUVmax 23; arrows), consistent with
metastatic disease of unknown primary. B: Asymmetric uptake in the right tonsillar fossa (SUVmax 5.6; small arrow). This finding originally was
interpreted as “consistent with the tonsillar primary SCC”; however, subsequent surgery confirmed acute tonsillitis, proving the FDG PET finding
as false positive for malignancy. C: The patient subsequently underwent chemoradiation therapy and follow-up study 3 months after completion
of definitive therapy. FDG PET study demonstrates complete resolution of the level II mass, suggestive of favorable response to therapy. Impor-
tantly, the planned lymph node dissection was deferred based on resolution of neck disease.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 141

SECTION I
A

B
Figure 4-16 A 71-year-old patient recently diagnosed with soft palate squamous cell carcinoma, referred for evaluation of extent of disease
with PET/CT study performed with noncontrast enhanced low-dose CT (A) and a separately acquired contrast-enhanced CT study (B). PET/CT
axial slices (A) and contrast-enhanced CT (B) demonstrate a large hypermetabolic (SUVmax 16) soft tissue mass involving the right palatine tonsil
extending to the soft palate (right arrows). The tumor extends across the midline and thickens the left aspect of the soft palate (small arrows). The
left tonsillar region is slightly less full, but whether tumor extends into this region is uncertain based on the CT study. However, based on the
distribution of FDG uptake, both tonsils appear involved. There is a 1.4-cm necrotic left retropharyngeal lymph node with no FDG uptake (arrow-
heads). The necrotic lymph nodes can be completely false negative on FDG PET imaging. In this case, both dedicated CT and PET complemented
each other by showing more findings together than with each test alone.

the CT portion of PET imaging demonstrates enhance- palate, but minor salivary gland cancers are not infre-
ment similar to that of the tonsils. quent. Carcinomas of the soft palate most commonly
Given the equal performance, primary radiation ther- involve the oral aspect of the palate. These lesions have
apy is the preferred treatment of choice for early tonsil- the potential to involve the tonsillar pillars and the hard
lar carcinoma due to the morbidity of surgery. The role palate (Figure 4-16) or the skull base. Minor salivary
of salvage surgery after radiation for early tonsillar carci- gland tumors (e.g., mucoepidermoid and adenoid cystic
nomas is well established. As with tumors in other oro- carcinomas) can be encountered in this area, although
pharyngeal subsites, multimodality therapy has become much less so than SCCs.
the standard of care for advanced tumors of the tonsillar Either primary surgical resection or radiation therapy
complex for superior local control. is the treatment of choice for early (T1–T2) soft palate
SCCs. Locally advanced (T3–T4) soft palate SCCs cur-
SCC of the Soft Palate rently are treated by multimodality therapy involving
The soft palate is a much less frequent subsite for SCC chemoradiation and surgery. Laser surgery, prostheses,
than are the faucial tonsils or the base of the tongue. As and microvascular free flaps have recently gained more
expected, SCC is the most common tumor of the soft momentum in designing surgical approaches.
142 Section I Advanced Modalities: Protocols and Optimization

II. WHAT ARE THE ANATOMIC structures also associated with morphologic abnor-
SUBSITES TO EVALUATE IN malities, particularly for the thyroid cartilage (Figures
LARYNGEAL CANCERS? 4-19, 4-20 and 4-21). Overall sensitivity and specific-
ity of approximately 80% were reported for the com-
There are three anatomic levels to larynx, supraglot- bination of these findings. However, it is conceivable
tis, glottis and subglottis. The cartilaginous frame of that inflammatory changes associated with the adja-
the larynx consists of the thyroid, cricoid, and aryte- cent neoplasm may cause findings similar to those of
noid cartilages. Superiorly, the epiglottis forms the direct tumor invasion leading to false-positive results,
border with the pharynx. Inferiorly, it extends to the particularly on FDG PET/CT imaging (Figure 4-22).
lower margin of the cricoid. The cricoarytenoid joint Hypopharyngeal tumors involving the piriform sinus
demarcates glottic from supraglottic and subglottic often invade the cornua and superior border of the thy-
structures. The distinction between supraglottic struc- roid cartilage (at the transition site with the thyrohyoid
tures; epiglottis, aryepiglottic folds, false vocal cords, membrane).
laryngeal ventricle, and superior superficial mucosa Other areas that affect management with respect to
of the arytenoids and glottic larynx; true vocal cords; the extent of primary tumor include the preepiglottic
and anterior and posterior commissures is crucial for and paraglottic fat planes (Figure 4-23). Invasion of
proper management. The subglottis starts below the these contiguous spaces not only increases the likeli-
level of the true vocal cords and extends to the first hood of nodal metastases but also portends potential
tracheal ring. involvement of the base of the tongue and the hyoid
bone.
Does FDG PET/CT Have a Primary
Role in the Evaluation of Primary What Are the Laryngeal Cancer
Tumor in Laryngeal Cancers? Subtypes?
Similar to oral and oropharyngeal SCCs, the deter- Supraglottic SCC
mination of T staging is based on the assessment of Supraglottic SCC accounts for 30% of laryngeal can-
depth of tumor invasion. Although endoscopic assess- cers and often are diagnosed at advanced T stages
ment is the mainstay of T staging, imaging correlates because of its insidious onset. Critical sites for assess-
are important for management. ceCT is the imag- ment include the laryngeal ventricles, arytenoids, and
ing modality of choice, with sensitivity and speci- anterior commissure, the involvement of any of which
ficity of approximately 95% and 85%, respectively. precludes supraglottic laryngectomy. These tumors pri-
FDG PET performed with noncontrast CT does not marily invade the preepiglottic space, which may lead
provide additional clinically relevant information to involvement of the anterior commissure (Figures
due to its inability to differentiate among various 4-23 and 4-24), glottis, or subglottis, and thus eventu-
depths of invasion in soft tissues. However, a baseline ally become transglottic tumors. Supraglottic tumors
FDG PET/CT acquired with intravenous contrast on originating from the false cord, laryngeal ventricle,
board considerably increases the interpretation accu- or aryepiglottic fold primarily infiltrate the paraglot-
racy of subsequent follow-up studies (Figures 4-17 tic space (Figure 4-23), the vallecula anteriorly, or the
through 4-19). pharyngeal wall laterally, or can extend into the tongue
base through the glossoepiglottic fold by submucosal
Does FDG PET Have a Role spread. Destruction of thyroid cartilage can be seen
in Evaluation of Cartilage with more advanced tumors. Infiltration of the hypo-
Involvement? pharynx is common with posteriorly situated supra-
glottic SCCs.
Cartilage invasion by laryngeal and hypopharyngeal Despite the high sensitivity of CT and MRI, the
SCCs leads to upstaging of the tumor to T4 status. Cri- specificity of anatomic imaging is limited due to peri-
coid or thyroid cartilage invasion is associated with tumoral inflammatory changes that may lead to over-
a higher recurrence risk and precludes organ-sparing estimation of tumor extent. In these situations, FDG
laryngectomy. The presence of tumor may cause new PET/CT may be helpful in increasing diagnostic cer-
bone formation and osteolysis in the adjacent carti- tainty by demonstrating increased metabolism in the
lage. However, variable ossification and chondrifica- involved regions. Nonetheless, caution still should
tion of the laryngeal cartilages render the evaluation be exercised because FDG is not specific to malignant
for tumoral involvement difficult. Thus, the patterns of processes. Severe inflammation may also cause false-
ossification caused by neoplastic growth cannot easily positive findings.
be distinguished from benign sclerotic variants. Extra-
thyroidal extension, erosion, and lysis of the cartilage Glottic SCC
occur in overt invasion of the cartilage with specificity Greater than 50% of laryngeal SCCs originate from the
greater than 90%. However, sensitivity usually is low glottic larynx. Patients present in early phases of disease
for these findings unless all coexist. FDG PET/CT imag- due to abrupt development of hoarseness. Glottic SCC
ing can increase the sensitivity of detection of cartilage typically arises from the anterior half of the vocal cord
involvement in cases with unequivocally increased glu- and spreads via the anterior commissure to invade the
cose metabolism corresponding to the cartilaginous contralateral cord or thyroid cartilage (Figure 4-25).
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 143

SECTION I
A

C
Figure 4-17 A 57-year-old woman recently diagnosed with a supraglottic squamous cell carcinoma (SCC), referred for staging with FDG
PET/CT performed with contrast-enhanced high-resolution CT. A, B: Increased FDG uptake (SUVmax 11.0) corresponds to a mildly enhancing
mass in the right supraglottic larynx involving the paraglottic fat planes (arrows) with extension into the right piriform sinus (T3) (small arrows).
C: Increased FDG uptake (SUVmax 10) in a heterogeneously enhancing right level II lymph node represents metastatic disease (N1) with suggestion
of a necrotic component. The patient underwent supraglottic laryngectomy and right selective neck dissection, which revealed invasive moderately
differentiated SCC as well as replacement of the level II lymph node by metastatic tumor causing necrotic changes but without extranodal inva-
sion. AJCC stage: T3N1MX, stage III disease.
144 Section I Advanced Modalities: Protocols and Optimization

Figure 4-18 A 65-year-old man recently diagnosed with a supraglottic squamous cell carcinoma, referred for staging with FDG PET/CT per-
formed with contrast-enhanced high-resolution CT. Axial images of a PET/CT study show increased FDG uptake (SUVmax 12.5) corresponding
to nodular thickening of the left supraglottic region (arrows) involving the preepiglottic space and the vallecula extending from the median glos-
soepiglottic fold toward the left side without fixation of the vocal cords (determined by laryngoscopy) (T3). There is no evidence of lymph node
involvement (N0). AJCC stage: T3N0MX, stage III disease.

B
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 145

SECTION I
A

B
Figure 4-20 A 74-year-old man recently diagnosed with glottic squamous cell carcinoma, referred for staging with FDG PET/CT performed
with a noncontrast-enhanced low-dose CT and separately acquired dedicated CT. A: Axial images of PET/CT study demonstrate a hypermetabolic
(SUVmax 9.5) enhancing mass mainly involving the right vocal cord (arrows) extending across the anterior commissure to involve the anterior half
of the left vocal cord. B: Bone windows of the dedicated CT study demonstrate complete destruction/lysis of the right anterior aspect of the thyroid
cartilage (T4) (arrowheads). There is no evidence of metastatic cervical lymph nodes. AJCC stage: T4N0MX, stage IV disease.

Figure 4-19 A 63-year-old man recently diagnosed with glottic squamous cell carcinoma, referred for staging with FDG PET/CT performed with
contrast-enhanced high-resolution CT. A: Axial images of PET/CT study demonstrate an intensely hypermetabolic (SUVmax 22) enhancing mass
centered on the left true vocal cord, involving the anterior commissure and apparent extension into the anterior third of the right true vocal cord
with fixation of the vocal cord (determined by laryngoscopy) (T3) (arrow). B: Bone windows demonstrate that FDG uptake also extends into the
left thyroid cartilage, which shows subtle erosion with sclerotic and lytic changes on the accompanying CT (small arrows), consistent with cartilage
involvement. There is no evidence of metastatic cervical lymph nodes. AJCC stage: T4N0MX, stage IV disease.
146 Section I Advanced Modalities: Protocols and Optimization

B
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 147

Figure 4-21 A 52-year-old man recently diagnosed with glottic squamous cell carcinoma, referred for staging with FDG PET/CT performed with

SECTION I
a noncontrast-enhanced low-dose CT and a separately acquired contrast-enhanced CT study. A: Axial images of PET/CT study demonstrate a bulky
hypermetabolic (SUVmax 26) mass extending from the left supraglottic region (upper panel, arrows). At the level of the true cords, it appears to
extend across the anterior commissure to involve the anterior right true vocal cord (lower panel, arrows). B: The tumor extends through the level
of vocal cords and involves the subglottic larynx, and the thyroid cartilage anteriorly (arrows). FDG PET image shows definite evidence of involve-
ment by tumor, although the findings on the accompanying CT are subtle with no frank cartilage destruction (lower panel, bone windows).
Histopathology revealed cartilage invasion proving the CT to be false negative. AJCC stage: T4N0MX, stage IV disease.

B
Figure 4-22 A 61-year-old man recently diagnosed with supraglottic squamous cell carcinoma, referred for staging with FDG PET/CT per-
formed with contrast-enhanced high-resolution CT. A: Axial images of PET/CT study demonstrate a hypermetabolic mass (SUVmax 11.3) involving
the right side of the supraglottic larynx effacing the paraglottic fat plane, posteriorly. The tumor involves the right arytenoid and appears to extend
through the apex of the piriform sinus (arrows) with cord fixation (determined by laryngoscopy) (T3). B: Although the tumor appears to be close
to the right thyroid cartilage on FDG PET imaging, the bone windows of the diagnostic CT study reveal no evidence of thyroid cartilage involve-
ment (arrows). There is no evidence of metastatic cervical lymph nodes. AJCC stage: T3N0MX, stage III disease.
148 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-23 An 88-year-old man recently diagnosed with transglottic squamous cell carcinoma involving both supraglottic and glottis larynx,
referred for staging with FDG PET/CT performed with noncontrast-enhanced low-dose CT. A: Axial images of PET/CT study demonstrate a large
hypermetabolic (SUVmax 17.8) predominantly supraglottic tumor involving the right vallecula, aryepiglottic folds, and paralaryngeal fat. B: Tumor
extends to involve the right glottis with vocal cord fixation as well as the surrounding right arytenoid cartilage (T3) (arrows). A nodular compo-
nent in the anterior commissure extends slightly to the anterior left glottis. Tumor abuts a large portion of the right thyroid cartilage but does not
involve it (bone windows not shown). There is a 1.0-cm left level III lymph node with mild FDG uptake (SUVmax 2.6) (arrowheads) that may be
either metastatic or reactive in nature (N1 vs N0). AJCC stage: T3N0 or N1MX, either setting stage III disease. The patient underwent neoadjuvant
therapy with chemoradiation followed by resection and elective lymph node dissection. The level III lymph node was negative for tumor but there
was suggestion of treated tumor on histology (see Figure 4-45 for M staging).
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 149

SECTION I
Figure 4-24 A 60-year-old man recently diagnosed with supraglottic squamous cell carcinoma (SCC), referred for staging with FDG PET/CT
performed with contrast-enhanced high-resolution CT. Axial images of PET/CT study demonstrate a hypermetabolic (SUVmax 12.7) soft tissue mass
involving the right vocal cord invading the anterior commissure (arrow) suggestive of involvement of the contralateral site. Subcentimeter lymph
nodes in level III stations, bilaterally, demonstrate increased FDG uptake (small arrows) (SUVmax 3.7) and are suspicious for metastatic foci regard-
less of their small size. The patient underwent neoadjuvant therapy followed by total laryngectomy and lymph node dissection, which revealed
poorly differentiated SCC. On histopathology, the level III lymph nodes revealed metastatic disease. AJCC stage: T3N2cMX, stage IV disease.

Once the tumor reaches the anterior commissure, it peritumoral inflammatory changes make it difficult to
may easily spread into the supraglottis or subglottis and accurately determine the exact tumor extent for both
become transglottic. Of note, the term transglottic car- anatomic and FDG PET imaging.
cinoma generally refers to tumors that involve both the
glottis and supraglottis. Transglottic extension is critical Subglottic SCC
for the surgical approach as transglottic involvement Involvement of the subglottis by laryngeal cancer usu-
implies advanced disease and an unfavorable progno- ally represents inferior spread of a glottis or supraglottic
sis. Transglottic tumors, particularly those that spread tumor rather than a primary tumor originating in the
­vertically in the anterior midline, have a tendency to subglottis. True subglottic SCCs account for only 5% of
invade the laryngeal framework and cricothyroid mem- laryngeal SCCs and are highly aggressive with a poor
brane. Vocal cord fixation usually is determined by prognosis. These tumors subclinically advance to late
endoscopic examination and indicates at least T3 tumor, stages with invasion of the surrounding structures, not-
which requires T3 combination chemoradiotherapy in withstanding the relative paucity of lymphatic drainage
an effort to prevent the morbidity associated with total in this region. Subglottic SCC can spread into the true
laryngectomy. cords, supraglottis, and trachea, or through the crico-
At initial staging, in an untreated patient, the anterior thyroid membrane into the thyroid gland or posteriorly
commissure should have no FDG uptake and no soft tis- into the esophagus.
sue present in the interthyroidal notch on the accompa-
nying CT study. Even a small degree of FDG uptake in the HYPOPHARYNGEAL CARCINOMA
opposite cord should raise suspicion for tumor spread
to the contralateral site. If the FDG PET is accompanied Hypopharynx is defined as is the region between the
by ceCT, soft tissue thickening of the anterior commis- oropharynx at the level of the hyoid bone and the
sure should increase the confidence of interpretation esophagus at the lower end of the cricoid cartilage.
(Figure 4-25). Glottic tumors can invade the thyroid Most hypopharyngeal SCCs (~70%) arise from the
cartilage superiorly into the paraglottic space (Figures piriform sinus (Figure 4-26), but they can also involve
4-19 through 4-21), inferiorly into the subglottic space, the lateral pharyngeal wall (25%), posterior pharyn-
and posteriorly into the posterior commissure, aryte- geal wall, or postcricoid pharynx (5%). Most patients
noid cartilage, cricoid cartilage, or cricoarytenoid joint. present with large T3 or T4 tumors. Tumors originat-
Subglottic involvement and cricoid cartilage invasion ing from the lateral wall of the piriform sinus infiltrate
necessitate total laryngectomy. Posterior glottic tumors toward the common carotid artery. Tumors involving
are rare. These tumors may invade the cricoarytenoid primarily the medial wall of the pyriform sinus ­usually
cartilage and piriform sinus, thereby gaining access to infiltrate the aryepiglottic folds and can invade the
its lymphatic drainage. Subglottic spread is commonly laryngeal framework by involving the paraglottic space.
seen. The sensitivity of CT and MRI to detect subglot- Tumors of the lateral wall and apex commonly invade
tic involvement is higher than endoscopic biopsy, but the thyroid cartilage.
150 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-25 A 58-year-old man recently diagnosed with transglottic squamous cell carcinoma involving both the supraglottic and glottis lar-
ynx, referred for staging with FDG PET/CT performed with contrast-enhanced high-resolution CT. A: Axial images of PET/CT study demonstrate
a hypermetabolic (SUVmax 9.4) mass in the supraglottic larynx extending from the preepiglottic space to the right paraglottic space (arrows).
B: Caudally, the mass appears to extend into the anterior commissure (arrows) and possibly involves the anterior aspect of both true vocal cords
without fixation of the cords (determined by laryngoscopy) (T2). There is no erosion of the laryngeal cartilages, no extension of the tumor outside
of the laryngeal superstructure, and no evidence of lymph node involvement. AJCC stage: T2N0cMX, stage II disease.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 151

SECTION I
A

B
Figure 4-26 A 61-year-old man recently diagnosed with hypopharyngeal squamous cell carcinoma (SCC), referred for staging with FDG PET/
CT performed with contrast-enhanced high-resolution CT. A: Axial images of PET/CT study show a mass involving the right side of the hypophar-
ynx extending toward the midline, measuring 2.1 cm. The tumor invades the supraglottic larynx, extends around the right arytenoid, and appears
to extend through the apex of the piriform sinus (T2) (arrows). There is no evidence of lymph node involvement (N0). B: A 70-year-old man with
a recent diagnosis of hypopharyngeal SCC, referred for staging with FDG PET/CT performed with contrast-enhanced high-resolution CT. Axial
images of PET/CT study demonstrate a large hypopharyngeal soft tissue mass with heterogeneous enhancement and intense FDG uptake (SUVmax
22) measuring 3.1 cm (T2) (arrows). Additionally, there is an enlarged hypermetabolic (SUVmax 15) right level III lymph node measuring 2.7
cm (N1) (small arrows), consistent with metastatic disease. The patient subsequently underwent chemotherapy and hyperfractionated radiation
therapy, followed by selective neck dissection. The patient responded well to therapy with no evidence of residual disease at 8-month follow-up,
which included repeat PET/CT and diagnostic CT studies.
152 Section I Advanced Modalities: Protocols and Optimization

Figure 4-27 A 58-year-old man recently diagnosed with base of tongue squamous cell carcinoma, referred for staging with FDG PET/CT per-
formed with noncontrast-enhanced high resolution CT. Axial images of PET/CT study demonstrate a hypermetabolic (SUVmax 13.4) mass, mea-
suring 2.0 cm (T1) in the left base of tongue extending to the midline, consistent with the patient’s known primary tumor (arrowheads). There is
a 1.0-cm hypermetabolic (SUVmax 7.0) left level IIA lymph node (arrows), consistent with metastatic disease regardless of its small size based on
the intense FDG uptake. This PET finding upstaged disease from T1N0M0 to T1N1M0, with migration from stage I to stage III disease per clinical
and CT evaluation. Subsequent histopathology confirmed lymph node metastasis.

DOES FDG PET/CT HAVE A metastasize to lymph node levels I to III (Figures 4-5
PRIMARY ROLE IN EVALUATION and 4-28); thus, selective neck dissection is the proce-
OF REGIONAL LYMPH NODE dure of choice for management of the neck.
METASTASES? The major lymphatic drainage of the oral tongue
(anterior two thirds of the tongue) is to level I to
In HNSCC, the most important prognostic factor is II lymph nodes, often with bilateral involvement.
locoregional lymph node involvement, which deter- Patients with tongue SCC can present with level IIB
mines the subsequent elective treatment of the neck metastases, although this sublevel of involvement
(Table 4-1). Cervical lymph nodes are grouped into is rare in oral cavity SCCs (Figure 4-5, C). Isolated
levels I through VI. CT and MRI interpretation depends metastases to level IV, known as “skip metastases,”
on size criteria, whereas FDG PET reading is dictated can also occur in tongue SCC. In large tumors (Fig-
by metabolic characteristics of the lymph nodes. Gen- ure 4-14) and those crossing the midline, the chance
erally, for level I to II lymph nodes, a measurement for bilateral lymph node involvement is significantly
≥1.5 cm in the greatest dimension and ≥0.8 mm for high.
retropharyngeal lymph nodes and >1.0 cm for all other The floor of the mouth SCC frequently metastasizes
neck nodes is the established definition for lymphade- to the lymph nodes due to the absence of a fascial bar-
nopathy. However, FDG PET can demonstrate uptake rier with free communication between the submandibu-
in normal-sized lymph nodes, implying metastatic lar space, sublingual space, and inferior parapharyngeal
disease and thereby increasing the detection sensitivity fatty space. Commonly, metastasis occurs to level I and
by 10% to 30% compared to ceCT (Figures 4-11, 4-13, II lymph node basins (Figure 4-6, C). As many as 20% of
B, 4-24, and 4-27). More specifically, the sensitivity patients with greater than T1 lesions have occult lymph
and specificity of FDG PET in detecting cervical nodal node metastasis, and elective neck dissection with
disease ranges from 74% to 94% and 82% to 100%, adjuvant radiotherapy may be necessary for increased
respectively, compared to CT, which ranges from 65% regional control.
to 81% and 47% to 81%, respectively. Of note, FDG The rich lymphatic network of the buccal region
PET/CT has been shown to be useful in detecting results in lymph node metastasis in a high number of
nodal metastases in patients with more advanced T patients, essentially involving levels I to III. In contrast,
stages when nodal disease is more likely (Figure 4-5). minor salivary gland tumors of the hard palate usually
do not metastasize to the neck, obviating the need for
Oral Cavity SCC neck dissection in clinically negative cases. In the case of
Cervical lymph node metastases are common and occur metastatic disease, SCCs of the hard palate metastasize
in nearly half of patients who present with oral cavity to level I cervical lymph nodes, particularly in patients
SCCs. This group of cancers has a high propensity to with stage T2 or higher tumors.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 153

SECTION I
A

B
Figure 4-28 A: A 65-year-old woman recently diagnosed with squamous cell carcinoma of the tongue, referred for staging with FDG PET/CT
performed with noncontrast-enhanced low-dose CT. A: Axial images of PET/CT study demonstrate a hypermetabolic mass (SUVmax 18) on the
lateral aspect of the left tongue (arrowheads), consistent with the patient’s primary disease. There are bilateral, multiple, prominent, hypermeta-
bolic (SUVmax 10.2) lymph nodes involving the level IIA (small arrowheads), consistent with bilateral lymph node metastases (N2c) B: Additional
hypermetabolic lymph nodes are noted in levels IB (arrows) and III (small arrowheads) (SUVmax 8.0), consistent with additional metastatic disease
(N2c). The major lymphatic drainage of the oral tongue is to levels I and II lymph nodes, often with bilateral involvement. Level III lymph nodes
may also be involved in advanced cases.

Oropharyngeal SCC node metastases, primarily to levels II through IV lymph

Regional lymph node metastases are seen even more nodes (Figures 4-3, 4-10, and 4-11). Even early T-stage
frequently in oropharyngeal SCC patients at the time lesions typically present with cervical metastasis in
of diagnosis, with rates exceeding 50%. Bilateral neck close to one fourth of patients who present with bilat-
involvement occurs in 15% of patients with cervical eral neck involvement. Tongue base carcinoma may also
metastases. Lymphatic drainage from the oropharynx is extend laterally to encase the internal carotid artery,
often directed to level II to III cervical nodes and may upstaging the tumor to stage IVB and making the tumor
also involve level I cervical and retropharyngeal lymph unresectable.
nodes, with level II being the most commonly involved In tonsillar SCCs, clinically positive nodal metas-
subsite (Figures 4-1, 4-3, 4-11, and 4-12). In the previ- tases are common at the time of diagnosis in nearly
ously untreated neck, metastases to level IV or V are rare three fourths of patients (Figures 4-1 and 4-12). These
in the absence of obvious lymphadenopathy at levels metastases usually are ipsilateral, although contralat-
I to III. Systematic reviews have shown that sublevel eral nodal disease has been reported in 20% of patients.
IIB metastases are rare in oral cavity SCC (Figures 4-1 The most frequently involved site is the level II lymph
and 4-12). node basin, which may extend to the level III region.
The base of tongue has rich lymphatic drainage with Predominantly cystic SCC metastasis in the neck can be
significant cross-drainage, resulting in up to 40% of seen with palatine and lingual tonsil tumors. Such cystic
patients presenting with contralateral cervical lymph metastases may not be differentiated from ­liquefaction
154 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-29 A 66-year-old woman recently diagnosed with carcinoma of unknown primary (CUP) of the right neck, referred for determination
of the primary and evaluation of extent of disease with FDG PET/CT performed with contrast-enhanced high-resolution CT. A: Axial images of
PET/CT study demonstrate a heterogeneously enhancing hypermetabolic (SUVmax 11) mass in the right level IIA region (arrows), consistent with
the patient’s known metastatic disease of unknown origin. B: There is asymmetric uptake in the right tonsil compared to the left (SUVmax 5.8 vs
2.0), suggestive of the primary disease site (arrowheads). The subsequent biopsy proved this interpretation accurate. Note that no definite mass is
demonstrated on the accompanying contrast-enhanced CT scan in the right tonsillar fossa. In patients with CUP, meticulous investigation of the
ipsilateral tonsil should be pursued due to the characteristic lymphatic drainage network.

necrosis, which can occur in solid adenopathy by imag- Soft palatal carcinomas have a high incidence of
ing modalities. These primary tumors arise in the tonsil- nodal metastasis involving levels II, III and retropha-
lar crypts and are of the transitional type rather than the ryngeal lymph node stations (Figure 4-16, B). Approxi-
usual SCC. In a patient with cystic level II nodal metas- mately 60% of patients have nodal disease at the time
tasis, the ipsilateral tonsil should be targeted for further of diagnosis. Prognoses of soft palate carcinomas are
investigation to diagnose the occult tumor. A caveat related to the extent of nodal disease, which is in return
associated with tonsillar carcinoma is metastatic SCC related to T stage.
of unknown origin involving level I through III cervical
lymph nodes. In these cases, ­meticulous ­investigation Laryngeal SCC
of the ipsilateral tonsils should be pursued due to the Primary lymphatic spread of supraglottic carcino-
­typical lymphatic drainage network (Figures 4-15, 4-29, mas is directed toward level II to III lymph nodes.
and 4-30). The differential diagnosis includes lympho- Lymph node metastases are common and often bilat-
mas of the tonsils, whose imaging features are similar eral (­Figures 4-17, C, 4-24, and 4-32). The glottis has
to those of SCC (Figure 4-31). sparse ­lymphatic drainage; thus, nodal metastases
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 155

SECTION I
A

B
Figure 4-30 A 69-year-old man recently diagnosed with carcinoma of unknown primary in the right neck, referred for determination of the
primary and evaluation of extent of disease with FDG PET/CT performed with contrast-enhanced high-resolution CT. A: Axial images of PET/
CT study demonstrate a heterogeneously enhancing hypermetabolic (SUVmax 15) mass in the right level IIB region (arrows), consistent with the
patient’s known metastatic disease of unknown primary. Asymmetric uptake in the right base of tongue/tonsillar fossa is suggestive of primary
disease (small arrowheads). The patient underwent panendoscopy and right neck dissection, which proved the right tonsil to be the primary site
of disease. B: The patient underwent chemoradiotherapy. PET/CT study 2.5 months after completion of therapy reveals complete resolution of
disease. Note residual soft tissue fullness on the CT study (arrows) consistent with fibrotic changes.
156 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-31 A: A 49-year-old man recently diagnosed with oropharyngeal squamous cell carcinoma, referred for evaluation of extent of disease
with FDG PET/CT performed with contrast-enhanced high-resolution CT. Axial images of PET/CT study demonstrate asymmetric fullness in the
right Rosenmüller fossa corresponding to a heterogeneously enhancing hypermetabolic mass (SUVmax 9.4) (arrows), consistent with a oropha-
ryngeal tumor. B: A 43-year-old man recently diagnosed with Burkitt lymphoma of the left tonsil. Axial images of PET/CT study demonstrate
asymmetric fullness in the left Rosenmüller fossa corresponding to a heterogeneously enhancing hypermetabolic (SUVmax 11.9) (arrows) mass,
consistent with lymphoma.

occur in less than 10% of patients with truly confined Hypopharyngeal SCC has a high propensity for lym-
glottic tumors. Once the tumor has traversed the crico- phatic invasion because of the abundant lymphatics in
thyroid membrane, however, the frequency of lymph the region and the extent of primary tumor, with 50%
node metastases increases significantly. Transglot- to 75% of patients presenting with nodal metastases
tic carcinoma is often accompanied by lymph node at the time of diagnosis, mainly involving level II, III,
metastases (Figure 4-23). Subglottic SCC or subglot- IV, retropharyngeal, and less frequently level V basins
tic extensions of a glottic cancer are associated with (Figures 4-26, B, and 4-33). Occult cervical lymph node
a high incidence of cervical lymph node metastases. metastases are also common, with the overall incidence
The primary drainage is directed toward levels III and of cervical lymph node metastases at presentation of
IV and less commonly to the delphian node. Subse- approximately 75%. SCC can harbor malignancy in
quently, pretracheal and paratracheal lymph nodes small lymph nodes, making FDG PET valuable in tumor
can be involved. staging.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 157

SECTION I
Figure 4-32 A 53-year-old man recently diagnosed with supraglottic squamous cell carcinoma, referred for determination of extent of disease
with FDG PET/CT performed with contrast-enhanced high-resolution CT. Axial images of PET/CT shows intense FDG uptake (SUVmax 7.3), corre-
sponding to a soft tissue fullness that is centrally located in the supraglottic larynx involving the pre-epiglottic fat, anteriorly as well as the aryepi-
glottic folds and piriform sinuses, posteriorly (arrows). This finding is consistent with the patient’s known primary tumor. Bilateral hypermetabolic
(SUVmax right 4.4, left 6.3) lymph nodes involve the right and left level III regions (small arrows) consistent with metastatic disease (N2c), which
was proven by a subsequent neck dissection.

Figure 4-33 A 61-year-old man recently diagnosed with hypopharyngeal squamous cell carcinoma (same patient as shown in Figure 4-26, A).
Axial images of PET/CT study demonstrate increased uptake in a right level IIB lymph node (SUVmax 4.7) (arrows). Although this lymph node
appears to be benign based on its morphology (smooth margins, no infiltration of the fat, and longer than wider) on the accompanying contrast-
enhanced high-resolution CT, subsequent biopsy revealed metastatic disease.

about twofold higher than that of CT or MRI (Figures

Do FDG PET and ceCT Complement 4-11, 4-12, 4-24, 4-27, 4-32, and 4-33). ­Ideally, both
Each Other in Evaluating Nodal PET and ceCT data should contribute equally to the
interpretation of PET/CT. For example, a node that has
Status?
increased in width but still is smaller than predefined
The overall accuracy of PET/CT can be significantly size limits or with evidence of central necrosis despite
higher than that of CT or MRI for the neck on a level-by- low levels of FDG uptake should be considered as har-
level basis due to enhanced sensitivity rather than speci- boring metastatic disease (Figures 4-5, C, 4-16, B, and
ficity. For example, in oral cancer SCC, on a level-by-level 4-34). Regardless of FDG PET findings, extracapsular
basis, the sensitivity of FDG PET for nodal metastases is spread is suggested by stranding at the nodal margins.
158 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-34 Two patients recently diagnosed with tonsillar squamous cell carcinoma. A: Axial slice of PET/CT study with contrast-enhanced
high-resolution CT. A centrally hypodense right level IIB lymph node demonstrates mild peripheral enhancement on contrast-enhanced study and
only mildly increased FDG uptake (SUVmax 2.1) on the FDG PET portion of the study (arrows). This finding is consistent with a necrotic lymph
node with metastatic disease. Note that the primary tumor is not included in the presented PET/CT slice. B: Axial slice of PET/CT study performed
with non-contrast enhanced low-dose CT. The primary tumor in the left tonsillar fossa (arrowheads) demonstrates increased FDG uptake (SUVmax
10) corresponding to a soft tissue density. Note the difficulty in delineating the soft tissue mass due to lack of intravenous contrast. There is a
heterogeneously attenuating enlarged left level IIA lymph node (arrows) with negligible FDG uptake (SUVmax 1.4). This finding is consistent with
a necrotic metastatic lymph node, which was confirmed by a separately acquired contrast-enhanced CT study (not shown). For both cases, without
the help of contrast-enhanced CT study, determination of a metastatic lymph node would prove challenging on the FDG PET portion of the study
and sometimes can be completely false negative.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 159

SECTION I
A

B
Figure 4-35 A 73-year-old man with a history of tonsillar squamous cell carcinoma, status post primary therapy, referred for determination of
extent of disease with FDG PET/CT performed with contrast-enhanced high-resolution CT. A: Six-month follow-up PET/CT study demonstrates
increased FDG uptake (SUVmax 4.9) corresponding to a left level III lymph node that shows benign morphologic features (smooth margins, no
infiltration of the fat, and longer than wider) (vertical arrows). This finding may represent metastatic disease, although a reactive lymph node can-
not be excluded. B: Nine-month follow-up PET/CT study demonstrates slightly decreased FDG uptake (SUVmax 3.8) and slight decrease in size of
the lymph node (vertical arrows). Provided the patient had not received any interim therapy, these findings are consistent with reactive changes
within this lymph node. When evaluating FDG PET studies, false-positive results seen in reactive lymph nodes must be considered.

­ ncasement of the carotid artery with more than 270

E (see the section How Do the Cervical Lymph Nodes
degrees of circumference is an ineligibility criterion Cause False-Positive Readings? for further discussion).
for surgery and significantly increases the risk of recur-
rence. When evaluating FDG PET studies, false-positive Does Use of Semiquantitative
results seen in reactive lymph nodes must be considered PET Methods Help in Defining
(Figures 4-13, B, 4-35, and 4-36, B). a Pathologically Positive Lymph
Node?
Does Reactive Lymphoid
Hyperplasia Pose Challenges SUVs have been helpful to a certain extent (Figures 4-11
to Classification of Lymph Node through 4-13, 4-24, 4-27, 4-35, and 4-36) in differenti-
ating benign from malignant tumors but have not defin-
Status?
itively solved the problem. In one study, according to
PET/CT fusion may increase specificity of FDG/PET receiver operating characteristic analysis, the size-based
(Figures 4-11, 4-12, 4-24, and 4-27) but cannot prevent SUVmax cutoff values of 1.9, 2.5, and 3.0 for lymph
misclassification of lymph node status when reactive nodes measuring <1.0 cm, 1.0 to 1.5 cm, and >1.5 cm,
lymphoid hyperplasia is present (Figures 4-13, B, 4-35, respectively, yielded 79% sensitivity and 99% specific-
and 4-36). Overexpression of the glucose transporter ity for nodal level staging. In another study, the sensitiv-
protein GLUT1 in the lymph nodes can be held account- ity and specificity for neck nodal staging were 75% and
able for preferential FDG uptake in reactive lymph nodes 94%, respectively, with a cutoff value of 3.5. However,
160 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-36 A 53-year-old man recently diagnosed with base of tongue squamous cell carcinoma, referred for determination of extent of dis-
ease with FDG PET/CT performed with noncontrast enhanced low-dose CT. A: Axial images of PET/CT study shows intense FDG uptake (SUVmax
16.3), corresponding to a soft tissue mass in the left base of tongue, consistent with primary tumor (arrows). There is increased FDG uptake
(SUVmax 10.4) in an enlarged left level IIA lymph node (arrowheads), measuring 1.8 cm in long axis, most consistent with locoregional metastatic
disease. B: There is also increased FDG uptake in a left level III lymph node (SUVmax 1.8), measuring 1.0 cm in long axis and showing benign mor-
phology (smooth margins, no infiltration of the fat) (small arrows), which may represent a reactive lymph node considering both the low-grade
FDG accumulation and CT features. However, these characteristics may be misleading in many other cases with metastatic disease. False-positive
results may be unavoidable in many circumstances because of lack of clear-cut definition of lymph node metastasis by PET criteria and the rela-
tively nonspecific nature of FDG uptake.

SUVs are highly variable in uncontrolled conditions ­ anagement until sufficient data accumulate to estab-
m
because they depend on a host of variables, such as lish it as a diagnostic criterion.
body fat, insulin and glucose levels, wait time, recon-
struction algorithms, and lesion size (partial volume What Is Clinically N0 Neck?
averaging). The pervasiveness of false-positive results
associated with FDG PET imaging can be alleviated Across all subsites and T stages, occult cervical metas-
to a great extent by integration of PET and CT, which tasis occurs in 10% to 50% of HNSCC patients, partic-
improves the positive predictive value (PPV) with ularly in those with oral cavity cancers. Because most
the help of precise anatomic definition. It should be of N0 neck metastases harbor microscopic tumor foci,
emphasized that for both oral and laryngeal SCCs, they may go undetected in up to 70% of cases using
no validated SUV threshold has been determined to currently available anatomic and metabolic imaging
differentiate benign from malignant nodal disease. modalities alike due to resolution limits. Therefore,
Hence, SUVs should not be used in routine clinical all patients with oral and oropharyngeal SCC should
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 161

SECTION I
Figure 4-37 A 68-year-old man with floor of mouth squamous cell carcinoma (SCC), referred for determination of extent of disease with
FDG PET/CT performed with contrast-enhanced high-resolution CT. Axial images of PET/CT study demonstrate increased FDG uptake (SUVmax
17.5) corresponding to a soft tissue mass in the anterior floor of mouth, invading the anterior mandible, displaying destructive changes on the
companion contrast-enhanced CT slice in both the soft tissue (A) and bone (B) windows (arrows). If sufficiently large, floor of mouth SCC often
involves the mandible.

be considered candidates for regional nodal therapy, (Figure 4-37), and those with palate cancers, invasion of
such as radiotherapy or elective neck dissection. The the maxilla, palatal bone, and nasal vault should be ruled
management approach to N0 disease is not universal. out (Figures 4-38 and 4-39). Although the periosteum
Some groups support observation only, and whereas serves as an early and effective barrier against bone inva-
others advocate a more aggressive surgical approach. sion in edentulous patients, tumor cells gain entrance to
the mandible through dental pits or mental or mandibu-
Does FDG PET Guide the Surgeon lar canals. Tumors of the palate can vertically invade the
nasal vault or maxillary sinus, thus requiring resection of
in N0 Neck?
underlying bone and deeper structures as necessary.
One consequence of the innate limitations of image res- The poor sensitivity associated with preoperative imag-
olution associated with PET/CT imaging (at ~6–7 mm) is ing (both FDG PET and anatomic imaging) has decreased
its suboptimal capability to detect N0 disease. This limi- reliance on imaging as the primary method for deter-
tation is heightened even more given that nearly 50% mining mandibular invasion. Currently, even with an
of metastatic cervical lymph nodes measure less than 7 effective preoperative imaging strategy, the decision for
mm in diameter. In a meta-analysis, Kyzas et al found an segmental mandibulectomy is clinically made based on
overall FDG PET sensitivity of 79% in detecting cervical tumor depth and proximity to the mandible. In general,
nodal metastases; however, the sensitivity decreased to tumor invasion of the cortex or periosteum can be man-
50% for clinically N0 patients. Yamazaki et al reported aged with marginal resection, whereas involvement of
that metastatic nodes measuring 1 cm or greater in the the medullary bone requires segmental resection. Diag-
short axis can be detected at a high rate close to 100%, nosis of unequivocal invasion of the bone requires seg-
whereas nodes smaller than 5 mm go undetected. Despite mental resection (Figure 4-37), whereas close proximity
its better performance compared to conventional imag- to the mandible or maxilla even without invasion usually
ing modalities (Figures 4-12, 4-24, 4-27, 4-32, and 4-33) is treated with marginal resection of the bone (Figures
and some promising reports with sensitivities of greater 4-2, 4-39, and 4-40).CT with contrast enhancement is the
than 75%, FDG PET still is not sufficiently sensitive to most widely used imaging technique, with a higher speci-
allow the surgeon to determine which patients will ben- ficity than sensitivity of 80% to 95%. MRI apparently is
efit from neck dissection. Furthermore, false-positive superior for evaluating invasion of the medullary cavity
results can occur due to reactive changes that occur in of the mandible, but its specificity is approximately 50%
the draining lymph nodes (Figures 4-13, B, and 4-36, B). due to false-positive findings. PET/CT imaging in con-
junction with ceCT can be helpful in delineating man-
IS FDG PET USEFUL IN dibular involvement by increasing the sensitivity and
EVALUATION OF BONE certainty in equivocal cases. One study reported a supe-
rior sensitivity for FDG PET compared to CT (100% vs
INVASION?
33%) but an inferior specificity at 85% versus 100% in
An important clinical concern is the possibility of bone identifying mandibular invasion. The suboptimal speci-
invasion, especially mandibular and maxillary invasion. ficity of FDG PET imaging can be attributed to false-pos-
In patients with oral cavity and oropharyngeal SCCs itive findings in inflammatory processes (Figure 4-41, A)
involving the floor of the mouth, retromolar trigone, or as well as a scattering of ­photons from the avidly positive
lower alveolus, tumors with mandibular involvement primary tumor into the adjacent structures (Figure 4-42).
162 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-38 A 65-year-old woman recently diagnosed with tongue cancer (same patient as shown in Figure 4-5), referred for determination
of extent of disease with FDG PET/CT performed with low-dose CT study (A). In addition, contrast-enhanced high-resolution CT was separately
obtained (B). Axial images of PET/CT study demonstrate increased FDG uptake (SUVmax 18) corresponding to a soft tissue mass involving the
tongue with extension to the oropharyngeal wall and left retromolar trigone. The tumor abuts the left maxillary tuberosity, which shows erosion
on bone windows of the contrast-enhanced CT study (arrowheads). The uptake extending into this region on the PET/CT images increases the con-
fidence of CT interpretation of bone involvement or vice versa. On CT, the left mandibular ramus is in close proximity to the tumor but shows no
evidence of erosion, consistent with sparing of the mandible. There are bilateral level II lymph nodes with increased FDG uptake consistent with
metastatic disease (N2c) (arrows). The patient underwent chemoradiation therapy followed by glossectomy and bilateral lymph node dissection
of partial maxillectomy, which confirmed maxillary bone invasion.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 163

SECTION I
A

B
Figure 4-39 A 74-year-old man with recently diagnosed palate squamous cell carcinoma (same patient as shown in Figure 4-8, A). A: Hyper-
metabolic mass (SUVmax 17.4) in the left anterior hard palate abuts the maxilla (arrowheads). B: On separately acquired diagnostic CT (bone
windows), there is no clear evidence of osseous involvement (small arrows). Evaluation of the CT study is limited due to artifacts emanating from
dental fillings. The patient subsequently underwent hemimaxillectomy, which revealed no evidence of the bone involvement. The diagnosis of
unequivocal invasion of the bone requires segmental resection. The close proximity to the mandible or maxilla even without invasion usually is
treated with marginal resection of the bone.
164 Section I Advanced Modalities: Protocols and Optimization

Figure 4-40 A 48-year-old woman recently diagnosed with buccal squamous cell carcinoma (same patient as shown in Figure 4-7, A). Hyper-
metabolic mass (SUVmax 9.5) in the right alveolar ridge abuts the mandible, although with no clear evidence of osseous involvement on the bone
windows of the accompanying CT study (arrowheads). The patient underwent a partial mandibular resection, which revealed no bone involvement
on the tumor specimen.

A
Figure 4-41 A 77-year-old man with a diagnosis of right base of tongue squamous cell carcinoma, referred for FDG PET/CT study performed
with noncontrast enhanced low-dose CT study for evaluation of the disease status 3 months after completion of chemoradiation. A: Axial images
of PET/CT study demonstrate increased FDG uptake (SUVmax 9.5) corresponding to the right angle of the mandible (arrowheads), raising suspicion
for disease recurrence, although there is no pathologic finding on the accompanying CT study. Subsequent biopsy revealed acute inflammation of
the gum line with no evidence of malignancy.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 165

SECTION I
B
Figure 4-41, cont’d B: Three-month follow-up PET/CT study revealed resolution of the previously increased FDG uptake. This finding may
represent radiation-related inflammatory epithelial changes. Note the physiologic uptake in the anterior midline of the oral cavity, which usually
is seen at the confluence of sublingual glands and the insertion of the genioglossus muscle (small arrowhead).

Figure 4-42 A 67-year-old man with a diagnosis of oropharyngeal squamous cell carcinoma, referred for FDG PET/CT study performed with
contrast-enhanced high-resolution CT study for evaluation of extent of disease. Axial images of PET/CT study performed with contrast-enhanced
CT demonstrate increased FDG uptake (SUVmax 16.5) mainly in the right tongue with extension cranially to the palate, evident on the soft tissue
windows (second image from the left; small arrows). On the bone windows, the tumor abuts the right maxillary tuberosity, although there is
no definite evidence of bone destruction or erosion (first image from the left; arrowheads). Subsequent partial maxillectomy specimen revealed
no evidence of bone invasion. This finding probably is due to scattered photons from a highly FDG avid primary tumor that is situated in close
proximity to the maxillary bone.
166 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-43 A 57-year-old woman recently diagnosed with base of tongue squamous cell carcinoma (same patient as shown in Figure 4-10).
A: There is a large area of increased FDG uptake (SUVmax 14.8) involving the base of tongue extending into the supraglottic larynx (arrowheads)
(T2N1). B: On axial images of the chest of the whole-body PET/CT study, there is increased FDG uptake (SUVmax 6.5) in a left upper lobe pulmo-
nary nodule (small arrows), consistent with distant metastasis (T2N1M1).

Appropriate preoperative assessment using a com- those with oral cavity SCC for the development of dis-
bination of clinical and imaging studies may enhance tant metastases. Although more research is necessary to
the accuracy in detection of bone involvement. It may establish the superiority of PET over CT, currently FDG
be sensible to adopt a strategy of using FDG PET when PET appears to be a better imaging modality in identify-
there is a need to increase confidence and to better ing distant metastasis, with sensitivity and specificity of
define the extent of the primary tumor with respect to 80% to 95% and 85% to 95%, respectively, in advanced
involvement of osseous structures. stage HNSCC.

DOES FDG PET/CT HAVE A WHAT ARE THE COMMON

PRIMARY ROLE IN EVALUATION SITES FOR SYNCHRONOUS
OF DISTANT METASTASES? MALIGNANCIES?
Early detection of metastatic disease is critical due to Synchronous tumors can occur in the head and neck
prognostic and management implications. Nonethe- itself, lung, or upper aerodigestive tract, likely due to
less, distant metastases from HNSCC are rare at pre- shared risk factors. The reported prevalence of synchro-
sentation, with an overall incidence of less than 15%, nous or metastatic chest malignancy in patients with
whereas patients with locoregionally advanced tumors HNSCC varies from 2% to 37.5%, with a significantly
may be at higher risk for distant metastasis. The lungs higher prevalence in patients with recurrent disease
are the most common site of distant metastases (Figure compared to those at initial staging. In general, patients
4-43), followed by bone (Figure 4-44) and abdomen. with HNSCC have a 10% risk of developing a second
Mediastinal lymph node metastases are considered dis- aerodigestive tract primary malignancy. This number
tant metastatic disease (Figure 4-45). Patients with oro- is slightly higher at 15% for tonsillar and base of the
pharyngeal and laryngeal SCC are at higher risk than are tongue cancers. Patients with N2 or N3 neck disease
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 167

SECTION I
Figure 4-44 A 79-year-old man with a diagnosis of tongue squamous cell carcinoma, referred for FDG PET/CT study performed with contrast-
enhanced high-resolution CT study for evaluation of extent of disease. A: Axial images of the head and neck portion of the PET/CT study dem-
onstrate increased FDG uptake (SUVmax 15.3) corresponding to a heterogeneously enhancing tongue mass crossing the midline, measuring 4.5
cm (T3) (arrowheads). There is no evidence of lymph node metastasis (T3N0). B: On axial images of the pelvis of the whole-body PET/CT study,
there is increased FDG uptake (SUVmax 8.6) corresponding to the left pubic symphysis displaying a lytic lesion with a soft tissue component (small
arrows), consistent with distant metastatic disease (M1), confirming stage IV disease.
168 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-45 A 88-year-old man recently diagnosed with transglottic squamous cell carcinoma (same patient as shown in Figure 4-23), referred
for staging with FDG PET/CT performed with noncontrast-enhanced low-dose CT. A: Axial images of PET/CT study demonstrate a large hyper-
metabolic (SUVmax 14.8) predominantly supraglottic tumor with vocal cord fixation (determined by laryngoscopy) (T3) (arrowheads). B: On axial
images of the chest of the whole-body PET/CT study, there is increased FDG uptake (SUVmax 5.6) corresponding to a subcarinal lymph node (small
arrows). Subsequent biopsy revealed metastatic disease (M1), stage IV disease. The 1.0-cm mildly hypermetabolic right level III lymph node shown
in Figure 4-23 was not biopsied (NX). However, following chemoradiation, uptake has resolved (not shown). Thus, the presence of metastatic
disease in this lymph node could not be proven but in a stage IV setting would not change clinical management.

are more likely to have synchronous or metastatic chest in Surveillance of HNSCC After Therapy? for further
malignancy that are those with stage III or stage IV dis- discussion).
ease, and these indices could be used to select high-risk
patients. DOES FDG PET CHANGE
MANAGEMENT AT INITIAL
Is FDG PET Useful in Detecting STAGING?
Synchronous or Metachronous
FDG PET/CT yields additional information lead-
Malignancies?
ing to upstaging in 30% to 40% (Figures 4-11, 4-12,
The sensitivity of PET/CT is higher (96%–100%) than 4-24, 4-27, 4-32, 4-43, and 4-45) and thereby can
chest CT in identifying chest malignancy, but its speci- alter management in approximately 30% of patients.
ficity does not exceed 80%. The risk for development According to a physician survey study, FDG PET
of metachronous cancers increases with time after changed primary surgical plans to neoadjuvant ther-
completion of primary treatment of oral cavity and apy followed by surgery in approximately 20% and
laryngeal cancers (Figure 4-46). The role FDG PET in eliminated neoadjuvant therapy in approximately
detecting synchronous malignancies has not been fully 10% of patients. In addition, surgical plans were
investigated due to the relatively low risk for develop- modified in greater than 50% of patients based on
ing subsequent second malignancies in this group of FDG PET findings. The better definition of N staging
patients. Nonetheless, it may be appropriate to use using FDG PET/CT versus anatomic imaging led to
FDG PET in a surveillance setting for selected high-risk modification of radiotherapy volume and dose in at
groups (see the section, Does FDG PET/CT Have a Role least 30% of cases.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 169

SECTION I
A

B
Figure 4-46 A 57-year-old man with a history of base of tongue squamous cell carcinoma, status post primary therapy and right neck dis-
section, referred for evaluation of disease status 12 months after therapy performed with FDG PET/CT performed with contrast-enhanced high-
resolution CT study. A: Axial images of the head and neck portion of the PET/CT study demonstrate no evidence of recurrence. B: On axial images
of the chest of the whole-body PET/CT study, there is increased uptake (SUVmax 9.5) corresponding to the mid to distal esophagus (arrowheads),
which was subsequently proven to be a metachronous cancer in the esophagus of squamous cell origin.

DOES FDG PET HAVE A ROLE similar to that of CT at approximately 85%. In a meta-
IN IDENTIFYING PRIMARY DISEASE analysis, the pooled sensitivity and specificity of FDG
IN PATIENTS WITH CARCINOMA PET/CT were 37% and 84%, respectively. Lung and
OF UNKNOWN PRIMARY? oropharyngeal carcinomas were the most frequently
detected primary tumors by FDG PET/CT (33% and
Cervical metastases from an occult primary (carci- 16%, respectively). The most common locations of
noma of unknown primary [CUP]) constitute 5% to false-positive PET/CT findings are the lung and the oro-
10% of all HNSCC patients. Histologic categoriza- pharynx due to nonspecific uptake in granulomatous
tion of the CUP is important to allow for site-specific lung nodules and oropharyngeal and nasopharyn-
therapy, which offers better survival than a generic geal lymphoid tissues. The asymmetric nature of FDG
therapeutic approach. The majority of these cases uptake noted in the tonsillar fossa in some patients
are unresolved with respect to the primary pathology does not seem to increase test sensitivity because it can
despite vigorous workup and multiple directed biop- be seen as a normal variant or due to tonsillitis (Figure
sies. Generally, lymph node metastases from CUP in 4-15).
the levels I to III and V are associated with primary Despite its marginally better results in detecting the
HNSCC, particularly of tonsil origin (Figures 4-29 primary site (usually in 30%–40% of cases), FDG PET
and 4-30), whereas level IV involvement is linked to imaging still is associated with a higher number of
primaries of the chest and less frequently the abdo- false–negative results in the detection of CUP. Because
men or pelvis. a normal FDG PET result does not eliminate the need
Compared with conventional imaging, FDG PET for panendoscopy with multiple biopsies and tonsil-
provides a twofold higher sensitivity, with absolute val- lectomy in the case of CUP, it should be considered a
ues usually ranging between 22% and 87% depending supplemental test to conventional methods for achiev-
on the patient population. However, the specificity is ing the best possible yield.
170 Section I Advanced Modalities: Protocols and Optimization

IS THERE A ROLE FOR FDG PET/CT dissection. However, it is conceivable that a combina-
IN ASSESSMENT OF TREATMENT torial approach including clinical assessment, CT, and
RESPONSE? FDG PET imaging may yield the highest predictive
value. For example, in one study, combining PET and
Sufficient evidence now indicates that FDG PET imaging is CT results increased the specificity to 91%, which was
valuable in the assessment of response to therapy if timed approximately 10% higher than that of each test alone,
properly. Significantly decreased FDG accumulation after at no cost to the NPV of 94%.
chemoradiotherapy is associated with favorable tumor
response, survival, and local control. Conversely, persis- Does FDG PET Predict Response
tent FDG uptake indicates incomplete response and poor
in Primary Tumor?
outcomes. This topic is discussed for the primary tumor
and nodal disease separately in the following sections. In the detection of persistent disease at the primary site,
similar to nodal response evaluation, the timing of post-
What Is the Best Timing treatment FDG PET is particularly critical after radiation
for Evaluation of Response therapy. The most optimal timing for FDG PET is suggested
to Therapy? to be 2 to 3 months after completion of chemoradiother-
apy, yielding mean sensitivity, specificity, PPV, and NPV
The optimal timing of FDG PET/CT after radiation and of 90%, 70%, 30%, and 90%, respectively (Figures 4-48
chemotherapy is subject to ongoing debate due to the through 4-50). In addition to the false-positive results,
long-term persistence of posttreatment inflammatory management is challenged by false-negative results. This
changes. Radiation-induced inflammation can be con- is attributable to the fact that radiation therapy (RT) may
siderable within the first 2 months after treatment and hamper the FDG uptake mechanism early after therapy,
can last up to 18 months (Figure 4-47). If imaged very leading to inability of the tumor to accumulate FDG.
early after treatment, however, both false-positive and Although the accuracy of PET/CT is superior to that of
false-negative results equally challenge proper manage- ceCT in the neck, it appears to be equivalent at the pri-
ment. The majority of studies found that FDG PET/CT mary site in predicting persistent disease due to false-pos-
yields the highest negative predictive value (NPV) when itive results associated with PET readings (82% vs 86%).
performed 8 to 12 weeks after completion of radia-
tion therapy (~95%). Imaging performed more than 1 DOES FDG PET/CT HAVE A
month after completion of radiation therapy was found PRIMARY ROLE IN DETECTION
to have a significantly higher sensitivity compared with OF RECURRENT HNSCC DURING
PET scans performed within 1 month (95% vs 55%).
FOLLOW-UP AFTER THERAPY?
Does FDG PET/CT Predict Response The high risk of recurrence or the development of sec-
in Cervical Lymph Nodes? Does It ond primary malignancies warrants close follow-up of
Have a Primary Role in Deferring HNSCC patients after definitive therapy. Two thirds of
Planned Neck Dissection of HNSCC locoregional and metastatic recurrences occur in the
in the Posttherapy Setting? initial 2-year time period. Once the absence of residual
disease is established, continued surveillance with clini-
Following neoadjuvant therapy, identification of post- cal examination and imaging is pursued, especially in
therapy residual disease in cervical lymph nodes poses a the first 2 years of completion of treatment. Persistent
clinical challenge in patients with N2 to N3 disease. In or increased radiotracer uptake in the region of the
this group of patients, planned posttreatment neck dis- treated tumor may indicate residual or recurrent disease,
section is advocated; however, this aggressive approach especially if a mass is also detected on the correspond-
may not be indicated in all patients. ing CT section (Figure 4-51). Nonetheless, appreciation
After neoadjuvant chemoradiotherapy, the median of an accompanying mass on CT can be hampered by
sensitivity, specificity, and NPV for FDG PET imaging were posttherapy changes (Figure 4-52). For the detection of
reported to be 73%, 83%, and 92%, respectively (Figures locoregional recurrence, FDG PET has a higher specificity
4-15, C, 4-30, and 4-48 through 4-50). Negative PET results (~90%) and NPV (>95%) than sensitivity (~80%) and
are highly reliable in excluding the possibility of residual PPV (64%) owing to false-positive findings (Figures 4-53
nodal disease with negligible false–negative results. How- and 4-54). For detection of distant metastases during
ever, FDG PET results can be false positive in at least one follow-up, PET has a higher sensitivity (~90%) and PPV
third of these patients. In addition, several studies have (85%) and equal specificity (>95%) and NPV (>95%)
reported unfavorable results for FDG PET imaging, reveal- compared to detection of locoregional recurrence.
ing a false-negative rate as high as 20%. Nonetheless,
PET-based assessment changes the response category in What Are the Characteristics
approximately 30% of patients, mostly by upgrading par- of Recurrent Disease in Oral
tial response based on conventional assessment alone to
and Oropharyngeal Cancers?
a complete response (Figures 4-15, C, 4-30, B, and 4-48).
In summary, FDG PET currently has not been fully The pattern of recurrence in oral cavity SCC differs from
validated to have the capability to guide the surgeon in that of oropharyngeal SCC in the higher rate of nodal
deciding whether or not to perform or withhold neck and distant metastases seen in the latter disease entity.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 171

SECTION I
3 mo

12 mo

18 mo

C
Figure 4-47 A 68-year-old man with a history of left base of tongue squamous cell carcinoma, status post primary therapy with chemoradia-
tion, referred for evaluation of disease status with FDG PET/CT with low-dose CT, 3, 12, and 18 months after completion of therapy. A: Three-
month PET/CT study demonstrated increased uptake in the left base of tongue (arrowheads), most consistent with postradiation changes. However,
residual tumor cannot be definitively excluded. Uptake gradually decreased over time at 12-month (B) and 18-month (C) PET/CT studies (arrow-
heads), consistent with gradual regression of inflammation induced by radiation therapy.
172 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-48 A 59-year-old man with recent diagnosis of right base of tongue squamous cell carcinoma. A: Pretherapy PET/CT study performed
with noncontrast-enhanced low-dose CT demonstrates increased FDG uptake (SUVmax 19) in the right base of tongue (arrowheads), consistent
with the patient’s known primary tumor. There is increased uptake (SUVmax 14.5) in an enlarged right level II lymph node (arrows), consistent with
metastatic disease. B: The patient subsequently underwent neoadjuvant therapy with chemoradiation and was referred for evaluation of therapy
response 11 weeks after completion of therapy. There is complete resolution of uptake in the right base of tongue and in the right level II lymph
node station despite the presence of a residual soft tissue density in the neck (arrows), consistent with complete response to therapy. The mild
uptake noted in the oropharyngeal wall bilaterally probably represents normal lymphoid tissue (small arrowheads).
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 173

SECTION I
A

B
Figure 4-49 A 49-year-old man with recent diagnosis of right supraglottic squamous cell carcinoma. A: Pretherapy PET/CT study performed
with low-dose CT demonstrates increased FDG uptake (SUVmax 11) in a large right supraglottic soft tissue mass, consistent with the primary tumor
(arrowheads). The right preglottic space is obliterated. B: The patient underwent neoadjuvant therapy with chemoradiation and was referred for
evaluation of therapy response 11 weeks after completion of therapy. There is resolution of uptake in the supraglottic region with mild residual
uptake (SUVmax 1.8) (arrows). Although minimal residual disease cannot be ruled out, the pattern of uptake is diffuse and also is confined to the
luminal/mucosal aspect of the larynx. Thus, this finding is most consistent with postradiation inflammatory changes in the epithelial surfaces.
This finding persisted on the following 3-month PET/CT study, warranting a biopsy that revealed squamous cell proliferation with no evidence
of malignancy.
174 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-50 A 59-year-old woman who presented with a tonsillar squamous cell carcinoma. A: Pretherapy PET/CT study performed with low-
dose CT demonstrates increased FDG uptake (SUVmax 13.6) corresponding to a soft tissue mass involving the right palatine tonsil (arrowheads),
consistent with the patient’s primary tumor. The patient subsequently underwent neoadjuvant therapy with chemoradiation. B: Posttherapy FDG
PET study performed 4 months after completion of chemoradiation therapy demonstrates no area of abnormal FDG uptake in the corresponding
region, consistent with complete response to therapy. Note minimal uptake in the prevertebral (longus colli) muscles (small arrows) probably as
a result of tension.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 175

SECTION I
A

B
Figure 4-51 A 66-year-old man with a history of stage III left base of tongue squamous cell carcinoma. A: Posttherapy PET/CT study performed
with low-dose CT 4 months following primary therapy demonstrates postsurgical changes, including architectural distortion in the left neck but
no area of abnormal FDG uptake except for mild uptake (SUVmax 4.1) in the left base of tongue (arrowheads) with minimal extension to the mid-
line, which can be attributable to lymphoid tissue. Subsequent biopsy of this region revealed hyperplastic squamous mucosa with no evidence
of tumor recurrence. Because the patient’s primary tumor was in the left base of tongue, close follow-up was indicated. B: Three-month follow-
up PET/CT study performed with contrast-enhanced CT demonstrates a distinct focus of increased FDG uptake (SUVmax 6.9) in the left base of
tongue, medial to the mylohyoid muscle in the posterior aspect of the genioglossus muscle, where an ill-defined mildly enhancing mass is noted
(arrows) on the accompanying CT study, most consistent with recurrent tumor. Subsequent biopsy revealed malignant squamous cells. If FDG PET
was not performed, contrast-enhanced CT alone would prove equivocal, and the diagnosis of recurrence would have been delayed. The patient
subsequently underwent salvage surgery after biopsy confirmation of the recurrence.
176 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-52 A 59-year-old man with a history of tongue squamous cell carcinoma. A: Posttherapy PET/CT study performed with low-dose
CT 6 months after primary therapy demonstrates no area of abnormal FDG uptake. B: Three-month follow-up PET/CT study performed with
contrast-enhanced high-resolution CT demonstrates distinct foci of increased FDG uptake (SUVmax 7.6) in the left lateral surface of the tongue
(small arrows) and oropharyngeal wall (right arrows) associated with a nonenhancing mass on the accompanying CT study, consistent with recur-
rent tumor. Subsequent biopsy confirmed recurrence. In this case, both PET and CT complement each other, increasing the certainty of diagnosis
of recurrent disease. The patient underwent salvage surgery and has been alive until the last follow-up visit in 2010.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 177

SECTION I
A

C
178 Section I Advanced Modalities: Protocols and Optimization

Figure 4-53 A 78-year-old man with a history of tongue squamous cell carcinoma, status post primary treatment with chemoradiation fol-
lowed by partial glossectomy involving bilateral neck dissection. PET/CT studies performed, 6 months (A), with contrast-enhanced high-resolu-
tion CT, 12 months with low-dose CT (B), and 18 months with contrast-enhanced high-resolution CT (C) after completion of primary therapy
demonstrate significantly increased uptake [SUVmax range 9 (A) to 26 (C)] corresponding to the tongue with either partial (A and B) or diffuse
involvement of the tongue (C; arrows). Although these findings can be easily interpreted in favor of recurrent disease, in the absence of a dominant
mass noted on the accompanying contrast-enhanced CT, this is rather unlikely. In this patient, subsequent biopsy at the central tongue revealed
only skeletal muscles and fibroadipose tissue. Note that this pattern of uptake is frequently seen in patients with partial glossectomy and can be
attributable to constant use of unusual muscle groups activated after surgery leading to significant physiologic uptake by these otherwise unused
muscle groups.

B
Figure 4-54 A 62-year-old man with a history of right neck carcinoma of unknown origin, status post right selective neck dissection and diag-
nostic laryngoscopy. A: Six-month posttherapy PET/CT study performed with contrast-enhanced high-resolution CT shows surgical clips in the
right neck with no evidence of recurrence. B: Nine-month follow-up PET/CT study performed with contrast-enhanced CT demonstrates interval
appearance of increased uptake (SUVmax 3.6) in left-sided level IB (small arrows) and level IIA lymph nodes (large arrows) measuring up to 1.3
mm (previously measured 6 mm). Note that these lymph nodes demonstrate a fatty hilum, smooth margins, and no pathologic enlargement.
Although recurrence cannot be excluded, in the absence of obvious pathologic findings on the accompanying CT, reactive changes should be
considered first. Subsequent fine needle aspiration (FNA) biopsy of one of these lymph nodes revealed no evidence of malignancy.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 179

SECTION I
A

B
Figure 4-55 A 57-year-old man with right base of tongue squamous cell carcinoma, status post pharyngectomy, base of tongue resection, and
radiation therapy. A: Eighteen-month follow-up PET/CT study performed with contrast-enhanced high-resolution CT demonstrates an area of
increased FDG uptake (SUVmax 12) in the right base of tongue corresponding to a hypodense lesion (arrows). There is also increased FDG uptake
in the anterior right floor of mouth, corresponding to an ill-defined soft tissue density (arrowheads), consistent with a second focus of recurrent
tumor. B: On axial images of the abdomen/pelvis of the whole-body PET/CT study, there is increased FDG uptake (SUVmax 11.5) in the right aspect
of the L4 vertebral body (arrows), associated with no obvious pathology seen on CT study. These findings are consistent with distant metastasis,
which is common in patients who have precipitous disease course and high disease burden at recurrence.

Posttreatment follow-up usually focuses on detection of a­ ssociated with masses with or without enhancement
locoregional recurrences, which dominate the clinical (Figure 4-56). Abnormalities at the margin of a previous
presentations following primary therapy (Figures 4-51 resection or reconstruction are difficult to detect without
and 4-52). Distant metastatic disease is not commonly a FDG PET study due to altered anatomic planes and the
observed except in patients who have not responded to presence of metallic artifacts (Figure 4-57). One special
multiple therapies or have high disease burden at recur- concern following radiation therapy is the increased risk
rence (Figure 4-55). FDG PET/CT features that indi- for developing osteoradionecrosis or cartilage necro-
cate locally recurrent disease include increased uptake sis which accumulate significant amounts of FDG.
180 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-56 A 76-year-old man with left base of tongue squamous cell carcinoma, status post base of tongue resection, left neck dissection,
and radiation therapy four months ago. A: PET/CT study performed with contrast-enhanced high-resolution CT demonstrates a vague area of
increased FDG uptake (SUVmax 3.8) in the left base of tongue (arrows) in the vicinity of a surgical clip with no association of a mass noted on the
accompanying CT study. B: Four months later, repeat PET/CT with contrast-enhanced CT shows significant interval increase in FDG uptake in the
corresponding region (SUVmax 14.5), now associated with an enhancing mass (arrows), consistent with recurrent tumor, which was proven by a
subsequent biopsy. Note the stable FDG uptake at the midline base of tongue near the vallecula seen in both A and B (small arrowheads), consistent
with lymphoid tissue.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 181

SECTION I
A

B
Figure 4-57 A 90-year-old man with a history of tongue squamous cell carcinoma (SCC), status post glossectomy and left neck dissection.
A: Nine-month follow-up PET/CT study with contrast-enhanced high-resolution CT demonstrates multiple surgical clips in the left supraclavicular
region with no definite evidence of pathologically increased FDG uptake. There was no abnormal FDG uptake in the tongue and adjacent struc-
tures at this time (not shown) in the tongue or the neck. B: Twelve-month follow-up PET/CT with contrast-enhanced CT shows interval appear-
ance of an area of increased uptake in the left supraclavicular region near the surgical clips (arrows). Although evaluation with CT is limited due
to metallic artifacts, a vaguely enhancing soft tissue mass can be seen on the corresponding CT study (arrows). These findings are consistent with
recurrent tumor. Subsequent biopsy of this lesion revealed poorly differentiated SCC.
182 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-58 A 77-year-old man with laryngeal squamous cell carcinoma, status post radiation therapy. A: Six-month follow-up PET/CT study
with high-resolution CT but no contrast administration demonstrates increased FDG uptake (SUVmax 9.2) in the posterior aspect of the right thy-
roid cartilage, adjacent to the piriform sinus (arrows). The cartilage displays sclerotic changes. Although a malignant process cannot be ruled out,
the location of this finding is more consistent with chondronecrosis. B: Nine-month follow-up PET/CT with contrast-enhanced CT shows slight
progressive sclerosis of the posterior edge of the right thyroid cartilage with focal increased FDG uptake (SUVmax 7.0). Areas of lack of ossification
have progressed compared to the earlier area of increased uptake (arrows). Biopsy revealed benign portion of larynx with ossified thyroid cartilage
showing degenerative changes. The patient gradually developed a nonfunctional larynx with aspiration and weight loss and ultimately underwent
total laryngectomy. The surgical specimen revealed chondronecrosis with acute and chronic inflammation.

Thus, differentiation from recurrent tumor usually is dif- have positive margins after surgical resection and extra-
ficult with all imaging modalities including FDG PET/CT capsular extension of disease in cervical lymph nodes,
(Figures 4-58 and 4-59) (see the section, What Are the or have multiplicity of involved lymph nodes that con-
Pitfalls in Evaluation of HNSCC? For further discussion). stitute high-risk categories for tumor recurrence. Laryn-
goscopy with general anesthesia is routinely performed
What Are the Characteristics of in patients suspected of having residual or recurrent
Recurrent Disease in Laryngeal disease; however, laryngeal edema negatively affects the
performance of this test. In this circumstance, FDG PET/
Cancers?
CT performs better than ceCT in identifying the presence
The sensitivity of FDG PET in the detection of recurrence of residual disease (Figures 4-60 and 4-61). However,
is significantly high, but its specificity can be as low as in the postsurgical period, particularly in the vicinity
65% due to varying degrees of inflammatory processes. of the tracheostomy site, the specificity of FDG find-
Patients whose primary tumors manifest deep invasion ings can be marred by FDG uptake due to the chronic
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 183

SECTION I
Figure 4-59 A 79-year-old woman with a history of tongue squamous cell carcinoma, status post radiation therapy, partial glossectomy, and
bilateral neck dissection. Nine-month follow-up PET/CT study performed with contrast-enhanced high-resolution CT demonstrates significantly
increased uptake (SUVmax e 9.5) corresponding to the left mandible, displaying destructive changes (arrows). Although these findings can be
interpreted as favoring recurrent disease with involvement of the bone, osteoradionecrosis should be a strong consideration, particularly in the
absence of a soft tissue density (soft tissue windows not shown). Subsequent partial mandibular resection revealed osteonecrosis with no evidence
of tumor. Note diffuse uptake in the residual viable tongue (diagonal arrows) and right mylohyoid muscle, not well shown without the soft tissue
windows (arrowheads). Subsequent biopsy at the central tongue revealed no evidence of a malignant process. This pattern of uptake can be attribut-
able to constant use of unusual muscle groups activated after surgery.

B
Figure 4-60 A 65-year-old woman with left base of tongue/tonsil squamous cell carcinoma, with local recurrence 9 years after primary defini-
tive chemoradiation, treated with composite resection, total laryngectomy, and left selective node dissection. A: Three-month follow-up PET/CT
study with contrast-enhanced high-resolution CT demonstrates mildly increased FDG uptake (SUVmax 4.7) in the anterior aspect of the trachea, in
the midline. Accompanying CT demonstrates no obvious abnormality; however, there is suggestion of an enhancing nodule situated subcutane-
ously at the corresponding site (arrows). These findings may represent postsurgical inflammatory changes; however, the focal nature of FDG uptake
corresponding to an enhancing mass seen in the right ill-defined soft tissue nodule raises suspicion for recurrent/residual disease. B: Six-month
follow-up PET/CT with contrast-enhanced CT shows interval increase in size and metabolic activity (SUVmax 18.4) within the aforementioned soft
tissue mass in the right subglottic region anteriorly, extending through the lateral margin of the laryngeal cartilage and lies in close proximity to
surgical clips within the right neck (arrows), consistent with extensive tumor recurrence.
184 Section I Advanced Modalities: Protocols and Optimization

Figure 4-61 A 64-year-old man with a history of recurrent transglottic squamous cell carcinoma (SCC), status post total laryngectomy with
creation of neopharynx. Four-month follow-up PET/CT study with contrast-enhanced high-resolution CT demonstrates focally increased FDG
uptake (SUVmax 7.7) corresponding to an area associated with a surgical clip and thickening of the neopharynx/esophagus superiorly (arrows).
Although no separate discrete mass is appreciated in this region, the focal and intense nature of FDG uptake is most consistent with tumor recur-
rence/residual tumor. In addition, evaluation of the CT study is limited by metallic artifacts obscuring the region for the presence of an associated
soft tissue. Subsequent endoscopic biopsy revealed recurrent poorly differentiated SCC, and the patient was started on chemotherapy.

i­ nflammatory changes usually induced by repeat manip- What Is the Optimal Timing for
ulations (Figure 4-62). Patients can also present with Sequential Evaluation in Detection
recurrent disease outside the head and neck because of Recurrent Disease?
chemoradiation followed by surgery is effective in local
control but cannot prevent distant metastasis (Figure In general, the 5-year risk for both locoregional recur-
4-63). In a retrospective study, Gourin et al found that rence (30%–50%) and distant metastases (20%–30%)
the incidence of distant metastases in patients with sus- for patients with head and neck SCC is fairly high.
pected recurrent disease was approximately 25%, with Patients with HNSCC should be followed closely both
sensitivity and specificity of FDG PET/CT of 86% and clinically and radiographically for the first 2 years after
84%, respectively. treatment because most recurrences present within this
period. However, debate still exists over the optimal tim-
DOES FDG PET/CT HAVE A ROLE ing of the first surveillance imaging study. Early PET/CT
IN SURVEILLANCE OF HNSCC imaging within 1 month of therapy yields low sensitiv-
ity due to the paucity of viable tumor cells as well as the
AFTER THERAPY?
presence of transient fluctuations in FDG uptake early
One controversial issue is the application of FDG PET/ after treatment. Specificity is also negatively impacted
CT in a surveillance setting. Conceivably, a survival during the early posttreatment period secondary to ther-
benefit can be achieved for patients who have an early apy-induced inflammatory changes (Figures 4-49, B,
asymptomatic recurrence following primary therapy. 4-68, and 4-69). PET scans performed 3 months after
Goodwin et al reported that patients with recurrent, completion of therapy have high sensitivity exceeding
early-stage HNSCC who undergo salvage surgery have 82% and specificity close to 90%. The majority of PET
a 70% 2-year relapse-free survival, whereas those with negative cases recur after median follow-up of more than
recurrent, advanced-stage HNSCC undergoing surgical 12 months (Figures 4-64 through 4-67). It is acceptable
salvage have just a 22% 2-year relapse-free survival. to adopt a follow-up policy of ceCT 1 month after defin-
Hence, early detection of recurrent HNSCC is criti- itive therapy, then FDG PET/ceCT every 3 months for
cally important for achieving a successful surgical sal- the first year, then every 6 months for the second year,
vage. Second primary malignancies can also be detected and annually thereafter for 5 years or until recurrence
early by frequent follow-up. Early recurrence in HNSCC (Figures 4-51, 4-54, 4-56, 4-57, 4-60, 4-62, and 4-64).
may be asymptomatic in nearly 50% of patients, and Patients with scans highly suggestive of recurrence
FDG PET/CT may improve early detection of recur- should undergo tissue confirmation, whereas patients
rence (Figures 4-64 through 4-67). A systematic review with questionably abnormal findings should undergo
revealed that the pooled sensitivity, specificity, PPV, and additional PET/CT 3 months later. Posttherapy baseline
NPV of PET for detecting residual or recurrent HNSCC PET/CT should be performed 2 to 3 months after the
were 94%, 82%, 75%, and 95%, respectively. conclusion of therapy.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 185

SECTION I
A

B
Figure 4-62 A 55-year-old man status post chemoradiation for treatment of advanced laryngeal and hyperpharyngeal squamous cell carci-
noma. The patient had undergone attempted decannulation in the past but because of severe chronic granulation tissue and stenosis has been
tracheostomy dependent since 6 months ago. A: Six-month follow-up PET/CT study performed with contrast-enhanced high-resolution CT dem-
onstrates increased FDG uptake (SUVmax 5.2) in the left posterior aspect of the tracheostomy site (arrows). Accompanying CT study demonstrates
no obvious abnormality. However, significant metallic artifacts hamper the evaluation by CT. These findings may represent postsurgical inflamma-
tory changes. However, the focal nature of the FDG uptake prompted close follow-up. B: Nine-month follow-up PET/CT with contrast-enhanced
CT shows persistently increased FDG uptake near the tracheostomy site (arrows), somewhat more prominent and extensive compared to the prior
study (SUVmax 6.4). Again, the findings on the accompanying CT are hampered by metallic artifacts. A recurrent tumor could not be ruled out
because these findings are nonspecific for both recurrence and inflammatory changes. Subsequent biopsy revealed granulomatous changes with
acute and chronic infection. False-positive FDG PET findings are common in the presence of significant inflammation.

B
Figure 4-63 A 57-year-old man with tonsillar squamous cell carcinoma, status post pharyngectomy, partial base of tongue resection, and
radiation therapy. A: Fifteen-month follow-up PET/CT study with low-dose CT demonstrates increased FDG uptake (SUVmax 9.5) corresponding
to a large hypodense mass in the dome of the liver (arrows) new since the prior study (not shown), consistent with hepatic metastasis. B: There is
a large lytic lesion with significant FDG uptake (SUVmax 17) in the right acetabulum (arrows), consistent with distant osseous metastatic disease.
186 Section I Advanced Modalities: Protocols and Optimization

C
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 187

Figure 4-64 A 72-year-old man with a history of right base of tongue squamous cell carcinoma, status post base of tongue resection, right neck

SECTION I
dissection, and radiation therapy. A–C: Follow-up PET/CT studies performed with contrast-enhanced high-resolution CT at 3, 6, and 9 months,
respectively, demonstrate gradually increasing FDG uptake in the right level IIB region with no obvious CT abnormality except for a small lymph
node that shows normal morphology (arrows). Due to multiple surgical clips, evaluation of CT is suboptimal, and a dominant mass cannot be
appreciated even on the last follow-up PET/CT study when the SUVmax of the level IIB lesion reaches 11.5 (C) from 3.2 (B) on the prior study.
These findings are consistent with recurrent disease, which was proven by subsequent biopsy. Note the value of FDG PET study in identifying
recurrent disease preceding pathologic findings on CT.

B
Figure 4-65 A 66 year-old man with a history of right base of tongue squamous cell carcinoma, status post therapy with resection and right neck
dissection. A: Nine-month PET/CT study with low-dose CT demonstrates no abnormal finding except for diffuse uptake corresponding to surgical
clips (arrowheads) probably representing physiologic changes and/or muscle tension of tissue inflammation. B: Twelve-month follow-up PET/CT
study performed with contrast enhanced high-resolution CT reveals focal increased FDG uptake (SUVmax 4.3) near the clips but now corresponds
to a subtle soft tissue nodule (arrows), which is highly suspicious for recurrent disease. Subsequent biopsy confirmed recurrence, and the patient
underwent salvage therapy. Early recurrence in squamous cell carcinoma of the head and neck may be asymptomatic in nearly 50% of patients,
and FDG PET/CT may improve early detection of recurrence.
188 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-66 A 69-year-old man with a history of recurrent tongue squamous cell carcinoma, status post hemiglossectomy A: Six-month follow-
up PET/CT study performed with contrast-enhanced high-resolution CT demonstrates diffusely increased symmetric FDG uptake in the oral cavity
with no focal uptake, probably representing postsurgical changes. Note tissue heterogeneity on the right side of the oral cavity that represents
surgical changes (arrowheads). B: Twelve-month follow-up PET/CT study performed with contrast-enhanced high-resolution CT demonstrates
increased FDG uptake (SUVmax 11) in the region of the right tongue along the previously resected tongue (arrows), corresponding to a streaky and
slightly enhancing soft tissue density, consistent with recurrent tumor. Subsequent biopsy of this region confirmed recurrent tumor.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 189

SECTION I
A

B
Figure 4-67 A 72-year-old woman with a history of tongue squamous cell carcinoma, status post partial glossectomy, left selective lymph node
dissection, and flap reconstruction. A: Six-month follow-up PET/CT study with contrast-enhanced CT demonstrates no abnormal increased FDG
uptake in the head and neck region. B: Nine-month follow-up PET/CT study with contrast-enhanced CT demonstrates interval development of
two discrete foci of radiotracer uptake (SUVmax 13.4) in the left posterior lateral neck in the level IIB region associated with increased soft tissue
density (small and large arrows), likely representing metastatic lymph nodes. Artifacts from the clips limit evaluation of the soft tissues of the left
neck and tongue. Note the value of FDG PET imaging in the identification of recurrent disease and the development of recurrence within a rather
short interval, which would require frequent follow-up PET/CT imaging to detect recurrence at an earlier period than by conventional methods.
190 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-68 A 50-year-old man with a history of left hard palate squamous cell carcinoma, status post resection and reconstruction with free
flap. A: Six-month follow-up PET/CT study with contrast-enhanced high-resolution CT demonstrates mildly increased FDG uptake (SUVmax 3.5)
in the posterior margin of the surgical bed corresponding to mild soft tissue thickening at the resection margin and along the posterior left maxil-
lary and palatal walls (arrowheads). There is also asymmetric uptake (SUVmax 3.0) in the right nasopharyngeal wall with no soft tissue abnormality
(arrows). These findings probably represent postsurgical changes. However, recurrent disease cannot be excluded. Note the opacification in the left
maxillary sinus (small arrowheads). Subsequent biopsy revealed inflammatory changes. B: Nine-month follow-up PET/CT with contrast-enhanced
CT demonstrates resolution of uptake in the palate with persistence of opacification in the left maxillary sinus, consistent with resolution of the
inflammatory change. Note the interval decrease in FDG uptake in the right nasopharyngeal wall, which probably represents asymmetric lym-
phoid tissue secondary to treatment changes on the contralateral site (arrows) and resolution of previous lymphoid hyperplasia, which might be
due to ongoing inflammation in the palate.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 191

SECTION I
Figure 4-69 A 67-year-old man with a history of left vocal cord squamous cell carcinoma, status post laser excision. Four-month follow-up
PET/CT study performed with low-dose CT (low-dose CT slice not shown) and separately acquired contrast-enhanced high-resolution CT dem-
onstrate increased FDG uptake (SUVmax 2.2) in the anterior commissure of the larynx, probably representing posttherapy inflammatory changes,
particularly, in the absence of a soft tissue density on the accompanying CT study. Subsequent laryngoscopic examination was unremarkable, and
the patient has been recurrence free for a follow-up period of 12 months. Note that the uptake localized in the anterior commissure in untreated
patients is almost invariably associated with malignant causes, however, in the posttherapy setting, inflammatory changes may also occur in this
region (compare with Figure 4-78).

Local recurrence rates for laryngeal SCC can be sub- discrete or dominant mass on CT slices. These changes
stantially high, ranging from 15% to 50%. Recurrence should decrease with time, so follow-up scans usually
of advanced compared to early-stage laryngeal carci- increase test specificity. It is preferable to wait 10 to 12
nomas is approximately twice as high (10%–25% vs weeks after completion of treatment before perform-
25%–50%). Once recurrence occurs, treatment options ing imaging to reduce false-positive results, particularly
are dictated by the mode of treatment previously given, after radiation therapy (RT).
tumor volume of recurrent disease, and performance
status and comorbidities of the patient. The gold stan- What are the Surgically Induced
dard for diagnosing recurrent laryngeal tumor is direct
Changes in the Head and Neck?
laryngoscopy. However, laryngoscopy is invasive and is
not conducive to evaluation of lymph nodes or distant Postsurgical changes can result in various degrees of
metastases. A systematic review laryngeal carcinoma by FDG uptake ranging from subtle to avid accumulation
Brouwer et al revealed sensitivity of 89% and specific- depending on the procedure and the time between
ity of 74% for FDG PET in the detection of recurrent imaging and surgery (Figures 4-70 through 4-76).
tumor after radiotherapy. In a retrospective study of Interference from surgical metallic clips and recon-
78 patients by Martin et al revealed different results struction hardware are common during the postoperative
for sensitivity and specificity of 82% and 95%, respec- follow-up period. Although these artifacts usually do not
tively, in detecting residual disease after treatment with cause false-positive readings, in some cases FDG uptake can
chemoradiotherapy for mucosal carcinoma of the head be focal and prominent and can prove challenging to the
and neck. reader and surgeon alike with respect to subsequent man-
agement due to the inability to delineate a clear-cut soft
WHAT ARE THE PITFALLS tissue association on the CT portion of the study (Figure
4-70). Mandibular reconstructions using titanium mesh
IN EVALUATION OF HNSCC?
with bone and marrow harvested from the iliac bone are
Interpretation of the posttreatment neck can be chal- performed in a second stage and may present a high com-
lenging due to alterations in anatomic spaces and plications rate. Another source of false-positive findings
planes, development of postradiation inflammatory is dental interventions, which are frequent due to various
changes, and ensuing fibrosis. Surgical resection, flap therapeutic insults to the osseous structures in this patient
reconstruction, radiation, and frequent use of adjunc- population (Figure 4-71). In particular, dentures may
tive treatments naturally result in significant morpho- cause chronic trauma to the gum line, and the resulting
logic and inflammatory changes in the involved regions, periodontal disease and apical periodontitis demonstrate
including edema, inflammation, fibrosis, distortion of increased FDG uptake (Figure 4-72). Specific pitfalls in
anatomic planes, complex muscle activity resulting from posttreatment imaging of the larynx on FDG PET include
flaps, and loss of symmetry (Tables 4-2 through 4-4). mild homogeneous FDG uptake due to tissue healing at
As a principle, FDG uptake at inflammatory or ana- the tracheostomy site (Figure 4-73, A and B) and tracheo-
tomically altered sites should not be associated with a esophageal puncture for a placement of a voice valve.
192 Section I Advanced Modalities: Protocols and Optimization

Table 4-2 PET/CT Imaging Characteristics of Benign and Malignant Processes in Tumors of the Head and Neck
Common Anatomic
Location for FDG-
Organ PET findings Benign Malignant
LNs Levels I –V (levels I-IV Usually SUV<4.0* Usually SUV>4.0
most relevant) Morphology: higher short to long axis ratio Morphology: length close to its width (round),
(longer than wider), contains hilar fat, does not contain fat, may have necrotic or cystic
smooth borders, no stranding in the adjacent change, irregular or ill-defined margins, strand-
fat, may contain calcification ing or infiltrative changes in the adjacent fat, no
Attenuation or enhancement: usually calcification
uniform except in areas of fatty content, or Attenuation or enhancement: heterogeneous but
vascular flow voids but can give a heteroge- can be uniform as well
neous feature
Lymphoid Waldeyer’s ring No recommendation for SUV: hyperplastic Usually asymmetrical*
tissues lymphoid hyperplasia can present with SUVs Enhancing mass can be seen on the contrast-
as high as >10 enhanced CT
Usually symmetrical, no discrete mass is seen
Lingual tonsils may extend from base of
tongue to the anterior portion of the val-
leculae
Neck Muscles Longus colli, ptery- No recommendation for SUV: asymmetric Usually asymmetrical
goids, temporalis, use of unusual muscle groups can present Enhancing mass can be seen on the contrast-
masseter, extrinsic with SUVs as high as >10 enhanced CT
tongue sternocleido- Can be both symmetrical or asymmetrical,
mastoids, scalenes no discrete mass is seen
Larynx Supraglottic and glot- No recommendation for SUV: phonation Usually asymmetrical uptake
tic larynx during the injection and wait period can Anterior commissure uptake at initial staging
cause significant uptake in vocal cords is generally of malignant cause, however, after
asymmetric uptake can be seen in unilateral therapy low grade uptake can be attributable to
vocal cord paralysis treatment-related inflammatory changes (radia-
Can be symmetrical or asymmetrical, no tion therapy or laser surgery)
discrete mass is associated with asymmetrical Enhancing mass can be seen on the contrast-
uptake if contrast-enhanced CT is performed enhanced CT
Post therapy edema can accumulate mild
degree FDG uptake
Base of tongue lymphoid tissue can extend
to the level of vallecula
Salivary Parotid Can be symmetrical or asymmetrical, usually Focal asymmetrical FDG uptake associated with
glands submandibular no discrete mass is associated with symmet- a mass/masses, usually ill-defined and demon-
rical uptake on the contrast-enhanced CT strate infiltration into the surrounding tissues.
Can be focal and intense degree of uptake In the presence of enlarged and hypermetabolic
associated with a well-defined/discrete mass/ lymph nodes, the likelihood of malignancy
masses in the case of Warthin’s tumor, pleo- increases significantly
morphic adenoma or intraparotid reactive Invariable moderate to high grade FDG uptake
lymph nodes except in tumors of minor salivary gland origin
which can show low grade or no FDG uptake
Gumline Alveolar ridge sur- No FDG uptake should be seen in the Usually focal intense and associated with a
rounding the man- gumline. mass. The mass can be unnoticed if noncon-
dible and maxilla The diffuse pattern of uptake is usually due trast CT, thus contrast-enhanced CT should be
to periodontal disease or denture related obtained or available at the time of evaluation
inflammation, regardless of the degree of
uptake
Cartilage Laryngeal No FDG uptake should be seen. Focal or diffuse uptake at initial staging should
trachea raise suspicion for tumor involvement
Bones No FDG uptake should be seen except low Cortical invasion or destruction with FDG
grade diffuse uptake in the vertebral column uptake

*No consensus exists with respect to a SUV cut-off to define maligancy. SUV ≥ 4 has been our experience to favor malignancy through a vast number of cases,
although false positive results still occur.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 193

Table 4-3 B
 enign Conditions with Increased FDG Table 4-4 H
 ow to Avoid Misinterpretation at Initial

SECTION I
Uptake Staging?
Stage Assessment
• Warthin’s tumor
• Pleomorphic adenoma T staging Define metabolism/FDG uptake on PET study
• Inverted papilloma (Schnederian cyst) Define size and location of the primary lesion
• Active granulomas on associated CT
• Sinus infection Examine, margins in relation to adjacent organs
• Lymphoid hyperplasia (Waldeyer’s ring) on CT
• Postsurgical unilateral muscle uptake Look for
• Tongue uptake after glossectomy –surrounding tissue infiltration
• Fasciculation of grafts and other inflammatory graft-related – signs for invasion of cartilage, bone, adjacent
changes organs
• Postradiation or laser therapy inflammation – invasion of specific sites important for surgical
• Ostomies (e.g., tracheostomy, gastrostomy) eligibility
• Dental interventions
• Osteonecrosis N staging Define metabolism/FDG uptake on PET study
• Cartilage necrosis Define level of LNs
• Tracheostomy Define size, eccentricity, examine morphology
• Vocal cord paralysis of lymph nodes
Look for
– irregular borders and/or surrounding fat
infiltration
– calcifications, fat in the hila to rule in benign
Reconstructive procedures of the head and neck aim process
to repair soft tissue and bony defects while restoring – heterogeneity in attenuation to rule in
­malignant process
optimal function and cosmesis. Postresection defects – central necrosis to rule in malignant process
may require reconstruction with prostheses, musculocu- – evidence of coalescence
taneous-free flap, or pedicled flaps (Figure 4-74). These
M staging Look for focal FDG uptake in the
surgical changes may result in either focal or diffuse FDG and second – Remainder of the head and neck organs
accumulation in the involved muscle structures, so false primary – Lungs
interpretations are common in the posttherapy period. – Bones
Particularly in patients undergoing partial or total glos- – Esophagus
– Colon
sectomy with flap reconstruction, the extensive surgery, – Liver
altered anatomy, compromised functionality of the rem- – Other GIT organs
nant tongue, lack of mobility of the flap, and fascicula-
tions of the myocutaneous flaps can lead to asymmetric
use of muscles or activation of unusual muscle groups;
therefore, the physiologic FDG uptake patterns can be results. Necrosis of the cartilage and bone appears as
unpredictable (Figures 4-53 and 4-75). In the absence mixed sclerosis and lucency, sometimes with fragmen-
of a CT abnormality, increased FGD uptake should be tation, and can result in marked FDG uptake on PET
interpreted with caution despite high levels of uptake (Figure 4-59). In the case of osteoradionecrosis, it is dif-
(Figures 4-51 and 4-56). ficult to differentiate between persistent or aggravating
In patients with oral cavity and oropharyngeal bone necrosis and tumor recurrence (Figure 4-60). Inter-
tumors and composite mandibular resection, heal- val appearance of enhancing lesions on CT and marked
ing osteotomies are characterized by increased FDG cartilage or bony destruction on follow-up imaging may
uptake, but this should not hinder the interpretation if indicate tumor recurrence. Otherwise, either close fol-
adequate information is provided to the reader (Figure low-up or surgical intervention are adopted policies.
4-76). Increased FDG uptake increase by free vascular-
ized bone grafts is not commonly reported. Recurrent What Benign Changes Can Be Seen
tumor in the resection bed or flap usually appears as a
in the Vocal Cords?
focal mass, usually at the interface of the operative site
and the flap. Any area of soft tissue density within the Posttherapy changes in the vocal cords may cause asym-
flap should be considered suggestive of recurrence but metric uptake following either injury to the recurrent
also may be simulated by postoperative scan. laryngeal nerve or direct therapy to the vocal cord (Fig-
ures 4-79 and 4-80). This phenomenon can be the result
What Are the Radiation Therapy- of compensation by the contralateral vocal cord during
Induced Changes in the Head and phonation or therapy-induced changes, respectively.
Neck? Localizing asymmetric vocal cord FDG uptake is much
less of a diagnostic problem when PET/CT is used. The
Radiation therapy usually causes thickening and edema presence of associated masses on CT in this location
(Figure 4-77) of the mucosal surfaces, which may result suggests a malignant cause (Figure 4-78). In addition,
in false-positive findings. Any mass associated with if a patient has unilateral vocal cord paralysis, we have
uptake should be interpreted as suggestive of recurrence observed that the functioning contralateral cord can
(Figure 4-78). Radiation-induced necrosis of the osseous appear to have relatively increased FDG uptake com-
or cartilaginous structures can also result in ­false-positive pared to the nonfunctional side (Figure 4-80).
194 Section I Advanced Modalities: Protocols and Optimization

B
Figure 4-70 Two different patients with 6-month follow-up PET/CT study performed with low-dose CT (A) and contrast-enhanced CT (B).
A: Patient with a history of hypoglottic squamous cell carcinoma (SCC), status post left pharyngeal wall resection. B: Patient with a history of
tonsil SCC, status post resection and right elective neck dissection. There is mildly increased FDG uptake (SUVmax 3.0) corresponding to the
anatomic planes containing metallic clips (arrows). These findings, particularly, in the absence of a soft tissue density, are most consistent with
postsurgical changes that may be related to metal artifacts or adjacent muscle uptake. It is difficult to differentiate small volume recurrent disease
from inflammatory changes in this setting; thus, frequent follow-up is always recommended to exclude the possibility of recurrence (compare
with Figures 4-57 and 4-62).
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 195

SECTION I
Figure 4-71 A 59-year-old man with a history of left buccal squamous cell carcinoma, status postsurgical resection and radiation therapy. Six-
month follow-up PET/CT study performed with contrast-enhanced high-resolution CT, bone (first from left) and soft tissue windows (second
from left), demonstrates increased uptake (SUVmax 5.0) corresponding to the body of the left mandible, which shows a bone defect (arrows). The
patient has a recent history of tooth extraction in this region. These findings are most consistent with inflammatory changes related to the recent
dental manipulation. Note that in the absence of a relevant history, these findings might have been misinterpreted as recurrent disease with bony
destruction.

Continued
196 Section I Advanced Modalities: Protocols and Optimization

Figure 4-72 A: A 50-year-old man with a history of left hard palate squamous cell carcinoma (SCC; same patient as shown in Figure 4-68),
status post resection and reconstruction with free flap. Six-month follow-up PET/CT study with contrast-enhanced CT shows somewhat focally
increased FDG uptake (SUVmax 4.5) along the alveolar ridge of the left mandible (arrows). The CT portion of the study is limited due to significant
metallic artifacts emanating from dental hardware. Although it would be ideal to determine the absence of a soft tissue density in this region to
rule out a possible malignant cause, in this patient, these findings probably represent inflammatory gum disease secondary to dentures, which is
a common presentation in this patient population. Upon further inquiry, the patient was found to have recent dental manipulation resulting in
gum trauma. However, in a patient with a history of buccal SCC, these findings should raise suspicion for recurrent disease. Each patient should be
evaluated in the context of the primary diagnosis with a thorough medical history. B: A 67-year-old woman with a history of base of tongue SCC,
status post partial glossectomy, radiation therapy. Nine-month follow-up PET/CT study with contrast-enhanced CT shows increased FDG uptake
(SUVmax 6.5) along the medial gum line of the left mandible (arrows). No soft tissue mass is appreciated on the corresponding CT slice. These
findings probably represent inflammatory gum disease secondary to recent trauma or chronic irritation, which is not infrequent in this popula-
tion. Upon further inquiry, the patient was found to have started wearing dentures and was complaining about ulceration as a result of irritation.

C
Figure 4-73 A, B: Two different patients with laryngeal squamous cell carcinoma (SCC). A: Patient with recent removal of tracheostomy tube
(6 weeks prior). B: Patient with recent placement of tracheostomy tube (8 weeks prior). Note FDG uptake tracking along the device with no
definite evidence of soft tissue density on the companion contrast-enhanced high-resolution CT (arrows). This finding is consistent with inflam-
matory changes. However, close follow-up within 3 to 6 months is recommended to ensure resolution of these findings. C: Patient with a history
of laryngeal SCC, status post neopharynx reconstruction, tracheostomy removed 6 months ago, presents with progressive difficulty in swallow-
ing and pain. PET/CT study with contrast-enhanced CT shows increased FDG uptake (SUVmax 8.5) corresponding to an irregular soft tissue mass
posterior to the prior tracheostomy site obliterating the fat planes (arrows), most consistent with recurrent disease. Association of a mass on the
companion CT study should always increase the suspicion for recurrent disease and should prompt biopsy confirmation. Subsequent biopsy of
this mass revealed invasive poorly differentiated SCC.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 197

SECTION I
A

B
Figure 4-74 A 71-year-old woman with a history of tonsillar squamous cell carcinoma, status neoadjuvant therapy followed by resection, elec-
tive right neck dissection, and myocutaneous flap reconstruction. A: Six-month follow-up PET/CT study with contrast-enhanced high-resolution
CT demonstrates increased FDG uptake (SUVmax 5.8) corresponding to the posterior margin of the myocutaneous flap (arrows) and overlying
skin thickening (small arrows) with no associated mass on CT. B: Nine-month follow-up PET/CT study with contrast-enhanced CT again shows
increased FDG uptake in the same region but a decrease (SUVmax 4.1) (arrows) and resolution of uptake at the skin surface with no associated
mass on CT. These findings are consistent with postsurgical inflammatory changes. The extent and duration of tissue inflammation are dependent
on the extent of surgery and the time period between imaging and surgical intervention. These metabolic changes gradually resolve over time but
may last as long as 12 months and in some cases even longer. Follow-up imaging is complementary to conventional follow-up to rule out the
possibility of residual disease.
 A

B
Figure 4-75 Two patients with a history of squamous cell carcinoma of the tongue, status posttreatment with chemoradiation followed by
partial glossectomy. Six-month posttherapy PET/CT studies performed with contrast-enhanced high-resolution CT demonstrate significantly
increased diffuse uptake (SUVmax 8.2) corresponding to the tongue with no appreciable mass on the accompanying contrast-enhanced CT
(A; arrows) and increased uptake (SUVmax 4.9) in the genioglossus muscle again with no associated mass (B; arrows). In the absence of a dominant
mass, these findings are consistent with postglossectomy changes related to compensatory use of muscle groups that are not usually involved in
speech and swallowing functions, resulting in significantly increased physiologic uptake in the muscles that are utilized.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 199

Figure 4-76 A 67-year-old woman with a history of floor of mouth squamous cell carcinoma, status post treatment with chemoradiation

SECTION I
followed by composite resection involving partial mandibulectomy and mandibuloplasty with titanium rod placement. Six-month posttherapy
PET/CT study performed with contrast-enhanced high-resolution CT (bone window) demonstrates diffusely increased FDG uptake (SUVmax 4.2)
corresponding to the site of mandibuloplasty and associated rods with no appreciable destructive change (arrows). It is challenging to note erosive
or destructive changes in the presence of extensive surgical change associated with surgical hardware on the accompanying contrast-enhanced CT.
Titanium rods are not known to cause increased uptake, but bone remodeling may result in this pattern of diffuse uptake.

B
Figure 4-77 Two patients with a history of tongue supraglottic squamous cell carcinoma, status post treatment with chemoradiation. Three-
month posttherapy PET/CT studies performed with contrast-enhanced high-resolution CT demonstrate edematous changes (arrows) and mucosal
thickening of the supraglottic larynx with diffuse low-grade and irregular FDG uptake (SUVmax 3.2). These metabolic changes gradually resolve
over time, usually preceding the resolution of edema; however, they may last longer than a year in some cases. It is not difficult to recognize the
pattern of low-grade uptake; however, in cases with high risk of recurrence, these findings may lead to equivocal readings. In most of these cases
biopsy is contraindicated due to the possibility of aggravation of inflammation and necrosis in the radiotherapy field. Follow-up imaging is sig-
nificantly helpful and complementary to conventional follow-up to rule out the possibility of recurrence.
200 Section I Advanced Modalities: Protocols and Optimization

Figure 4-78 A 58-year-old man with a history of left vocal cord squamous cell carcinoma, status post laser excision. Twelve-month follow-up
PET/CT study performed with contrast-enhanced high-resolution CT demonstrates increased uptake (SUVmax 7.6) corresponding to a soft tissue
nodule in the anterior commissure (arrows), consistent with recurrent disease, which was subsequently proven by biopsy. Note that association of
FDG uptake with a mass significantly increases the likelihood of recurrent disease (compare with Figure 4-69).

B
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 201

Figure 4-79 A 64 year-old patient with a history of left vocal cord squamous cell carcinoma, status postradiation therapy 9 month prior to

SECTION I
PET/CT imaging. A: PET/CT study performed with contrast-enhanced high-resolution CT reveals FDG uptake in both vocal cords (small horizontal
arrows) and cricoarytenoid muscles (small vertical arrows), slightly more prominent in the right vocal cord. There is no appreciable nodule or mass
on the vocal cords on the associated CT slice. The patient was noted to speak loudly during the FDG injection and uptake period. This uptake pat-
tern probably reflects the activation of intrinsic laryngeal muscles during phonation. Subsequent laryngoscopy was unremarkable. B: At 3-month
follow-up study, the patient kept silent during the FDG injection and uptake period. The previously noted uptake in the vocal cords had resolved,
proving the previous uptake to be of physiologic nature. It is essential that patients with a history of head and neck cancer be kept silent during
the uptake period of FDG to prevent uptake in the vocal cords, which may lead to false-positive findings.

B
Figure 4-80 Two patients showing various degrees of physiologic vocal cord uptake. A: Patient with a history of treated base of tongue squa-
mous cell carcinoma, status post primary therapy, now referred for follow-up study. Axial sections of the FDG PET/CT study with low-dose CT
demonstrate symmetric FDG uptake in the thyroarytenoid (horizontal arrows) and posterior cricoarytenoid muscles (vertical arrows) reflecting acti-
vation of intrinsic laryngeal muscles during phonation. B: Axial sections of the FDG PET/CT study with low-dose CT demonstrate FDG uptake in
the right thyroarytenoid (horizontal arrow) and posterior cricoarytenoid muscle (vertical arrow) reflecting activation of intrinsic laryngeal muscles
during phonation. There is no uptake in the corresponding muscles on the contralateral site, which is consistent with paralysis of the vocal cord at
this site. Although this pattern of uptake is characteristic for activated vocal cords, accompanying CT further confirmed the absence of any patho-
logic mass in this region. It is essential that patients be kept silent during the uptake period of FDG to prevent uptake in the vocal cords, which
may lead to false-positive findings.
202 Section I Advanced Modalities: Protocols and Optimization

Figure 4-81 A 70-year-old man recently diagnosed with piriform sinus squamous cell carcinoma (SCC), referred for PET/CT study for further
evaluation of extent of disease (same patient as shown in Figure 4-26, B). PET/CT imaging performed with contrast-enhanced high-resolution
CT demonstrates a soft tissue mass projecting off the epithelial surface of the right maxillary sinus (arrows), which demonstrated significantly
increased FDG uptake (SUVmax 28.0). This mass is highly suggestive of a malignant process. However, metastasis is unlikely due to the unusual
location. A second primary of the maxillary sinus can be a consideration. Subsequent excisional biopsy of the maxillary sinus mass revealed a
sinonasal oncocytic schneiderian papilloma. Based on these findings, the patient’s disease was staged as a T3N2bM0 hypopharyngeal carcinoma
(primary tumor and metastatic lymph nodes not shown). The patient subsequently underwent chemotherapy and hyperfractionated radiation
therapy for hypopharyngeal SCC, followed by selective neck dissection. He responded well to therapy, with no evidence of disease after follow-up
of 8 months, which included repeat PET/CT and diagnostic CT studies. The patient is currently without recurrence of maxillary sinus papilloma.

HOW DO THE CERVICAL LYMPH WHAT BENIGN TUMORS CAN

NODES CAUSE FALSE-POSITIVE CAUSE AVID FDG UPTAKE?
READINGS?
Some benign tumors, including pleomorphic adenoma,
Level I to II lymph nodes can increase their glucose uti- Warthin tumor (Figure 4-81), inverted papilloma (Sch-
lization because they are part of an important defense neiderian cyst) (Figure 4-82), thyroid adenoma, and
system (Figures 4-13, B, 4-35, and 4-36, B). Because Thornwaldt cysts, can accumulate FDG at significant
FDG is not specific to malignancy, it is taken up by levels. Thus, the expected pattern of distribution should
inflammatory processes, which may cause false-positive be considered while interpreting imaging, and caution
findings in the cervical lymph nodes. In these cases, fol- should be exercised when an extraordinary finding is
licular dendritic cells in germinal centers, which form a encountered.
system of highly efficient antigen-presenting cells with The PET/CT reader can avoid errors by recognizing
preferential FDG uptake, were suggested to be the prin- certain common benign physiologic and postoperative
cipal cause of false-positive findings in nodal staging. presentations. Follow-up studies and a baseline study are
Nonetheless, when CT and MRI data are individually important adjuncts for accurate interpretation of PET/
compared to PET results, the specificity is still in favor of CT studies of various challenging settings in patients
FDG PET by 10% at approximately 85%. with head and neck cancer.
 Chapter 4 PET/CT Imaging In Squamous Cell Carcinoma of the Head and Neck 203

SECTION I
A

B
Figure 4-82 Two patients with a history of treated laryngeal (A) and tonsillar carcinoma (B), respectively, referred for 12-month follow-up
FDG PET/CT study. There is no baseline study for comparison. Axial PET/CT images demonstrate a small nodule within the right parotid gland
(A) and left parotid gland (B), both demonstrating smooth borders (arrows) and increased FDG uptake (SUVmax 6.9 and 3.6, respectively). These
findings are consistent with parotid incidentalomas. Subsequent biopsy of the right parotid gland lesion revealed Warthin’s tumor, which is a
benign neoplasm of the salivary glands. The left parotid gland lesion was not biopsied. However, this finding was persistent on multiple follow-up
studies, which may represent either a pleomorphic adenoma or a Warthin’s tumor.
204 Section I Advanced Modalities: Protocols and Optimization

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 chapter 5

Diagnostic Angiography
Stephan Meckel and Stephan G. Wetzel

INTRODUCTION
vigorous and frequent flushing is required. The catheter
In 1927, the intriguing Portuguese neurologist and poli- end is placed a few centimeters proximal to the origin
tician Egas Moniz performed the first diagnostic cerebral of the brachiocephalic trunk with the pigtail loop in the
angiogram in a 48-year-old male patient with posten- coronal plane. Contrast injections are performed using
cephalitic Parkinson disease. He injected a 70% solu- a power injector (rate 20–30 ml/s, total volume 40–50
tion of strontium bromide into the surgically exposed ml) and filming is performed in the left anterior oblique
carotid artery and produced a series of four angiographic projection (30–40 degrees).
images. The patient died 8 hours later of thromboem-
bolic complications. Since then, the art and science of Common Carotid Arteries
cerebral angiography have progressively developed as a
result of improvements in imaging capabilities and tech- What Are the Most Optimal Techniques/
nical equipment and safer contrast media. In the setting Catheters for Accessing the Common Carotid
of constantly improving, utterly noninvasive computed Arteries Routinely and in Difficult Situations?
tomographic angiography (CTA) and magnetic reso- Selective catheterization of the common carotid arteries
nance angiography (MRA) capabilities, cerebral catheter in persons younger than 40 years usually can be accom-
angiography remains an important tool for evaluation plished using small-diameter standard cerebral cath-
of the cerebral vasculature today, as in the past. Clearly, eters (4–5.5F) with simple shapes (e.g., 5F Berenstein/
if equivalent information can be obtained by noninva- UCSF-II, Cordis, Bridgewater, NJ, USA) in combination
sive means, then this method is not indicated. However, with soft-tipped 0.035-inch guidewires (e.g., Bentson,
even though today it is seldom the first study of choice Cook Medical Inc., Bloomington, IN, USA). In older
for imaging of central nervous system (CNS), diagnostic patients, vessel elongation, tortuosity, and dilatation
neuroangiography is still considered the reference stan- may require the use of larger-diameter and hence stiffer
dard for imaging of a variety of neurovascular diseases catheters (e.g., a 7F Berenstein) in combination with
that affect the intracranial and extracranial vasculature. stiffer guidewires (e.g., hydrophilic coated 0.035-inch
Apart from its capability of vessel selective or superse- Terumo Glidewire, Terumo Medical Corporation, Som-
lective imaging, the main reason is the unique spatial erset, NJ, USA). Alternatively, a reverse-curve catheter
and time resolution of diagnostic cerebral angiography may be used. However, selective catheterization beyond
that still is unbeaten by all current noninvasive means in the common carotid bifurcation is difficult using this
the armamentarium for neurovascular imaging. Despite catheter and therefore is not generally recommended.
technologic advances, a cerebral angiogram still carries The basic catheterization technique using a standard
a low risk of potentially devastating permanent neuro- cerebral catheter consists of bringing the catheter and
logic damage; hence, this procedure should be under- inserted guidewire tip to tip within the proximal aor-
taken only for strong indications by trained operators. tic arch with the tip usually facing downward. Coun-
Such training should not only comprise technical com- terclockwise rotation and simultaneous slow backward
petence but also a sound knowledge of relevant neuro- pulling applied so that the catheter tip is directed cepha-
vascular anatomy and pathology. lad usually will result in engagement of the great vessel
ostia. The novice angiographer must be trained on this
ANGIOGRAPHIC TECHNIQUE maneuver, otherwise the applied torque will build up in
the shaft of the catheter and then be released suddenly
into the tip, causing the catheter to make 360-degree
Aortic Arch
resolutions. For more selective catheterization, the
Problem Solving: How and What Are the guidewire is then advanced to approximately the level
Reasons for Imaging the Aortic Arch? of C7 (above the T1 transverse process), and the cath-
The arch aortography is only infrequently required in eter is passed over the immobilized guidewire. Advanc-
cerebral angiography if proximal stenosis of the great ing the catheter all the way to the guidewire tip should
supraaortic arteries in suspected (e.g., in Takayasu arte- be avoided because this increases the likelihood of ves-
ritis, dissecting aneurysm, and neurofibromatosis). It sel dissection or vasospasm. In older patients, it may
usually is performed using a 5F or 6F pigtail catheter be necessary to advance a greater length of guidewire
that has multiple side holes and an end hole. Therefore, to provide sufficient support for catheter advancement,

211
212 Section II  Procedures

and the tip of the guidewire should be guided fluoro- result in permanent neurologic deficit and even death.
scopically into the external carotid artery (ECA). The Meticulous technique and scrupulous attention to cath-
guidewire is then withdrawn and the catheter imme- eter flushing are requisite if serious complications are to
diately flushed. Before selective catheterization of an be prevented. In young female patients and particularly
internal carotid artery (ICA), the common carotid artery those with a history of migraine headaches, the likeli-
should be routinely injected to view the carotid bifur- hood of iatrogenic vasospasm, even with gentle guide-
cation. These views can be documented as either saved wire and catheter manipulations, is increased; therefore,
roadmap images or an angiographic series. prophylactic application of topical nitropaste may be
In cases of a bovine-type arch branching pattern, considered. If significant atherosclerotic bifurcation dis-
selective catheterization of the left common carotid ease or evidence of arterial dissection is present, then
artery might require a catheter with a relatively acute selective ICA catheterization is best avoided. It is gen-
angled primary curve or tip such as a 7F Berenstein or a erally advised to perform selective ICA catheterization
reverse-curve catheter. under digital roadmap guidance, particularly if kinking
With increasing age and in the presence of hyper- of the proximal or coiling of the distal cervical ICA (ton-
tension, unfolding and elongation of the aorta result sillar loop) is present. The tip of the guidewire should be
in the great arteries arising proximal to the arch apex, advanced no further than the C2 level because the rela-
making selective catheterization with standard 4F or 5F tively fixed petrous segment is more prone to dissection.
cerebral catheters (e.g., Berenstein) more difficult. This Ideally it should be positioned within a relatively straight
may require the use of reverse-curve catheters such as vessel segment so that its distal curve conforms to that
the Simmons 2/Sidewinder 2 (Angiodynamics, Latham, of a similar curve of the surrounding vessel in order to
NY, USA). Various techniques for re-forming their ­distal minimize trauma to vessel intima, as occurs with subin-
shape prior to vessel selection have been described. timal injection or dislodgement of atheromatous plaque.
However, counterclockwise rotation and forward advan­ A contrast injection rate of 5 to 7 ml/s for a total of
cement with the catheter tip against the apex of the arch 7 to 9 ml usually is sufficient; however, this rate and
and the guidewire proximal to the major bend of the volume need to be reduced in the presence of down-
catheter usually is successful. Once the catheter tip has stream stenosis (e.g., cerebral vasospasm or Moyamoya
engaged the vessel ostium, advancement of the tip is disease) or alternatively may need to be increased with
accomplished by withdrawing the proximal end. The high-flow states such as arteriovenous malformations
reverse-curve catheter also may be preferred for evalua- or fistulae. Preliminary assessment of intracranial flow
tion of carotid bifurcation disease because only a short with hand injection of contrast is useful if these condi-
length of leading guidewire is required, thus reducing tions are suspected or are being investigated. Standard
the likelihood of guidewire impingement against an intracranial carotid views include lateral and AP projec-
atherosclerotic plaque. tions (petrous ridges projected midway between orbital
Standard projections for demonstrating the carotid roof and floor). A suitable filming rate is three to four
bifurcation are anteroposterior (AP) and lateral. In cases images per second for 4 to 5 seconds, followed by one
of suspected ICA stenosis, both oblique views are often image per second for 7 seconds. The initial filming rate
necessary to display plaques in their entirety and to is increased when investigating high-flow vascular mal-
detect the maximum area of stenosis. For the bifurca- formations.
tion, a lower injection rate (5–8 ml/s, total volume 5–8
ml) than for intracranial circulation (6–8 ml/s, total vol- Vertebral Arteries
ume 7–10 ml) is applied because the distal runoff does
not require visualization. A suitable filming rate is four Problem Solving: What Are the Most Optimal
images per second for 4 seconds, followed by 1 image Techniques/Catheters for Accessing the Vertebral
per second for 8 seconds. In the case of presumed ICA Arteries Routinely and in Difficult Situations?
occlusion, prolonged filming is necessary, otherwise The vertebral arteries (VAs) usually are the first branches
delayed faint anterograde opacification of the cervical of the subclavian arteries. Prior to vertebral angiography,
ICA may be missed—a “string sign” of a critical ICA any previous magnetic resonance imaging (MRI)/MRA/
stenosis. Delayed opacification of the carotid siphon CTA results should be reviewed and the dominant VA
does not necessarily imply patency of the cervical ICA, indentified. A roadmap image of the subclavian artery
because this is usually due to the ipsilateral ECA collat- should be generally obtained prior to selective catheter-
eral vessels anastomosing either directly with the carotid ization. If there is any suspicion of a VA origin stenosis,
siphon or with the ipsilateral ophthalmic artery (OA). then formal angiography is performed. In contradis-
tinction to the common carotid arteries, atherosclerotic
narrowing is common at the origins of the VAs. The VA
Internal Carotid Arteries
origin usually is best demonstrated using a mild cranial
Problem Solving: What Are the Most Optimal and contralateral oblique projection (Figure 5-1). If a
Techniques/Catheters for Accessing the Internal significant stenosis is confirmed, then vertebral angi-
Carotid Arteries Routinely and in Difficult ography is performed using subclavian artery contrast
Situations? injection (6–8 ml/s, total volume 12–16 ml) with an
Selective catheterization of the ICAs should be performed inflated pressure cuff on the ipsilateral arm. We generally
only by neuroangiographers with sufficient experience perform selective catheterization of the VAs using digital
and skill. Vessel damage and/or thromboembolism can roadmap guidance. The proximal VA often is ­tortuous.
 Chapter 5 Diagnostic Angiography 213

from a power injector. Generally, a double-flush tech-

SECTION II
nique with heparinized saline (1,000 units per liter for
pediatric cases, 3,000–6,000 units per liter for adults) is
used. A syringe with 5 to 10 ml is attached to a stopcock,
which is attached to the hub of the catheter. The syringe
is gently aspirated with approximately 2 to 3 ml of
blood, checking for clots. After the first syringe is discon-
nected, a second clean flush syringe with heparinized
saline is connected to the end of catheter and aspirated
back slightly. The tip of the syringe should be oriented
downward so that any air bubbles will rise away from
the hub of the catheter. It often is helpful to tap the side
of the syringe to force any bubbles toward the plunger.
The syringe is then injected with a continuous stream
of heparinized saline. The stopcock is turned off midin-
jection, ensuring that the entire length of the catheter,
including the tip, has been filled up with saline. This
last point, although seemingly trivial, is very important.
If the injection is stopped before the stopcock is turned
to the off position, blood could backflow into the tip of
the catheter, clot, and produce a thromboembolus.
After the syringe has been removed from the end of
Figure 5-1 Right subclavian artery angiogram, mild Towne and a catheter, the hub should be irrigated. This is best per-
contralateral oblique projection, depicting typical atherosclerotic formed using a separate syringe filled with heparinized
high-grade stenosis (pinhole) at the origin of the right vertebral artery saline with an angiocatheter (20-gauge) attached to the
(small black arrow). (Courtesy Dr. Tejinder Pal Singh, Perth.) tip. This setup allows injection of a jet of flush directly
into the hub for irrigation of any residual blood.
On withdrawal of a guidewire from a catheter, a suck-
In this situation the guidewire and catheter are not ing or hissing sound may be heard. This implies that the
passed beyond a sharp bend. Otherwise, the guidewire end hole of the catheter is obstructed, often because it is
and catheter usually are not passed beyond the C4 level resting against the arterial wall. If this occurs, withdraw
because the VAs are smaller and more prone to iatro- the catheter 1 cm without concurrent application of suc-
genic vasospasm than are the carotids. Evaluation of the tion, which would risk intimal damage. Once stationary,
cervical segment of the VA can be performed in the ipsi- the catheter is gently aspirated until unrestricted back
lateral oblique plane (4–6 ml/s, total volume 4–6 ml). return of blood is confirmed. A gentle hand injection of
Standard intracranial views include the Towne AP view contrast is performed to ensure free contrast flow from
(petrous ridges projected above the orbital roofs) and the tip, thus avoiding a forceful wedge injection into
the lateral projection. A Waters AP view (petrous ridges a subintimal flap or vessel in spasm. A more vigorous
projected at the base of the maxillary antra) may be use- hand injection is then performed to gauge the flow rate
ful for better demonstration of the basilar artery (BA) and to better view the regional vascular anatomy.
and its termination (Figure 5-2). The contrast injection
rate depends on the vessel caliber (4–6 ml/s, total vol- COMPLICATIONS AND RISK
ume 6–9 ml). The film acquisition rate is three images FACTORS
per second for 4 seconds, followed by one image per
second for 7 to 8 seconds. With selective angiography it Every cerebral angiogram carries a potential risk of
usually is possible to obtain reflux into the contralateral stroke and even death. The risks may be broadly divided
posterior inferior cerebellar artery (PICA; Figure 5-2, B). into those associated with the arterial puncture (local),
Prior to any mechanical contrast injection, intracranial those associated with contrast media or other admin-
runoff should be assessed with preliminary hand injec- istered drugs (systemic), and neurologic complications
tion, because hypoplasia of the distal nondominant VA related to endovascular manipulations.
occurs at a frequency of 5% to 10%.
Nonneurologic Complications
Basic Safety Advice
What Are Some Common Nonneurologic
What Are the Most Optimal Techniques for Complications, and What Are the Best Ways
Preventing Air Bubbles and Thrombus Formation to Prevent Them?
in Catheters? Local complications include groin hematoma, retroperi-
Once in the body, a catheter should be flushed using toneal hemorrhage, pseudoaneurysm formation, arterio-
a continuous irrigation system or every 90 to 120 sec- venous fistulae (AVFs), femoral nerve damage (usually
onds (on average) before and after each wire exchange. self-limiting), arterial dissection, groin infection, sepsis,
It also should be flushed just prior to connecting to a deep venous thrombosis, and pulmonary embolism.
power injector and immediately after disconnecting In infants, avascular necrosis of the femoral head as a
214 Section II  Procedures

A B

C D
Figure 5-2 Early (A) and slightly later (B) arterial phases, Waters anteroposterior views, of a left vertebral angiogram showing the basilar artery
and its branches. Subsequent reflux into the right V4 segment of the vertebral artery (VA) is shown. A: Left posterior inferior cerebellar artery
(PICA; large black arrow) shows an uncommon high origin from the basilar artery (large white arrow). Both anterior inferior cerebellar arteries
(AICAs) (small black arrows) demonstrate characteristic lateral loops. Multiple fine lateral pontine-perforating arteries arising from the posterolat-
eral basilar artery surface are visualized lateral to the basilar artery (small white arrows). Both superior cerebellar arteries (SCAs) are shown to arise
just below the basilar artery bifurcation (black arrowheads). B: Subsequent later arterial phase, Waters anteroposterior view, showing reflux into the
right V4 segment (large black arrow) with filling of a normally located right PICA (small black arrows). The peripheral “stepladder”-configured hemi-
spheric branches of the SCA are shown (small white arrows). C: Early arterial phase of a left vertebral angiogram, lateral view, showing the cerebellar
arteries and the posterior cerebral artery branches. Reflux into the right VA and both posterior communicating arteries (black arrowheads) is shown.
1, Right PICA (originates from VA); 2, left PICA (originates high from basilar artery); 3, AICA (typical M-shaped configuration); 4, SCA; 5, P1 seg-
ment; 6, perforating branches (anterior and posterior thalamoperforating arteries); 7, P2 segment; 8, medial posterior choroidal artery; 9, lateral
posterior choroidal artery; 10, splenial branches (posterior pericallosal artery); 11, parietooccipital artery; 12, calcarine artery. D: Subsequent later
arterial phase of left vertebral angiogram, lateral view, depicting normal vascular blushes in the choroids plexus (large black arrows) and along the
dorsal surface of the splenium of the corpus callosum (small black arrows). Note faint vascular blushes of the cerebellum with demarcation of the
great horizontal fissure of the cerebellum (black arrowheads).

consequence of vascular stenoses or occlusions is a rare complications is low (0.6%) in meta-analysis. Permanent
complication. The risk of significant groin bleeding is disability as a sequela of a nonneurologic complication
dependent on many factors, such as anticoagulation, is extremely rare (0.03%). A groin hematoma requiring
sheath size, and use of puncture site closure devices. medical therapy or surgery occurs very seldom (incidence
The reported overall rate of serious nonneurologic 0.03%–0.2%). Minor groin hematomas are reported to
 Chapter 5 Diagnostic Angiography 215

occur in 0.5% to 8.1%.The rate of groin hematomas or spasm). Rare neurologic sequelae include transient

SECTION II
was higher in studies of patients receiving heparin as a cortical blindness, transient global amnesia, involuntary
bolus than in studies that advocated heparinized saline leg movements (monoballismus), and transient senso-
flushing. The most common systemic complications are rineural deafness. The etiologies of these rare phenom-
nausea, vomiting, and/or transient hypotension (1.2%), ena are speculative but in some cases may be related to
followed by headaches (0.8%). Severe allergic reactions, contrast toxicity. A history of sickle cell anemia may be
such as anaphylaxis (0.03%), are rare. In patients with a relevant because contrast media may initiate intravascu-
suspected history of contrast allergy, a pretreatment regi- lar sickling, resulting in cerebral ischemia. In addition,
men with diphenhydramine (e.g., 50 mg given intrave- patients with Ehlers-Danlos syndrome (particularly type
nously one hour prior to the procedure) is performed. IV) are especially predisposed to significant vessel injury
In high-risk patients (e.g., those with a previous episode with catheter angiography.
of anaphylactoid reaction), additional premedication A risk of catheter angiography unique to patients
with corticosteroids (e.g., prednisone 50 mg orally every with subarachnoid hemorrhage (SAH) secondary to
6 hours for three doses, ending 1 hour before the proce- cerebral aneurysm rupture is that of rebleeding during
dure) as well as notification of the anesthesiology staff contrast injection due to increased arterial pressure. The
before the case begins is advised. risk of this extremely rare complication is well below
Acute renal failure is very rarely encountered after the risk of rebleeding following SAH (4% in the first 24
a diagnostic angiogram (0.02%). It usually occurs in hours, then 1%–2% for the next 4 weeks). Thus, there is
patients with preexisting renal impairment (particularly no rationale for withholding catheter angiography from
in those with a history of diabetes mellitus or multiple patients who suffer from this very serious condition and
myeloma) receiving a relatively large dose (>4 ml/kg) require accurate and prompt diagnosis and treatment.
of intravascular contrast media. Adequate hydration of
these at-risk patients before, during, and after the pro- Transient and Permanent
cedure is imperative. Life-threatening lactic acidosis is
Neurologic Deficits
a potential complication in diabetic patients receiving
oral metformin. The current recommendation is that In two large-scale prospective studies (19,826 and 2,899
this medication not be administered until 48 hours after cerebral angiography procedures, respectively), the over-
the procedure assuming normal renal function. all rate of neurologic complications that occurred within
Dion et al. noted that nonneurologic complica- 24 hours of the examination varied between 1.3% and
tions are significantly related to age greater than 50 2.63%. The substantial majority of these complications
years, hypertension, transient ischemic attack (TIA) as were transient (<24 hours) in 0.7% to 2.09% or were
an indication, and the presence of a carotid bruit. Care reversible (24 hours to 7 days) in 0.2% to 0.36%. Stroke
should be taken that the puncture is below the inguinal with permanent disability (>7 days) occurred in only
ligament, which reduces the likelihood of retroperito- 0.14% to 0.5% of examinations, and death related to
neal hemorrhage. Extra precaution is also required for a neurologic condition occurred in 0.05%. The indica-
patients receiving antiplatelet medications and/or anti- tion with the highest rate of neurologic complications
coagulation or with preexistent coagulopathies, patients was atherosclerotic cerebrovascular disease (4.0%), fol-
receiving long-term steroids or with a history of chronic lowed by SAH (3.2%). Patients with a history of fre-
renal failure, patients who previously have undergone quent TIAs were 67% more likely than those without a
aortofemoral bypass surgery, those with larger sheath history to have a neurologic complication. Other factors
sizes, or those in whom repeated arteriotomies have for increased risk of neurologic complications include
been performed. advanced age (>55 years), preexisting cardiovascular
disease (coronary artery disease, hypertension, periph-
Neurologic Complications eral vascular disease), prolonged fluoroscopic times
(>10 minutes), and arteriovenous malformation as the
What Are Some Common Neurologic indication. For the pediatric population, cerebral cath-
Complications, and What Are the Best eter angiography performed by experienced operators
Ways to Prevent Them? has been shown to be a safe procedure.
Neurologic complications are usually, but not always, In a meta-analysis by Cloft et al., the overall neuro-
the result of embolism (clot, plaque, air, or foreign logic complication rate was lower in patients with SAH,
body) or iatrogenic dissection. The most common aneurysm, or arteriovenous malformation compared
cause implicated is thromboembolism from catheters with the rate in patients with ischemic stroke (0.8% vs
or guidewires. Thrombi may most likely develop inside 3.0%), as was the risk of permanent neurologic compli-
the catheter if the guidewire is withdrawn into the cath- cation (0.07% vs 0.7%).
eter, allowing blood to stagnate within this dead space. In two large-scale studies that enrolled patients over
Therefore, the importance of avoiding this dead space longer periods of time, the rate of neurologic compli-
and keeping the guidewire manipulations to a mini- cations decreased from 2.1% to 0.9% over 5.5 years
mum time is emphasized. Other potential pathophysi- and from 3.8% to 0.57% over 24 years, respectively.
ologic mechanisms include platelet activation, changes This significant decrease of complication rates in more
in clotting factors, and neurotoxicity of contrast agents. recent years was attributed to improvement in equip-
Vessel rupture may occur if an excessively forceful injec- ment and angiographer skill and to the introduction of
tion is made into an undersized artery (due to anatomy standardized use of heparinized catheter flush systems.
216 Section II  Procedures

Willinsky et al. noted that the improved complication medium and probably are caused by tiny air bubbles
rate correlated with a lower percentage of patients being dissolved in contrast medium. Cerebral angiographic
examined for carotid stenosis or ischemic stroke and procedures with systematic use of air filters between the
a lower percentage of patients with cardiovascular dis- catheter and both the contrast medium syringe and the
eases. Although not yet analyzed by direct comparison, catheter flushing have shown a significant reduction in
the liberal use of a heparin bolus may be a benefit, as silent ischemic events (6% vs 22%). The same study
comparison of different studies showed similar over- showed that systemic heparin treatment (initial bolus of
all neurologic complication rates but lower permanent 50 international units per kilogram of body weight fol-
complication rates in studies that used a heparin bolus. lowed by a maintenance dose of 25 international units
The analysis of risk predictors and complication rates per kilogram of body weight per hour) resulted in an
substantiates the argument that patients at higher risk identical reduction of silent ischemic events.
(e.g., those with atherosclerosis, advanced age, vascu-
litis) should primarily undergo noninvasive imaging. Level of Experience
Complications still occur in patients without these
risk factors, but at a relatively low rate; therefore, the What Is the Influence of Operator’s Experience
indications for catheter angiography should be care- on Complication Rates?
fully balanced. At our institution, all diagnostic cere- The contributing effect of the operator’s experience on
bral angiography procedures, except those performed the procedural neurologic complication rate remains still
in patients with acute intracranial hemorrhage, usually unclear. Kaufmann et al. found that the involvement of a
are performed with a heparin bolus (70 international resident and/or fellow in the procedure was significantly
units per kilogram of body weight) that is given directly associated with a decreased risk of neurologic outcome.
after the femoral sheath is inserted. Puncture site closure However, other investigators found no difference or dem-
devices are preferentially used. If these devices cannot onstrated a nonsignificant increase in neurologic com-
be inserted, strict immobilization and local compres- plications if the examination was performed by fellows
sion are used to prevent the development of hematoma alone compared to those performed by neuroradiology
at the puncture site. In rare cases of bleeding at the staff alone. Interestingly, Willinsky et al. found a signifi-
puncture site, heparin can be reversed with protamine. cantly higher neurologic complication rate when the fel-
low and staff together performed the cerebral angiogram.
The majority of these cases comprised complex proce-
Silent Emboli
dures with longer fluoroscopic times and consisted of
What Are Silent Ischemic Events, and What are patients who were slightly older and had a higher rate
the Best Ways to Minimize Them? of cardiovascular disease, carotid stenosis, and ischemic
With the advent of diffusion-weighted magnetic reso- stroke. In another study, the incidence of silent ischemic
nance imaging has come the realization that clinically events studied with diffusion-weighted imaging was sig-
apparent stroke may be only the “tip of the iceberg” nificantly lower when the angiogram was performed by
regarding neurologic complications of cerebral angiogra- an experienced senior investigator than when the proce-
phy given that clinically silent cerebral microembolism dure was performed by a junior neuroradiologist.
occurs more commonly than overt neurologic complica-
tions. The reported incidence of silent microemboli that EVALUATION OF CRANIAL
are visible on diffusion-weighted imaging varies widely VASCULATURE ON ANGIOGRAPHIC
(range 9%–26%), depending on the cited source. How-
VIEWS
ever, the series that reported higher incidences (18.5%–
26%) included both diagnostic and neurointerventional
Great Supraaortic Arteries
procedures in the analysis, and the latter is associated
with a higher risk of thromboembolism. Therefore, a What Are Common Variants of the Great
more realistic estimation for the risk of silent emboli Supraaortic Arteries?
from diagnostic catheter angiography alone is likely in The typical anatomy of the great vessels that arise from the
the range from 9% to 15%. Similar to the case of overt aortic arch is in branching order of the innominate artery
stroke, preexisting vasculopathy, hypercoagulable state, or brachiocephalic trunk, the left common carotid artery,
long fluoroscopic time, high dose of contrast media, and the left subclavian artery. This anatomy is seen in
difficult vessel catheterization, and use of additional 65% to 70% of cases. The second most common variant
catheters have been identified as risk factors for the of aortic arch branching occurs when the left common
development of silent emboli. The exact pathomecha- carotid artery has a common origin with the innomi-
nism of silent ischemic events is still subject to debate. nate artery (13%) (Figure 5-3). This variant is most often
Possible causes are air embolism or small blood clots termed a bovine aortic arch, which is a misnomer because
from catheters, arteriosclerotic plaques scraped off from solely a single great vessel originates from the aortic arch
the vessel wall, vessel wall reaction to contrast medium in cattle. A similar but less common variant occurs when
in vasculitis, or even local thrombosis. Bendszus et al. the left common carotid artery originates directly from
confirmed injected air as a source of silent emboli. the innominate artery but more distally rather than as
Air bubbles can be identified by transcranial Doppler a common trunk (9%). These variants of left common
sonography as microembolic signals. Dense showers carotid artery origin are found more often in blacks
of such signals are only related to injections of contrast compared with whites. Other less common anatomic
 Chapter 5 Diagnostic Angiography 217

Right carotid

SECTION II
Right carotid
artery Left carotid Right artery Left carotid
Right artery
artery vertebral
vertebral
Left artery Left
artery
vertebral vertebral
artery artery
Right Right
subclavian Left Left
subclavian subclavian
artery artery subclavian
artery artery
Innominate Innominate
artery artery

A B
Figure 5-3 The most common aortic arch branching pattern has a separate origin for the innominate, left common carotid, and left subclavian
arteries. The second most common pattern of aortic arch branching has a common origin for the innominate and left common carotid arteries.
This pattern has been referred to as a “bovine arch”. (Redrawn from Layton KF, Kallmes DF, Cloft HJ, Lindell EP, Cox VS. Bovine aortic arch variant
in humans: Clarification of a common misnomer. AJNR Am J Neuroradiol 2006;27:1541-1542.)

A B
Figure 5-4 Anteroposterior (A) and lateral (B) views of a left common carotid angiogram showing the normal extracranial course of the
internal (ICA) and external carotid artery (ECA) and the ECA branches. The carotid bulb is indicated by the black arrowheads. The ICA initially
lies behind and lateral to the ECA. As the cervical ICA ascends (white arrows), it crosses behind and then courses anteromedially to the main ECA
trunk. 1, Superior thyroid artery; 2, lingual artery; 3, facial artery; 4, ascending pharyngeal artery; 5, main ECA trunk; 6, occipital artery; 7, posterior
auricular artery; 8, maxillary artery; 9, middle meningeal artery; 10, superficial temporal artery; 11, ascending palatine artery (facial artery branch).

variations include a direct origin of the left VA from the bifurcation usually is located at the C3–5 level (82%),
aortic arch, usually between the left common carotid which fluoroscopically approximates to just below the
and left subclavian arteries (6%) and an aberrant right angle of the mandible. The carotid bifurcation usually
subclavian artery that arises distal to the left subclavian is higher in children at C2–4 (80%), and the left side
artery and may course posterior to the esophagus. More usually is slightly higher than the right. It may occur as
than 20 different aortic arch configurations have been high as C1 and as low as T2 as a normal variation. In
described, but those specifically described here are by far older patients, a fleck of calcium within a bifurcation
the most commonly encountered. plaque can serve as a useful radiographic landmark. The
common carotid artery does not have any significant
Common Carotid Arteries branches and widens near its termination. This bulbous
dilatation is carried into the ICA origin and is referred
What Are the Landmarks for Imaging to collectively as the carotid sinus (Figure 5-4). The ICA
the Common Carotid Arteries? invariably arises posterior to the ECA and, in most cases,
The right common carotid artery usually originates at laterally. Thus, an ipsilateral anterior oblique or lateral
the level of the right sternoclavicular joint. The carotid view usually is optimal for displaying the bifurcation;
218 Section II  Procedures

however, pinhole or web-like high-grade stenoses may

be underestimated unless multiple oblique projections
are performed.

Internal Carotid Arteries

What Are the Anatomic Segments, Common
Variants, and Branches of the Internal Carotid
Arteries?
Several systems for classifying the ICA segments
have been proposed. The classification proposed by
Bouthillier et al. is practical as it uses a numerical scale in
the direction of normal blood flow similar to the other
major brain supplying arteries, and it takes into account
new anatomic information and clinical considerations
(Figure 5-5). Seven anatomically distinct segments are
described according to their adjacent structures and the
compartments they traverse (Figure 5-6):
C1 = Cervical
C2 = Petrous
C3 = Lacerum
C4 = Cavernous
C5 = Clinoid
C6 = Ophthalmic
C7 = Communicating

C1 (Cervical) ICA
The first ICA segment can be divided in two parts: the Figure 5-5 According to the classification by Bouthillier et al, the seg-
ments of the internal carotid artery are as follows: C1, cervical segment
carotid bulb and the ascending cervical segment (Figure (cervical portion); C2, petrous segment; C3, lacerum segment (C2 and
5-4). The carotid bulb is the most proximal aspect of the C3 comprise the commonly used petrous portion); C4, cavernous seg-
cervical ICA, forming a significant dilatation (normal ment (cavernous portion); C5, clinoid segment (not identified in some
diameter 7.5 mm vs 7.0 mm for the common carotid earlier classifications); C6, ophthalmic, or supraclinoid, segment; C7,
communicating, or terminal, segment. (From Bouthillier A, van Lov-
artery and 4.7 mm for the ICA distal to the bulb). The eren HR, Keller JT. Segments of the internal carotid artery: a new clas-
distribution of blood flow between the ICA and ECA sification. Neurosurgery 1996;38:425-432; discussion 432-423.)
occurs in a ratio of 70:30. In the ascending segment,
the ICA courses cephalad within the carotid space, a
fascially defined sheath extending from the mediasti- ECA branches arising separately from this main trunk)
num to the skull base. Apart from the ICA, the contents are rare anomalies. Anomalous ICA branches include
of the carotid space include the internal jugular vein, vessels that normally originate from the ECA, such as
lymph nodes, sympathetic nerves, and lower cranial ascending pharyngeal artery, other ICA segments (vidian
nerves IX–XII. This segment usually does not give rise artery), or the vertebrobasilar circulation (e.g., ­cerebellar
to any branches. The ICA initially lies behind and lat- arteries).
eral to the ECA, but, as it ascends, it crosses behind and During fetal development, transient segmental
courses anteromedially to the main ECA trunk (Figure ­anastomoses exist between the primitive carotid and
5-4). Normal variants include a medial origin of the ICA hindbrain circulations. If these connections fail to
(8%–15%) resulting in a superimposed appearance of obliterate, they can persist into adulthood as so-called
the ICA and ECA on the standard lateral projection. If carotid–basilar anastomoses, which are named according
tortuous, this medially projecting ICA can present clini- to the cranial nerves they parallel, for example, persis-
cally as a retropharyngeal mass. Tortuosity and even tent hypoglossal artery (Figure 5-7 and Table 5-1). Most
complete looping of the cervical ICA can occur both reported examples of persistent carotid–basilar anas-
in young children and older adults (5%–15%) unre- tomosis are found incidentally at angiography or on
lated to hypertension. True agenesis of the ICA is very cross-sectional imaging modalities. In the cervical ICA,
rare (0.01%), whereas hypoplasia of the ICA has been a persistent hypoglossal artery is the most commonly
reported to occur both as an isolated anomaly and in encountered carotid–basilar anastomosis (0.027%–
conjunction with other abnormalities (e.g., basal telan- 0.26%) that arises usually at the C1–2 level and curves
giectasia). Both anomalies are associated with a small posteromedially toward an enlarged hypoglossal canal
or absent bony carotid canal. Focal/segmental ICA nar- (Figure 5-8).
rowing is more often acquired (e.g., due to reduced
flow, dissecting aneurysm, fibromuscular dysplasia, or C2 (Petrous) ICA
segmental stenosis). Duplications and fenestrations of The C2 segment enters the skull base at the carotid canal
the extracranial ICA and a nonbifurcating carotid artery and is contained throughout its course by the petrous
(common carotid artery extends to the skull base, with temporal bone. It is subdivided into the ­ascending
 Chapter 5 Diagnostic Angiography 219

SECTION II
A B

C
Figure 5-6 Normal selective internal carotid artery (ICA) angiograms in different patients demonstrating the ICA segments. Circles indicate
positions of exocranial and endocranial openings of the petrous carotid canal. White lines denote approximate position of petrolingual ligament.
A: ICA angiogram, lateral view. Black arrow indicates genu of petrous ICA segment; white arrow indicates posterior genu of cavernous ICA; black
arrowhead indicates anterior genu of cavernous ICA; white arrowheads point to typical vascular choroid blush of the eye globe. A funnel-shaped
infundibular origin of the posterior communicating artery is shown. B: ICA angiogram, anteroposterior view. Large white arrow indicates genu of
petrous ICA segment. The S-shaped carotid siphon is not visualized due to an overlap of the distal cavernous, interdural or clinoid (C5), and proxi-
mal supraclinoid (C6) ICA segments. The origin of the ophthalmic artery (white arrowheads) is not depicted. The medially orientated ophthalmic
artery branches are visualized: the anterior falx artery, which is an extraorbital meningeal branch (small white arrow), and the anterior ethmoid
arteries (black arrowhead). The anterior choroidal artery (small black arrows), which originates from the C7 ICA segment, shows its characteristic
course overlapped by multiple perforating M1 and A1 branches. C: Slightly oblique lateral view (Haughton view) of a selective ICA angiogram
opens the carotid siphon and enables excellent visualization of its segments and their branching vessels. The ophthalmic artery is indicated by the
large white arrow. A medium-sized posterior communicating artery (small black arrows) fills the normal-sized P2 segment of the posterior cerebral
artery (small white arrow). Small white arrowheads point to a smaller-caliber anterior choroidal artery.
220 Section II  Procedures

PCOMM Table 5-1 Carotid–Basilar Anastomoses

Angiographic Find-
Embryonic Anatomy ings and Variants
Posterior com- From caudal division Variants
Trigeminal municating of primitive ICA to Fetal origin of
Otic artery developing vertebro- ­posterior cerebral
basilar circulation artery
Partially regresses Infundibular origin
Proatlantal
Hypoglossal from ICA
Primitive From cavernous ICA Most common
trigeminal to embryonic dorsal persistent embryonic
artery longitudinal neural carotid–basilar anas-
arteries tomosis
Normally regresses
ICA completely
Persistent otic From petrous ICA Extremely rare
artery to embryonic dorsal Almost never identi-
Vertebral artery longitudinal neural fied angiographically
arteries
Normally regresses
completely
Figure 5-7 Different persistent fetal carotid–vertebrobasilar anas-
tomoses. ICA, Internal carotid artery; PCOMM, posterior communi- Persistent From cervical ICA Second most com-
cating artery. (Redrawn from Luh GY, Dean BL, Tomsick TA, Wallace hypoglossal to embryonic dorsal mon persistent
RC. The persistent fetal carotid-vertebrobasilar anastomoses. AJR Am J artery longitudinal neural embryonic carotid–
Roentgenol 1999;172:1427-1432.) arteries basilar anastomosis
Normally regresses Origin from C1–2
completely level of cervical ICA
Passes through
(vertical) and horizontal portions. The short 1-cm enlarged
hypoglossal(anterior
vertical segment angles sharply at the knee (“genu”), condyloid) canal
which is angiographically easily identified. The hori-
zontal segment courses anteromedially toward the Proatlantal From cervical ICA Origin from C2–3
intersegmental to embryonic dorsal level of cervical
petrous apex. The intrapetrous ICA has two small and artery longitudinal neural ICA
inconstant branches: the vidian and caroticotympanic arteries Lower origin and
artery. Both branches may provide collateral blood Normally regresses more vertical course
flow from the ECA if ICA occlusion occurs. The vidian completely compared with per-
artery passes anteroinferiorly through the vidian (ptery- sistent ­hypoglossal
artery
goid) canal and anastomoses with ECA branches. The Horizontal suboc-
­caroticotympanic artery supplies the middle ear cavity cipital course along
and anastomoses with the inferior tympanic artery, a C1 ring
small branch from the ascending pharyngeal artery. An Occasionally arises
aberrant petrous ICA is an important anomaly that tra- from external carotid
verses the middle ear cavity and presents clinically as a artery (less common
retrotympanic mass (Figure 5-9). Noninvasive diagno- type)
sis of this important anomaly is established with MRA Adapted from Osborn AG: Diagnostic Cerebral Angiography. Lippincott ­Williams
or CTA. Failure to recognize an aberrant ICA may result & Wilkins, 1999.
in serious complications if it is mistaken for a vascular ICA, Internal carotid artery.
middle ear neoplasm. Rare anomalies include persis-
tent otic artery and persistent stapedial artery. The latter C4 (Cavernous) ICA
usually is not visualized at angiography. It arises from This segment courses within the cavernous sinus, sur-
the vertical petrous ICA segment, crosses the footplate rounded by venous channels, and can be divided into
of the stapes, enlarges the facial nerve canal en route to three subsegments: a posterior ascending or vertical
the middle cranial fossa, and terminates in the middle portion, a longer horizontal segment, and a short ante-
meningeal artery (Figure 5-10). rior vertical portion. The two vertical subsegments form
gently rounded curves called the posterior genu and the
C3 (Lacerum) ICA anterior genu. The C4 segment exits the cavernous sinus
From the end of the petrous canal, the lacerum seg- through a dural ring in the superior wall medial to the
ment of the ICA courses above the cartilage-filled fora- anterior clinoid process (Figure 5-11). The C4 segment
men lacerum. It then ascends in a posterior extension has several small but important branches that are named
of the carotid sulcus, part of the basisphenoid. The according to their topographic origins; their divisions are
lacerum segment ends at the petrolingual ligament, a named according to the territories they supply. The pos-
small reflection of periosteum between the lingula of terior trunk (meningohypophyseal artery) arises from
the sphenoid bone anteriorly and the petrous apex pos- the superior aspect of the posterior genu and supplies
teriorly. This ICA segment has no branches. branches to the pituitary gland (inferior ­hypophyseal
 Chapter 5 Diagnostic Angiography 221

SECTION II
A B
Figure 5-8 A: Preoperative left carotid angiogram, oblique view, showing the persistent primitive hypoglossal artery originating from the
internal carotid artery (ICA) at the C2 cervical level. B: Preoperative selective angiogram of the persistent primitive hypoglossal artery (PPHA),
anteroposterior view, demonstrating a saccular aneurysm at the junction of the PPHA and the posterior inferior cerebellar artery (PICA). (From
Huynh-Le P, Matsushima T, Muratani H, Hikita T, Hirokawa E. Persistent primitive hypoglossal artery associated with proximal posterior inferior
cerebellar artery aneurysm. Surg Neurol 2004;62:546-551; discussion 551.)

artery), tentorium (marginal tentorial artery), and cli- patency of the posterior communicating arteries. Rarely,
vus (clival branches) (Figure 5-12). The lateral trunk, aneurysms or direct AVFs to the cavernous sinus (trigem-
also called the inferolateral trunk, originates from the ino-cavernous fistulae) are found to arise from persistent
lateral aspect of the horizontal portion (found in 66%– trigeminal arteries.
84%) and crosses the abducens (VI) nerve within the
cavernous sinus (Figure 5-13). It supplies branches to C5 (Clinoid) ICA
cranial nerves III, IV, and VI as well as to the gasserian The C5 segment is the shortest of all ICA segments. It
ganglion and the cavernous sinus dura. The inferolateral comprises only a small, wedge-shaped area along the
trunk has important anteroinferior anastomoses with superior aspect of the anterior cavernous carotid genu
the maxillary artery through the artery of the foramen (Figure 5-6). It is an interdural segment that starts at the
rotundum. A posterior branch supplies the cavernous proximal dural ring and ends at the distal dural ring,
sinus wall, the gasserian ganglion, and the tentorium where the ICA enters the subarachnoid space. This seg-
(tentorial branch). It anastomoses with branches of the ment has no branches; only in rare instances does the
middle meningeal artery (through the foramen spino- OA arise from the C5 segment.
sum) and the maxillary artery (through the artery of
the foramen ovale). Inconstant medial branches (28%) C6 (Ophthalmic) ICA
supply the pituitary gland. Normal variants include From its junction with the clinoid segment the ICA curves
a tortuous cavernous ICA and a medial course of the upward and backward to complete the so-called angio-
C4 segment within the sella turcica instead of laterally graphic carotid siphon, an S-shaped curve that is formed
along the carotid sulcus. These so-called kissing ICAs by the cavernous and supraclinoid ICA segments. This
pose a potential hazard for transsphenoidal surgical segment is best visualized on lateral angiograms, as on
approaches to the sella turcica. AP views there is often an overlap of the distal intracav-
A persistent trigeminal artery is the most common ernous and proximal intradural ICA segments (Figure
and cephalad of the carotid–basilar anastomoses (Figure 5-6). The absence of a reliable angiographic landmark
5-14). It is found in 0.02% to 0.6% of cerebral angio- makes if difficult to distinguish between the end of C5
grams. This vessel anastomosis arises from the posterior (interdural) and the beginning of C6 (intradural) seg-
genu of C4 and follows either a parasellar (lateral) or ments. Practically speaking, lesions such as aneurysms
an intrasellar (medial) course. The lateral variant fol- that are above the OA level usually are at least partially
lows the trigeminal nerve around the dorsum sellae. The intradural. In this region a loosely adherent, angio-
intrasellar variant passes directly posterior through the graphically occult dural evagination called the carotid
dorsum sellae. Further variants of the persistent trigemi- cave is often seen adjacent to the C6 segment. Aneu-
nal artery have been described in relation to their sup- rysms occurring at this location, referred to as carotid
ply of the vertebrobasilar system, which depends on the cave aneurysms, may rupture into the subarachnoid
222 Section II  Procedures

A B

C D
Figure 5-9 Left common carotid artery (CCA) angiograms, anteroposterior (AP) and lateral views (A, B), and left internal carotid artery (ICA)
angiograms, AP and lateral views (C, D), demonstrating typical findings of an aberrant petrous ICA. Instead of a normal ICA, an enlarged inferior
tympanic artery anastomosing with a hypertrophied caroticotympanic artery is demonstrated on the CCA injection. In this aberrant arrangement,
the ascending pharyngeal artery branch of the external carotid artery gives rise to the inferior tympanic artery, which anastomoses with the caroti-
cotympanic artery to supply the normally located horizontal petrous ICA. The aberrant anastomosis is positioned posteriorly and laterally from the
ICA’s normal location. An area of narrowing and angulation is demonstrated where the aberrant segment reaches the middle ear. (From Knox WJ,
Milburn JM, Dawson R. Bilateral aberrant internal carotid arteries: treatment of a hemorrhagic complication. Am J Otolaryngol 2007;28:212-217.)
 Chapter 5 Diagnostic Angiography 223

SECTION II
A B

C D
Figure 5-10 A 14-year-old boy with headache, vomiting, dizziness, and ringing in the ear. A: Axial computed tomographic (CT) scan showing
a normal right foramen spinosum (arrow) and absence of the left foramen spinosum. B: Coronal CT scan showing the aberrant internal carotid
artery (ICA) on the left (straight arrow) and the soft-tissue density of a persistent stapedial artery (PSA) (curved arrow). C, D: Left carotid arterio-
grams, lateral and frontal views, showing a PSA arising from the aberrant ICA (arrow). (From Silbergleit R, Quint DJ, Mehta BA, Patel SC, Metes
JJ, Noujaim SE. The persistent stapedial artery. AJNR Am J Neuroradiol 2000;21:572-577.)

A CN VI
B
Figure 5-11 A: Anatomic dissection of the right cavernous sinus. The outer layer of dura has been removed from the lateral wall of Meckel cave
and the cavernous sinus. The venous plexus surrounding the nerves has been removed to expose the trigeminal divisions and cranial nerves III and
VI coursing in the wall of the cavernous sinus. The anterior clinoid process has been removed. The optic strut separates the optic canal and superior
orbital fissure. The dura extending medially off the upper surface of the anterior clinoid forms the upper dural ring around the internal carotid
artery, and the dura lining the lower margin of the clinoid extends medially to form the lower dural ring. The clinoid segment of the carotid artery,
located between the upper and lower ring, is enclosed in the dura sheath referred to as the carotid collar. B: The optic nerve has been elevated to
expose the ophthalmic artery coursing within the optic sheath. At the orbital apex, the artery penetrates the optic sheath and enters the orbital
apex on the lateral side of the optic nerve. Removal of additional optic strut exposes the mucosa lining the sphenoid sinus on the medial side. The
shortest of all the internal carotid artery segments, the clinoid segment, is exposed between the lower (proximal) and upper (distal) dural rings.
(From Rhoton AL Jr. The cavernous sinus, the cavernous venous plexus, and the carotid collar. Neurosurgery 2002;51:S375-S410.)
224 Section II  Procedures

the event of proximal ICA occlusion. A rare variant is

the ophthalmic origin of the middle meningeal artery
(0.5% of cases) that arises from the recurrent menin-
geal branch of the OA. The OA itself, on the other hand,
may anomalously originate from the middle menin-
geal artery passing into the orbit through the superior
orbital fissure or a foramen in the greater sphenoid wing
instead of through the optic canal. In 8% of cases, the
OA shows a lower, cavernous origin (Figure 5-17).
Although one or more superior hypophyseal arteries
arising from the posteromedial aspect of the C6 seg-
ment are rarely visualized, even on high-resolution digi-
tal subtraction angiography (DSA) studies, they may be
a site for aneurysm formation.

C7 (Communicating) ICA
The C7 segment begins just proximal to the origin of the
posterior communicating artery (PCoA) and ends as the
ICA bifurcates into its terminal branches, the anterior
and middle cerebral arteries (MCAs).
The first major branch, the PCoA arises from the pos-
terior aspect of the intradural ICA, courses posteriorly,
Figure 5-12 Late arterial phase of selective left internal carotid runs above the oculomotor (cranial nerve III) nerve, and
artery angiogram, lateral view, showing a prominent but normal anastomoses with the posterior cerebral artery (PCA), a
posterior pituitary blush (black arrow). The posterior trunk (so-called branch of the BA. It gives rise to several small branches,
meningohypophyseal trunk or artery) can frequently give rise to such vas- the anterior thalamoperforating arteries that supply the
cular blush, which should not be mistaken for a tumor blush. Alterna-
tively, it can be seen as a small vessel arising from the superior aspect medial thalamus and walls of the third ventricle. The
of the posterior genu. PCoA varies greatly in size (from absent to very large). If
the P1 PCA segment is hypoplastic or absent, the PCoA
may supply the entire PCA territory, which is then termed
space. ­Angiographically, this subtype of paraclinoid ICA fetal origin of the PCA. A funnel-shaped dilatation called
aneurysm arises at the anterior ICA and points medi- the PCoA infundibulum is seen at the PCoA origin in 6%
ally and superior. A more accurate way of determining to 17% of cases. It is typically round or conical shaped, 2
the location of aneurysms in the paraclinoid location mm or less in diameter, and has a wide base at its origin
(extradural vs interdural vs intradural) can be provided from the ICA. The PCoA arises from its apex (Figure 5-6,
by CTA, which enables the visualization of more reli- A). It is considered a normal variant but must be distin-
able bony landmarks (e.g., optic strut, anterior clinoid guished from an ICA–PCoA aneurysm.
process). Two important branches arise from the C6 seg- The second branch of the C7 segment is the anterior
ment: the OA and the superior hypophyseal artery. choroidal artery (AChA), which is a small but relatively
The OA is typically the first major intradural ICA constant and very important vessel (Figure 5-6, B and
branch originating from the anteromedial or supero- C). It arises from the posteromedial aspect of the C7 seg-
medial surface of the ICA near the junction of the C5/ ment a short distance above the PCoA origin either as a
C6 segments (90% intradural origin) (Figure 5-15). It single trunk or as a plexus of small vessels. The proxi-
courses superiorly, then turns and runs directly anteri- mal (cisternal) AChA segment courses posteromedially
orly through the optic canal into the orbit. Its ocular below the optic tract through the crural cistern, curves
branches include the central retinal artery (rarely visual- around the cerebral peduncle, and ends in a definite
ized) and the ciliary arteries. The vascular plexus of the lateral angulation where the AChA enters the temporal
ocular choroid can almost always identified as a distinct horn through the choroidal fissure (angiographic plexal
crescent-shaped vascular blush on midarterial phase point). The distal (intraventricular) AChA segment con-
views of ICA angiograms (Figures 5-6, A, and 5-15, B). tinues posteriorly within the supracornual cleft of the
A prominent meningeal branch, the anterior falx artery, temporal horn following the choroid plexus, typically
arises from the anterior ethmoidal branches of the OA, curving around the pulvinar of the thalamus and then
following a relatively straight course then curving superi- running anteriorly for a variable distance. The choroid
orly to supply part of the falx (Figure 5-16). Major orbital plexus of the lateral ventricle may appear as a dense
branches are the lacrimal artery and unnamed muscular homogeneous stain or blush persisting well into the
branches that supply the extraocular muscles. A number capillary or early venous phase of carotid angiograms.
of extraorbital branches arise from the OA: supraorbital, The AChA territory is variable but may include
anterior and posterior ethmoidal, dorsal nasal, palpe- many important structures in an arc-shaped zone lying
bral, medial frontal, and supratrochlear arteries, which between the corpus striatum anterolaterally and the
have extensive anastomoses with branches of the ECA. thalamus posteromedially: the optic tract, posterior
These anastomoses may become an important source of limb of the internal capsule, cerebral peduncle, cho-
collateral blood flow to the intracranial circulation in roid plexus, and medial temporal lobe. The AChA exists
 Chapter 5 Diagnostic Angiography 225

SECTION II
A B

C D
Figure 5-13 Right internal carotid artery angiogram, lateral view. A: Enlarged inferolateral trunk (ILT, small black arrow) originating from hori-
zontal portion of the cavernous (C4) internal carotid artery (ICA), which has formed a dural arteriovenous fistula (DAVF, white arrowheads) with
drainage into the superior petrosal sinus (large black arrow). Subsequent anterograde venous drainage is shown into the sigmoid sinus. B: Superse-
lective angiogram, lateral view, obtained from microcatheter injection into right ILT (small black arrow) better illustrates the fine fistulous network
of dural vessels (white arrowheads) that shunt into superior petrosal sinus (large black arrow) as well as retrogradely into the posterior portion of
the cavernous sinus (black arrowhead). Left vertebral angiogram, oblique Waters view, early arterial (C) and subsequent later arterial (D) phases
showing further arterial supply to DAVF from enlarged right lateral pontine artery (small black arrow) with numerous fistulous connections (white
arrowheads) to draining superior petrosal sinus (large black arrow). At the origin of this arterial feeder from the basilar artery a posteriorly directed
flow-related aneurysm is disclosed (black arrowhead). (Courtesy Dr. William McAuliffe, Perth.)
226 Section II  Procedures

A B
Figure 5-14 A: Left internal carotid artery (ICA) angiogram, anteroposterior view, showing an abrupt termination of the contrast column in the
mid-M1 portion of the left middle cerebral artery (MCA) consistent with an occlusion. A meniscus of contrast outlines the proximal clot (large black
arrow). The lateral lenticulostriate arteries arising from the proximal M1 segment show normal opacification, but there is no filling of branches
beyond the thrombus. This acute thromboembolic arterial occlusion complicated endovascular treatment of a ruptured anterior communicating
artery aneurysm (large white arrow). A persistent trigeminal artery that arises from the left cavernous ICA portion and contributes to the basilar artery
circulation is also identified (small black arrow). B: Left common carotid artery angiogram, lateral view, showing large bare area in the MCA distribu-
tion only with filling of the posterior M2 division (black arrowheads). This injection was performed after partial coil embolization of the ruptured
anterior communicating artery aneurysm (large white arrow) had been achieved and subsequent intraarterial thrombolysis of the M1 occlusion had
been initiated. In addition, a persistent trigeminal artery with a typical appearance arising from the cavernous ICA is disclosed (small black arrow).

A B
Figure 5-15 A: Selective internal carotid artery angiogram, lateral view, of a the ophthalmic artery (OA) and its branches. White arrow indicates
the abrupt angulation where the OA passes up and over the optic nerve. 1, OA; 2, ocular OA branches (black arrowheads indicate faint vascular
choroid blush); 3, orbital OA branches; 4, lacrimal artery; 5, anterior ethmoid arteries. B: Midarterial phase of an ICA angiogram, lateral oblique
view, showing the characteristic crescent-shaped appearance of vascular choroid blush (black arrowheads), which is caused by contrast filling of the
ocular vascular choroid plexus. This sign should be actively looked for when performing endovascular embolization procedures in branches of
the external carotid artery because the sign may indicate a potential hazard.
 Chapter 5 Diagnostic Angiography 227

in hemodynamic balance with the posterolateral and the AChA is seen in only 3% of cerebral angiograms. In

SECTION II
medial posterior choroidal arteries (PCA branches). rare cases, the AChA originates from the ICA proximal to
Branches of the AChA anastomose freely and frequently the PCoA (instead of distal). This uncommon anomaly
with these vessels, resulting in a considerable variation needs to be considered preoperatively if a PCoA may be
in size and vascular territory of the AChA. Hypoplasia of occluded for aneurysm treatment.

Vertebrobasilar System
With minor exceptions, the entire blood supply of the
medulla, pons, midbrain, and cerebellum is derived from
the vertebrobasilar system. Familiarity with its develop-
ment, gross anatomy, normal imaging appearance, and
vascular territory is a prerequisite for understanding
pathologic processes affecting the posterior circulation.

Vertebral Arteries
What Are the Anatomic Segments, Common
Variants, and Branches of the Vertebral Arteries?
The VA can be divided into four segments:
1. The V1 (extraosseous) segments extend from the ori-
gin of the VAs on the subclavian artery posterosu-
periorly to enter the transverse foramen of the sixth
cervical vertebrae.
2. The V2 (foraminal) segments ascend vertically pass-
ing through the foramina of the C3–6 transverse
processes, followed by an inverted L-shaped course
through C2. After exiting from the axis, the VAs turn
again, running superiorly through the C1 transverse
Figure 5-16 Internal carotid artery angiogram, lateral view, of the foramen (Figure 5-18).
ophthalmic artery (large white arrow) and its orbital and extraorbital
branches. Black arrowheads delineate a prominent anterior falx artery. 3. The V3 (extraspinal) segments begin where the VAs
This is an extraorbital dural branch that supplies the anterior portions exit from C1 to follow a sharp posteromedial bend
of the falx cerebri. Other extraorbital branches include the anterior around the atlantooccipital articulation, producing a
ethmoid arteries (white arrowhead). Another important orbital branch prominent grooving along the posterior ring of C1.
is the lacrimal artery (small black arrow), which gives rise to the recur-
rent meningeal artery (small white arrows). This dural branch courses
It then turns sharply forward and upward to pierce
backward through the superior orbital fissure to anastomose with the dura at the level of the foramen magnum.
branches of the middle meningeal artery.

A B
Figure 5-17 Lateral oblique (A) and anteroposterior oblique (B) views of an internal carotid artery (ICA) angiogram demonstrating an anoma-
lous origin of the ophthalmic artery (small black arrows) inferiorly from the cavernous ICA segment. In addition, a large, loculated anterior com-
municating artery aneurysm (large black arrows) is noted. The wide-necked aneurysm shows a prominent inferiorly pointing second locule (white
arrow) that arises from the primary sac. (Courtesy Dr. Tejinder Pal Singh, Perth.)
228 Section II  Procedures

­perforating arteries, and the PICA. The posterior spinal

artery arises from the distal VA or PICA. It descends
downward along the dorsal surface of the medulla and
spinal cord, forming a vascular network together with
numerous spinal radicular branches along the cord all
the way down to the cauda equina. The anterior spinal
artery arises from the distal VA and courses inferome-
dially to unite with its counterpart from the opposite
VA in 50% of cases (Figure 5-19). It gives off a num-
ber of small perforating branches to supply the anterior
medulla running caudad in the anteromedian sulcus of
the spinal cord. The small perforating arteries arise directly
from the VA to supply the olive and inferior cerebellar
peduncle. The PICA is the most important, largest, and
most variable of all the cerebellar arteries. It arises from
the VA at the anterolateral aspect of the brainstem, near
the inferior olive. As it courses around the medulla,
the main PICA trunk can be divided in four segments
and two distinct loops, which are generally best visual-
ized on the lateral projection of a vertebral angiogram
­(Figure 5-21). It terminates distal the apex of the distal
loop by dividing into tonsillohemispheric (lateral) and
Figure 5-18 Right vertebral angiogram, lateral view, showing the vermian (medial) branches.
V2 (foraminal), V3 (extraspinal), and V4 (intradural segments). The In approximately 75% of patients, the left VA is the
vertebral artery (VA) shows a nearly vertical course as it passes through same size or larger than the right. However, when the left
the transverse foramina of the C6 to C3 vertebrae. Numerous segmen- VA arises directly from the aortic arch (5%–6% of cases),
tal muscular branches are indicated (small white arrows). The vertebral
canal of C2 is indicated by the lower two white dotted circles. The VA runs it usually is smaller and may terminate intracranially as
superiorly then turns laterally within C2, forming an inverted L (white the ipsilateral PICA. A shared anterior inferior cerebellar
arrowhead). After exiting C2, the VA turns cephalad to pass through the artery (AICA)–PICA trunk is a common normal variant.
transverse foramen of C1 (upper white dotted circle). As it exits the trans- Occasionally a single trunk supplies both PICAs with a
verse foramen of C1 it curves around the atlantooccipital articulation,
turning sharply backward and medially along the upper border of the
midline crossing anastomotic segment (Figure 5-22).
posterior ring of the atlas. It then bends forward in a tight hairpin In 0.2% of cases, a small VA terminates in a PICA, and
turn (black arrow) to pierce the dura as it passes through the foramen the opposite VA provides most of the posterior fossa
magnum (black dotted circle). The posterior inferior cerebellar artery is blood supply. An extradural origin of PICA is another
indicated by the black arrowhead. normal variant (5%–18%) where the PICA origin from
the VA lies below the foramen magnum. In one third of
4. The intradural V4 segments first course antero- cases, the caudal PICA loop extends below the foramen
medially through the foramen magnum and then magnum with a normal intradural origin. A duplicated
­superomedially behind the clivus to unite at or near PICA is a rare normal variant (2%). A PICA origin from
the pontomedullary junction. the posterior meningeal artery or the ICA or a posterior
Each VA has cervical, meningeal, and intracranial meningeal artery origin from PICA instead of the VA has
branches. been described as an uncommon anomaly. Both a bifid
The vascular supply to the neck is organized segmen- and a duplicate VA origin and fenestrated VAs are rare
tally according to intervertebral level. Each cervical level anomalies, found in less than 1% of anatomic dissec-
is supplied by branches from both the vertebral and the tions (Figure 5-19). The latter is often associated with
external carotid arteries. The VAs give rise to muscular and other anomalies of the brain and spine (e.g., fused ver-
spinal cervical branches. Each V2 segment gives off multi- tebrae, aneurysms, and vascular malformations).
ple small unnamed muscular branches that supply the deep Numerous anastomoses exist between muscular
cervical musculature. Segmental spinal branches ­(Figure extracranial VA branches and ECA branches (e.g., from
5-19) supply the spinal cord and its coverings, anasto- the occipital and ascending pharyngeal arteries) and may
mosing with spinal arteries from other vessels such as the provide an important source of collateral flow in occlu-
ascending pharyngeal artery and the thyrocervical trunk. sive vascular disease. These anastomoses are regarded as
The meningeal branches supply part of the posterior potentially dangerous vessels when endovascular embo-
fossa dura. The anterior meningeal artery arises from the dis- lization procedures from the ECA system are performed.
tal portion of the V2 segment. This vessel usually is very
small and supplies only the dura around the foramen mag- Basilar Artery
num. The posterior meningeal artery originates just below
the foramen magnum and follows a ­relatively straight What Are the Branches of the BA and Its
superomedial course to supply the falx cerebelli and the Common Variants?
dura along the medial occipital bone (Figure 5-20). The BA is a large midline or paramedian vessel that
Intracranial VA branches include small meningeal extends from its origin anterior to the pons near the
branches, the posterior and anterior spinal arteries, pontomedullary junction to its terminal bifurcation
 Chapter 5 Diagnostic Angiography 229

SECTION II
A B

C D
Figure 5-19 A: Right vertebral artery angiogram, Waters anteroposterior view, showing a fenestration of the proximal intradural (V4) segment
of the right vertebral artery (VA) (small black arrows). The right V4 segment is mildly hypoplastic, and there is minimal reflux into the distal left VA
present at the vertebrobasilar junction. There is an unusual high origin of the right posterior inferior cerebellar artery (PICA) (large black arrow)
from the proximal basilar artery just below the origin of the anterior inferior cerebellar arteries (white arrowheads) as a normal variation. B: Same VA
angiogram, lateral view, confirms the fenestrated proximal V4 segment of the vertebral artery (small black arrows). The anterior spinal artery (white
arrowheads) is depicted as a small almost vertically orientated vessel coursing downwards through along the anterior aspect of the cervical cord.
Prominent muscular branches originating from the hairpin turn at the C1 level are also shown (large black arrow). A small segmental spinal branch
is depicted originating from the V2 segment (black arrowhead). The right PICA originates unusually high from the basilar artery (small white arrows)
and shows a classical double loop-shaped course. C: Left vertebral angiogram, lateral view, of the same patient showing the left dominant VA (white
arrowheads). Both PICAs, on the right side (small white arrows) originating from the lower basilar artery and on the left side (small black arrows) with a
normally located origin from the intradural VA, are depicted. A small aneurysm (large black arrow) that arises from the left PICA origin is demonstrated.
D: Left vertebral angiogram, Towne anteroposterior projection, showing the posterior cerebral arteries and their major branches. 1, Thalamoperforating
arteries (small midline blush); 2, P1 segment; 3, P2 segment; 4, posterior temporal artery; 5, P3 segment; 6, parietooccipital artery; 7, calcarine artery.
230 Section II  Procedures

into the two PCAs. It is located in the interpeduncular

cistern adjacent to the dorsum sellae or in the supra-
sellar cistern below the floor of the third ventricle. The
normal BA is 3 to 4 mm in diameter and averages 32
mm in length. Branches of the BA comprise labyrin-
thine (internal auditory), perforating, and cerebellar
arteries and the PCAs. The labyrinthine arteries are long
slender vessels that arise either directly from the BA
(16%) or from the superior (25%) or anterior infe-
rior (45%) cerebellar arteries. They accompany cranial
nerves VII and VIII into the internal acoustic meatus.
Along its course in the prepontine cistern the BA gives
off numerous pontine perforating arteries, which can be
divided into median and paramedian pontine perforat-
ing arteries and lateral or circumferential pontine arteries
(Figure 5-21).
The BA gives rise to two important cerebellar arteries:
the AICA and the superior cerebellar artery (SCA).
The AICAs are the smallest of the three cerebellar
arteries that arise as single (72%), duplicate (26%),
or triplicate (2%) vessels from the proximal BA. They
course directly laterally into the cerebellopontine
Figure 5-20 Left vertebral artery angiogram, lateral view, showing a angle cistern lying ventral and medial to cranial nerves
prominent posterior meningeal artery (black arrowheads) as a normal VII and VIII. In two thirds of cases, the AICA shows
variant. This dural vessel arises just below the level of the foramen an outward loop that curves into the internal acous-
magnum from the posterior bend of the V3 segment and runs in a tic meatus that has a characteristic single or double
relatively characteristic course superomedially along the medial aspect
of the occipital bone to supply the occipital dura and the falx cerebelli. (N or M shaped) curve on the lateral angiogram (Fig-
The left posterior inferior cerebellar artery (small white arrows) and low ure 5-2, C). It terminates by running over the cerebel-
originating anterior inferior cerebellar artery (white arrowhead) are lum to supply its petrosal (anterolateral) surface. The
depicted as branches of the V4 segment (large white arrow) of the left size of the AICA has a reciprocal relationship with that
vertebral artery. Reflux into the contralateral right V4 segment is also
demonstrated (small black arrow).
of the PICA, and both arteries may share a common
origin, and their hemispheric branches have numer-
ous anastomoses.
The SCAs are the most constant and rostral infraten-
torial BA branches arising just prior to the BA termina-
tion (Figures 5-2 and 5-22). Duplicate (8%) and even
triplicate (2%) vessels have been identified as normal
variants. In their proximal course, they are separated
from the PCAs by cranial nerve III. In their course
sweeping around the cerebral peduncles, they lie below
cranial nerve IV and above the trigeminal nerve. On
AP Towne views they seem to approximate each other
behind the brainstem. The superior vermian branches
appear very close to the distal PCA on lateral views.
The hemispheric SCA branches ramify over the tento-
rial surface of the cerebellum (Figure 5-2). The vascular
territory of the AICA includes the superior surface of
the cerebellar hemisphere, superior cerebellar pedun-
cle, upper vermis, dentate nucleus, and part of the bra-
chium pontis.
Numerous anastomoses among the PICA, AICA, and
SCA exist over the cerebellar hemispheres and vermis
(Figure 5-22).
The perforating arterial supply to the medulla, pons,
and tegmentum shows significant variations. The lateral
Figure 5-21 Arterial phase of a left vertebral angiogram, lateral medulla is supplied by the V4 VA segments and the cen-
view, showing the posterior inferior cerebellar artery (PICA) with its tral medulla by perforating BA branches. Except for its
distinct segments and some of its branches. Reflux into the right VA upper parts (small SCA branches), the pons is supplied
is also demonstrated. 1, Anterior medullary segment of PICA; 2, lat- by perforating branches from the BA. The tegmentum
eral medullary segment of PICA (caudal loop); 3, posterior medullary
segment; 4, cranial loop of PICA; 5, supratonsillar segment of PICA;
typically is supplied by branches of the PCAs and SCAs,
6, hemispheric and vermian branches of PICA; 7, prominent lateral but it also receives contribution from perforating arter-
pontine artery. ies directly from the BA.
 Chapter 5 Diagnostic Angiography 231

SECTION II
A B

C D
Figure 5-22 A: Angiogram of the right vertebral artery, anteroposterior (AP) view. Bilateral supply of the posterior inferior cerebellar artery
(PICA) from the right vertebral artery is demonstrated. The intradural portion of the right vertebral artery terminates in a very prominent right
PICA (small black arrows). The cranial loop of the right PICA gives rise to a very prominent midline-crossing bridging segment (large black arrow).
This segment then forms the contralateral cranial loop of the left PICA, which divides into its vermian (medial) branches and tonsillohemispheric
(lateral) branches (white arrow). B: Left vertebral artery angiogram, AP view. No supply of the left PICA from the injected left vertebral artery (white
arrow) is noted. No reflux into a distal intradural portion of the contralateral vessel is shown, confirming the PICA terminating variant of the right
vertebral artery. The basilar artery shows normal supply to the anterior inferior (large black arrows) and superior (small black arrows) cerebellar arter-
ies. C: Right vertebral artery angiogram, lateral view. The V4 (intradural) segment of the right vertebral artery gives rise to a prominent right PICA.
The anterior medullary segment, the caudal loop (arrowhead), and posterior medullary segment are nonduplicates. The right supratonsillar PICA
segment gives rise to the short interconnecting segment (white arrow) with the left PICA, which is depicted en face. The cranial loops are formed
as duplicate vessels (large black arrows), giving rise to the terminal PICA branches bilaterally. Note two prominent muscular branches originating
from the extradural V3 portion of the right vertebral artery (small black arrows). D: Left vertebral artery angiogram, lateral view. No direct PICA
supply is demonstrated. The anterior inferior cerebellar arteries are depicted in normal location bilaterally (small black arrows). A very prominent
left superior cerebellar artery (large black arrows) gives rise to a small collateral hemispheric branch to the territory of the PICA (white arrows).
(Courtesy Dr. William McAuliffe, Perth.)
232 Section II  Procedures

A B
Figure 5-23 A: Left vertebral angiogram, oblique view, showing a fenestrated basilar artery (large black arrow). A typical aneurysm is present at
the proximal end of the fenestration (small black arrow). B: Computed tomographic angiography with targeted, angled anteroposterior, thick maxi-
mum intensity projected view allows visualization of the fenestrated basilar artery. Overlying bony structures do not permit complete evaluation
of the arterial segments and associated aneurysm on a single reconstructed view. Both proximal intradural portions (V4) of the vertebral arteries
(white arrowheads) and the fenestrated basilar artery are visualized. (Courtesy Dr. William McAuliffe, Perth.)

If a fetal-type PCA is present, this vessel is not opaci- rarely seen on a single angiogram (e.g., when three of
fied when the posterior circulation is studied. In bilat- the four major brain supplying arteries are occluded),
eral cases, the BA terminates by bifurcating into the but its components usually are visualized sequentially.
SCAs. Common anomalies of the BA are fenestrations The anatomic integrity of the circle of Willis can be
(1.3%) or duplications, which are the result of failure established using cross-compression angiography. In
of fusion of the embryonic plexiform primitive longi- this technique, a carotid artery is manually compressed
tudinal neural arteries. These are commonly associated while the contralateral carotid or a VA is injected. This
with an aneurysm at the proximal end of a fenestration information is particularly relevant when deconstruc-
(Figure 5-23). Rarely, the cerebellar arteries arise from tive neurosurgical or endovascular procedures such as
the VA, the cavernous ICA, or the PCAs. carotid sacrifice in the treatment of, for example, giant
cavernous aneurysms or life-threatening epistaxis are
Circle of Willis being contemplated.
The anterior cranial arterial circulation represents
What Structures Define the Most Important the paired terminal ICAs and their terminal branches:
Collateral Pathway at the Base of the Brain, the ACAs and the MCAs. The proximal ACA segments,
and What Are the Common Variants? which are also called precommunicating or A1 segments,
The circle of Willis is an anastomotic ring at the base are part of the circle of Willis. The ACoA, which lies at
of the brain providing collateral pathways between the the anterior end of the interhemispheric fissure, inter-
proximal major cerebral arteries. This structure is subject connects both A1 segments. The A1 segment is best
to great individual variation; it is present in its complete visualized on AP or submentovertex views. Because the
or unbroken form in 52% of cases. A complete circle of ACoA typically is orientated in an oblique (rather than
Willis consists of two ICAs, two anterior cerebral arter- strictly anteroposterior) plane, oblique, Waters, or sub-
ies (ACAs; A1 segments), the anterior communicating mentovertex views may be required to demonstrate this
artery (ACoA), two PCoAs, the BA, and two PCAs (P1 vessel clearly without the presence of overlapping ves-
segments) (Figure 5-24). Anatomically the circle of Wil- sels (Figure 5-25). Temporary cross compression of the
lis lies above the sella turcica within the interpeduncular contralateral carotid artery is sometimes necessary to
and suprasellar cisterns. It surrounds the ventral surface demonstrate the ACoA.
of the diencephalon and lies adjacent to the optic nerves The posterior cranial arterial circulation consists of
and tracts. It can be easily visualized using noninva- the vertebrobasilar system and the paired PCAs. The two
sive high-resolution imaging techniques such as CTA PCoAs provide the major anastomotic link between the
or three-dimensional (3D) time-of-flight (TOF) MRA. anterior (carotid) and posterior (vertebrobasilar) circula-
However, a detailed study of its small but important per- tions. Each PCoA joins the ipsilateral so-called precommu-
forating branches is still largely the domain of conven- nicating or P1 segment of the PCA to close the circle of
tional cerebral angiography. The entire circle of ­Willis is Willis. Transient reflux of contrast into the PCoA during
 Chapter 5 Diagnostic Angiography 233

Distal medial striate artery

SECTION II
Vessels dissected out: inferior view (recurrent artery of Heubner)
Anterior cerebral artery Anteromedial central (perforating)
(A 2 segment) arteries
Anterior communicating artery
Hypothalamic artery
Anterior cerebral artery
(A 1 segment)
Anterolateral central
Ophthalmic artery (lenticulostriate) arteries

Internal carotid artery

Middle cerebral artery

Superior hypophyseal artery
Posterior communicating artery Inferior hypophyseal artery

Anterior choroidal artery

Posterior cerebral artery
(P2 segment) Thalamotuberal
(P1 segment) (premammillary) artery

Posteromedial central
Superior cerebellar artery (perforating) arteries

Basilar artery Thalamoperforating artery

Pontine arteries Posteromedial central

(paramedian) arteries

Anterior inferior cerebellar artery (AICA) Labyrinthine (internal acoustic) artery

Vertebral artery

Figure 5-24 Anatomic diagram depicts the circle of Willis. Innumerable perforating branches arise from every part of the circle of Willis to
supply vital structures at the base of the brain. From Netterimages.com.

injection of either the ICA or a VA often occurs (Figure

5-2, C). Ipsilateral carotid cross compression may improve
reflux into the PCoA during a VA injection. Lateral or
submentovertex views usually best depict the PCoA anat-
omy, whereas the BA bifurcation and the P1 segments are
optimally visualized on steep Towne or shallow submen-
tovertex projections of vertebral angiograms.
Important perforating branches arise from every part
of the circle of Willis: the medial lenticulostriate arteries
and the recurrent artery of Heubner supply the caudate
nucleus head, anterior limb of the internal capsule,
and other parts of the basal ganglia. Several small per-
forating branches arise from the ACoA, which may
have a significant vascular territory including the ante-
rior hypothalamus, optic chiasm, parts of the corpus
­callosum, columns of the fornix, lamina terminalis, and
parolfactory areas. The anterior thalamoperforating arter-
ies arise from the PCoA to supply part of the thalamus,
the infralenticular limb of the internal capsule, and the
optic tracts (Figure 5-24). The distal BA and P1 segments
Figure 5-25 Left internal carotid artery angiogram, submentover- give rise to numerous perforating arteries, the posterior
tex oblique view, depicting the anterior communicating artery (small
black arrow). Note cross-flow with filling of the right anterior cerebral
thalamoperforating arteries, which course within the inter-
artery. The reflux enables depiction of both A1 segments (large black peduncular fossa to enter the brain behind the mamil-
arrows). lary bodies (Figure 5-2, C). In 42% of cases, a single
234 Section II  Procedures

A B

C D
Figure 5-26 Anteroposterior (A), lateral (B), and lateral oblique (C) views of a selective right internal carotid artery angiogram show an infero-
laterally pointing aneurysm (large white arrow) at the origin of the posterior communicating artery. Filling of the right posterior cerebral artery
(small black arrow) with temporary short reflux into the right P1 segment (black arrowhead) is demonstrated. A prominent anterior thalamoperforat-
ing artery (white arrowheads in B and C) arises from the mid-posterior communicating artery. The origin of the posterior communicating artery rela-
tive to the vascular anatomy of the aneurysm is not clearly depicted on the standard views (A, B). It appears to arise from the aneurysm sac on the
oblique working projection view for coiling (small white arrow) as demonstrated by double density sign, which projects on the aneurysmal wall (C).
Note the presence of a microcatheter within the petrous internal carotid artery portion. D: The three-dimensional rotational angiographic image
of the right internal carotid artery in the same patient better visualizes the origin of the posterior communicating artery (small white arrow) with
respect to the aneurysm sac (large white arrow) as well as the size and configuration of the aneurysm neck. (Courtesy Dr. William McAuliffe, Perth.)

posterior thalamoperforating artery, the so-called artery of 22% of cases, and hypoplastic A1 segments in 10% of
Percheron, is the largest branch arising from one P1 seg- anatomic dissections. A true aplastic A1 segment is found
ment to supply both thalami. in only 1% to 2% of cases (Figure 5-28). An absent P1
A perfect circle in which all components are present segment is very uncommon. A single ACoA is present in
and of adequate and equal size occurs in only 21% of approximately 60% of cases. Multiple vascular channels
autopsy specimens. The PCoAs usually are smaller than (plexiform ACoAs, 10%–33%) and a duplicated (18%) or
the ICAs and PCAs (Figure 5-26). Some of the more com- fenestrated (12%–21%) ACoA are considered normal vari-
mon variations include direct origin of the PCA from the ants of the ACoA. An absent ACoA occurs in only 5% of
ICAs (fetal PCA) in 20% to 30% of cases (Figure 5-27), cases. In the presence of stenoocclusive disease, such nor-
hypoplastic posterior communicating arteries in 15% to mal variations may become very significant prognostic
 Chapter 5 Diagnostic Angiography 235

SECTION II
A B

C D
Figure 5-27 Anteroposterior (A, C) and lateral (B, D) projections of a right internal carotid artery angiogram obtained before and after coil
embolization of a lobulated posterior communicating artery aneurysm (large white arrow). The narrow aneurysm neck arises directly from the pos-
terior communicating segment of the posterior cerebral artery (small white arrow), which shows a direct origin from the internal carotid artery, a so-
called fetal variant. On the control angiogram, which was obtained directly after embolization (C, D), complete obliteration of the aneurysm sac
by the coil mass (large white arrow) and preservation of the parent artery can be noted (small white arrow). (Courtesy Dr. William McAuliffe, Perth.)
236 Section II  Procedures

A B
Figure 5-28 A: Anteroposterior view of an internal carotid artery angiogram showing an absent A1 segment of the anterior cerebral artery
(ACA). Because the ACA is absent, a prominent anterior choroidal artery is seen (small black arrows). The internal carotid artery essentially termi-
nates in the M1 segment of the middle cerebral artery (large black arrow). B: Internal carotid artery angiogram of the same patient, lateral projec-
tion, showing absence of the ACA and the posterior communicating artery. The anterior choroidal artery (small black arrows) and ophthalmic artery
are depicted (large black arrow).

A B
Figure 5-29 A: Left internal carotid artery angiogram, anteroposterior projection, showing a short segmental fenestration of the A1 segment, which
is a normal variant (white arrow). The middle cerebral artery (MCA) segments and branches are indicated as follows: 1, M1 (horizontal) segment;
2, MCA bifurcation; 3, MCA genu; 4, lateral lenticulostriate arteries (penetrating M1 branches); 5, M2 segment; 6, apex of sylvian fissure (angiographic
sylvian point); 7, M3 segment; 8, M4 segment (ramifying cortical hemispheric branches). B: Caldwell oblique view best depicts the proximal segments
of the anterior cerebral artery. Thereby, the fenestrated A1 segment (black arrow) is again visualized. The anterior communicating artery is not seen.

factors, such as a small or absent PCoA that was found to in the ICA near the OA origin, a fenestration of the ACA
be an independent risk factor for ischemic cerebral infarc- (Figures 5-29 and 5-30), and an azygos ACA. The latter
tions in cases of ICA occlusion. Another example is an is a solitary, unpaired vessel that arises as a single trunk
isolated ICA, which occurs when a fetal PCA and absent from the confluence of the bilateral A1 segments with
A1 segment both are present on the same side. This setup an absent ACoA (Figure 5-31). This anomaly is found in
eliminates collateral flow from the contralateral ICA or various forms of holoprosencephaly. Rare anomalies of
the vertebrobasilar system in cases of stroke to the vascular the posterior circulation comprise persistent carotid–bas-
ICA territory, which supplies both the ipsilateral MCA and ilar anastomoses, which are described in chapter on the
PCA, potentially resulting in a major neurologic deficit. ICA (see Chapter 5, Section “Internal Carotid Arteries”).
True anomalies of the circle of Willis are rare. They A detailed discussion of the vessels distal to the circle of
include an infraoptic origin of the ACA, which is located Willis is beyond the scope of this article.
 Chapter 5 Diagnostic Angiography 237

SECTION II
A B

C D
Figure 5-30 Angiograms of different vascular territories from the same patient reveal multiple cerebral aneurysms. Towne anteroposterior pro-
jections of selective left vertebral artery angiogram at early (A) and subsequent later (B) arterial phases demonstrate a large, wide-necked aneurysm
at the tip of the basilar artery (large white arrow) that incorporates both P1 segments into its neck and intraaneurysmal flow patterns. The inflow
contrast jet enters the right paracentral orifice (A) and circulates from the right dome in clockwise fashion to the left lateral neck and into the left
P1 segment, which shows delayed contrast filling (A, B). The central part of this vortex shows slower flow with contrast stasis (asterisk in B). Due
to symptoms related to mass effect on the mesencephalon, a staged treatment of the basilar tip aneurysm was initiated, with placement of a stent
over the wide aneurysm neck. The proximal and distal markers (small black arrows) are visualized in the mid-basilar artery and the left posterior
cerebral artery, respectively. A second, very small aneurysm (small white arrow) arises from the distal basilar artery between the origin of the right
superior cerebellar artery and the right P1 segment. Lateral oblique (C) and transorbital oblique (D) projections of the right common carotid
artery angiogram show two other aneurysms at the A2/A3 junction of the right anterior cerebral artery. The larger aneurysm (large white arrow)
demonstrates a broad neck that incorporates the proximal pericallosal artery over a short distance. The other smaller aneurysm arises from the
origin of the callosomarginal artery (small black arrow). A tiny fenestration of the distal A1 segment (white arrowhead in C) is depicted. (Courtesy
Dr. Constantine Phatouros, Perth.)
238 Section II  Procedures

A B
Figure 5-31 Anteroposterior (A) and transorbital oblique (B) views of left internal carotid artery angiogram show a solitary midline trunk, a
so-called azygos anterior cerebral artery (large white arrow), which supplies both the bilateral pericallosal and the right callosomarginal arteries (small
black arrows). The right A1 segment gives rise solely to the right orbitofrontal arteries and the left callosomarginal artery (small white arrows), which
crosses the midline underneath the anterior falx cerebri. A small inferiorly directed, mildly lobulated aneurysm (large black arrow) arises from the
right A1/A2 junction at the origin of the anterior communicating artery (black arrowhead). (Courtesy Dr. Tejinder Pal Singh, Perth.)

INDICATIONS sign), and/or presence of irregular aneurysm or pseu-

doaneurysm associated with focal luminal narrowing
Aneurysms or irregularity (Figure 5-32) (see section on Intracranial
Dissection).
What Are the Characteristics of Intracranial Fusiform intradural aneurysms represent less than 1%
Aneurysms, and What Is the Best Way to Classify of intracranial aneurysms and frequently are associated
Them? with vessel tortuosity, atherosclerosis, hypertension, and
Intracranial aneurysms are classified according to their old age. They typically are located in the supraclinoid
gross pathologic appearance as saccular or “berry” aneu- ICA and the basilar trunk. They often present with symp-
rysms, fusiform aneurysms, and dissecting aneurysms. toms of mass effect, and rupture is uncommon when
Saccular aneurysms are round or lobulated focal out- the condition is mild. In large aneurysms, stagnation
pouchings that usually arise from arterial bifurcations. of blood flow may lead to thrombus and subsequent
Occasionally they originate directly from the lateral embolic stroke. If ectasia reaches bizarre proportions,
wall of a nonbranching artery. The aneurysmal sac may the terms megadolichobasilar anomaly in the BA or giant
have a narrow orifice (neck), or it may arise from a more fusiform serpentine aneurysm are used. The latter subtype
broad-based neck. Most intracranial aneurysms are true typically shows a more malign course due to recurrent
aneurysms, that is, they contain at least some layers that SAH, progressive mass effect (e.g., brainstem compres-
are normally found in the arterial wall yet lack other sion, cranial nerve palsies, or obstructive hydrocepha-
components. Acute thrombi and organized laminated lus), or embolic strokes. MRI has shown some evidence
clots are frequently present within the aneurysm lumen. that intracranial dissection may play a role in the growth
Intracranial dissecting aneurysms are caused by pen- of these lesions.
etration of circulating blood into the arterial wall with The risk of harboring an incidental intracranial aneu-
extension between its layers. The opacified false lumen rysm is 1% to 3% in autopsy series and between 1%
is contained by the vessel adventitia. Once ruptured, and 5% in the general population. The annual risk of
intracranial dissecting aneurysms have a high risk of rupture is estimated to be 1% to 2%. The reported fre-
rebleeding (up to 70%) within the first week after initial quency of multiple aneurysms in large referral centers
SAH, with a high mortality rate (46%). Differentiating ranges from 20% to 33% depending on angiographic
between dissecting aneurysms from saccular aneurysms quality, number of vessels examined, and referral pat-
is important because the treatment may differ. Angio- terns, which all influence the rate of detection of mul-
graphically, the signs of intracranial dissection may be tiple lesions. Up to 30% of patients with SAH have
subtle, including irregular tapering of the vessel lumen, multiple aneurysms. Female gender, cigarette smoking,
intraluminal linear filling defects, retention of contrast and vasculopathies such as fibromuscular dysplasia and
within the vessel wall, fusiform dilatation interrupted polycystic kidney disease are recognized risk factors for
by segments of string-like narrowing (“pearl and string” multiple ­aneurysm.
 Chapter 5 Diagnostic Angiography 239

SECTION II
A B
Figure 5-32 A: Towne anteroposterior view of left vertebral artery angiogram showing an irregular and fusiform-shaped aneurysm of the
peripheral left superior cerebellar artery (SCA; black arrow). Flash filling with streaming of the right middle cerebral artery territory via the posterior
communicating artery is also demonstrated. B: Superselective microcatheter injection of the left SCA, lateral view, better depicts the morphology
of this distal dissecting aneurysm with multiple irregular and partially flap-like, filling defects (black arrow). The hemispheric SCA branches that
arise distal to the aneurysm are clearly visualized (white arrow). (Courtesy Dr. William McAuliffe, Perth.)

Which Other Types and Causes of Intracranial rupture into the sphenoid sinus causing massive and
Aneurysms Exist? life-threatening epistaxis. Delayed clinical presenta-
Mycotic aneurysms of infectious origin account for 2% tion with stroke or hematoma is common (up to 3–4
to 4% of all intracerebral aneurysms (5%–15% in chil- weeks following the trauma). Angiographic findings in
dren) and have a high risk of rupture. They most often traumatic aneurysms commonly include peripheral or
occur in patients with infective endocarditis or a history nonbranching locations, delayed filling and emptying
of drug abuse. The most common causative bacterium of an often irregularly outlined aneurysmal cavity with
is Streptococcus viridans, and the most common fungal or without mass effect from hematoma, and absence of
agent causing aneurysms is Aspergillus fumigatus. These a definable neck.
lesions typically arise on the smaller arteries distal to Rarely, neoplastic (oncotic) aneurysms develop as
the circle of Willis and represent actual pseudoaneu- a result of either direct vascular invasion by tumor
rysms caused by distally lodged septic emboli. The lat- or implantation of distal tumor emboli (0.1% of all
ter can either directly destroy the intima or reach the aneurysms). Both primary intracranial (e.g., menin-
adventitia via vasa vasorum. The inflammation eventu- gioma, high-grade glioma) and metastatic neoplasms
ally leads to disruption of vessel wall layers and aneu- (e.g., atrial myxoma, chorion carcinoma) have been
rysmal dilatation. reported to cause neoplastic aneurysms. Occasionally
Traumatic aneurysms account for 0.2% to 1% of all squamous cell carcinomas invade the branches of the
intracranial aneurysms (5%–15% in children) and are ECA and cause an oncotic pseudoaneurysm, which
the most common cause of intracranial pseudoaneu- may result in exsanguinating epistaxis.
rysm (its wall is not composed of normal vessel wall
layers but consists of cavitated clot) (Figure 5-33). They Which Types of Aneurysms May Be Related
usually result from indirect trauma from closed head to Vascular Malformations?
injury, such as shearing injury or impaction of an artery High-flow states such as arteriovenous malformations
against a dural fold, such as the distal ACA against the (AVMs) and AVFs can increase hemodynamic stress on
falx cerebri. They may also be caused by direct pene- vessel walls and induce the formation of so-called flow-
trating trauma or a contiguous skull fracture. The most related aneurysms (Figure 5-13, C and D). The reported
frequently encountered traumatic aneurysm location association with AVMs are in the range from 5% to 15%.
is the cavernous ICA segment (48%), which is typi- Such aneurysms are thin-walled structures that eas-
cally associated with basal skull fractures. These aneu- ily rupture with sudden increase of intravascular pres-
rysms might enlarge and produce a cavernous sinus sure. Among patients with ruptured AVMs, 80% harbor
syndrome with nerve compression, or they might sec- flow-related aneurysms. They occur as intralesional
ondarily rupture, producing a carotid–cavernous fis- (intranidal/perinidal) or feeding artery aneurysms. True
tula (CCF). Transdural leakage will lead to SAH. The intranidal aneurysms may be best detected by superse-
most dangerous form is a medial tear of the ICA with lective angiography.
240 Section II  Procedures

A B C

D E F

G H I
 Chapter 5 Diagnostic Angiography 241

Figure 5-33 Different imaging modalities performed in a 17-year-old patient with severe traumatic head injuries following a motor vehicle

SECTION II
accident. A: Noncontrast enhanced computed tomographic (CT) image of the head showing a depressed fracture of the right cranial vault in the
frontotemporal area (white arrow). An acute extradural hemorrhage is demonstrated (black arrowheads). Mass effect with midline shift as well as
bifrontal intracranial air is also shown. B: After initial surgical decompression and evacuation of the patient’s extradural hematoma, a follow-up
CT was performed. The coronally reconstructed image, bone window settings, shows a heavily displaced fracture of the central base of skull with
multiple fragments of the walls of the sphenoid sinus (white arrows) that partially involve the intracranial segments of the right internal carotid
artery (ICA). C, D: Axial sources images of CT angiogram revealing two traumatic aneurysms (white arrows) located in the supraclinoid (C6) por-
tion of the right ICA and in the left P1 segment of the left posterior cerebral artery, just proximal to the posterior communicating artery junction.
The right ICA aneurysm demonstrates marked peripheral thrombus formation (white arrowheads). Selective right ICA angiograms, anteroposterior
(AP) view, in early arterial phase (E) and later arterial/capillary phase (F) show a laterally pointing bilobulated aneurysm located in the superior
C6 ICA segment (white arrow). Intraaneurysmal pooling of contrast is noted during the later angiographic phase (white arrow). G: Selective left
vertebral artery angiogram, Towne AP view, showing large aneurysm in the left P1 segment of the posterior cerebral artery. Volume-rendered
reconstructed images derived from three-dimensional rotational angiograms of right ICA (H) and left vertebral artery (I) show detailed views of
both traumatic aneurysms relative to branching vessels and their parent arteries. The left P1 aneurysm reveals a rough and irregular luminal surface
(white arrow) due to the presence of intrasaccular thrombus.

What Are the Most Important Predisposing in risk of SAH is observed, with an absolute lifetime risk
Conditions for the Development and Progression of 26%. The prevalence of incidental aneurysms among
of Intracranial Aneurysms? symptom-free first-degree relatives from families with
two or more affected members ranges between 8% and
Under Which Circumstances Is Aneurysm 20.6% depending on the history of cofactors such as
Screening for Individuals Advised? smoking and hypertension. Therefore, individuals with
two or more first-degree relatives from such families con-
What Are Important Risk Factors for Rupture stitute a high-risk group, so noninvasive MRA screening
of Aneurysms? is suggested, particularly in the presence of other modi-
The genesis, progression, and rupture of cerebral aneu- fiable risk factors. Screening for intracranial aneurysms
rysms are not well understood. Most intracranial aneu- also has suggested in asymptomatic ADPKD patients.
rysms are acquired lesions from hemodynamic stresses When aneurysm screening is undertaken in such indi-
and degeneration of the vessel wall most pronounced viduals, the potential future risk of aneurysm treatment
at arterial bifurcations. The understanding of hemody- should be taken into consideration. If a first screening
namic flow patterns as important (co-)factors for the is ­negative, repeated screening should be advised after 5
pathogenesis and rupture of cerebral aneurysms has years (risk of finding an aneurysm is 7%).
been enhanced by computational flow modeling and Other conditions associated with an increased preva-
MR derived in vivo flow measurements (Figure 5-34). lence of aneurysms are congenital heart disorders, anoma-
A spectrum of inherited and acquired processes may lous vessels, arterial fenestrations (Figures 5-23 and 5-35),
predispose to aneurysm formation by weakening the vasculopathies (e.g., fibromuscular dysplasia), and sickle cell
vessel wall matrix. Inherited connective tissue dis- disease.
orders are rare (5% of all aneurysms); therefore, the Modifiable risk factors for aneurysm rupture include
number of patients associated with SAH is small but smoking, arterial hypertension, excessive alcohol con-
include those with Ehlers-Danlos syndrome (EDS) type sumption, and possibly the use of estrogens.
IV (large- and medium-sized artery aneurysms, spon- For unruptured aneurysms, data from the Interna-
taneous CCF, arterial dissection), Marfan syndrome tional Study of Unruptured Intracranial Aneurysms
(saccular, fusiform, or dissecting aneurysms), and neu- (ISUIA) showed that the 5-year cumulative rupture
rofibromatosis type 1 (NF1) (stenosis, aneurysm, or fis- rate was relatively low (0.1%) for small aneurysms (<7
tula formation). mm) in the anterior circulation in patients without
The most important unchangeable risk factors are a history of previous SAH. This risk increased to 2.5%
so-called familial intracranial aneurysms (10% of cases to 50% depending on aneurysm size and location
of SAH) and autosomal dominant polycystic kidney disease (posterior circulation including PCoA artery aneurysms
(ADPKD, <1% of cases of SAH). Approximately 25% of have higher rupture risk than anterior circulation aneu-
patients with ADPKD have an intracranial aneurysm at rysms). However, these results derived from a large
autopsy, and the risk of developing de novo aneurysms multicenter prospective trial were often criticized for limi-
is increased in ADPKD patients. Familial intracranial tations mainly related to sample size asymmetries within
aneurysms are a distinct disease entity that affects at groups and a relatively short follow-up period (<5 years
least two or more first-degree relatives in the same family in 50%). Other population-based studies confirmed large
with aneurysmal SAH in the absence of other predispos- ­aneurysm size, posterior circulation location, and history
ing heritable disorders. The age at onset is late, aneu- of previous SAH as independent predictors of aneurysm
rysms tend to be larger and multiple, multiple modes of rupture. Slightly higher rupture rates for small aneurysms
inheritance are observed, and genetic testing is not yet (<5 mm) were possibly related to racial differences,
available for this disease. If only one first-degree relative with Japanese and Finnish ­descendents having a higher
is affected, the estimated lifetime risk of SAH remains ­potential for rupture. Other patient characteristics, such
limited (3.3% vs 0.6% in the general population). as age greater than 60 years, female gender, and aneu-
However, with two or more affected relatives, a steep rise rysm characteristics (e.g., increasing size and symptoms
242 Section II  Procedures

A B C

D E F Figure 5-34 Series of images

demonstrate the stepwise con-
struction of a patient-specific
vascular computational fluid
dynamics (CFD) model generated
for evaluation of intra-aneurysmal
flow dynamics. A, Original 3D
rotational angiography image. B,
Smoothed image. C, Segmented
image. D, Initial vascular recon-
struction. E, Vessel geometry after
deformable model and interactive
truncation of arterial branches.
F, Finite element grid. G, Peak
G H I pressure distribution. H, Mean
wall shear stress distribution. I,
Definition of cut plane used to
visualize velocity pattern. J–L,
Intra-aneurysmal flow velocity on
cut plane at different instants dur-
ing the cardiac cycle. (From Cebral
JR, Castro MA, Burgess JE, Per-
golizzi RS, Sheridan MJ, Putman
CM. Characterization of cerebral
aneurysms for assessing risk of
rupture by using patient-specific
computational hemodynamics
J K L models. AJNR Am J Neuroradiol
2005;26:2550-2559)

other than SAH caused by the aneurysm) were found to aneurysm enlargement of 10% (mean observation
be associated with a higher risk of rupture in a meta-anal- period approximately 4 years) in other studies.
ysis. Morphologic indicators of rupture risk include the
presence of lobulations (Figure 5-36) or daughter aneu- Where Are Intracranial Aneurysms Commonly
rysms (“blebs”) and a high aspect ratio (defined as the Located, and What Is Their Clinical Presentation?
ratio of depth to neck size of a cerebral aneurysm) (Figure Intracranial aneurysms usually arise on the circle of
5-37). Willis or at the MCA bifurcation (Figure 5-38). Approx-
Studies have addressed the question of aneurysm imately 90% are located in the anterior circulation and
enlargement of nonruptured aneurysms under serial only 10% in the vertebrobasilar circulation. Specific
MRA or CTA imaging surveillance. The yield of short- common sites include the ACoA complex (30%–35%),
term follow-up by CTA or MRA (1-year interval) of small internal carotid–posterior communicating artery
(<5 mm) unruptured aneurysms in high-risk patients (30%–35%), MCA bifurcation or trifurcation (20%),
(history of previous SAH or familial intracranial aneu- and tip of the BA (5%). Aneurysms typically are lesions
rysms) is very low (growth rate 3.2%). Large aneurysm in adults (peak presentation at age 40–60 years). The
size (>8 mm) was the only independent predictor for most common clinical manifestation of symptom-
further aneurysm enlargement, with a frequency of atic intracranial aneurysm is SAH. In 85% to 95% of
 Chapter 5 Diagnostic Angiography 243

SECTION II
A B
Figure 5-35 A: Left internal carotid artery angiogram, anteroposterior view, showing a bilobulated aneurysm at the internal carotid artery (ICA)
termination (large black arrow). A short, fenestrated M1 segment is present (black arrowhead) as a normal variant. The perforating M1 branches
(lateral lenticulostriate arteries) originate from the smaller superior limb of the fenestration. A tiny second aneurysm is evident at the early middle
cerebral artery bifurcation (small black arrow). B: Computed tomographic angiography, corresponding anteroposterior thick maximal intensity
projected image, showing the ICA termination aneurysm (large white arrow) and the fenestrated M1 segment (small white arrow). The small second
aneurysm is not visualized. (Courtesy Dr. William McAuliffe, Perth.)

patients with SAH, headache is the most common fissure suggest MCA location; interhemispheric SAH
symptom. Much rarer clinical manifestations include may occur with ACoA aneurysms; and hemorrhage in
cranial neuropathy as the second most common pre- the fourth ventricle and cerebellopontine angle cisterns
sentation (isolated oculomotor nerve [III] palsy is is often associated with a ruptured PICA aneurysm. A
the most frequent finding), seizure, TIA, and cerebral pattern of perimesocephalic SAH can be associated with
infarction. Unruptured aneurysms occasionally are vertebrobasilar aneurysms but also with nonaneurysmal
misdiagnosed clinically as optic neuritis or migraine hemorrhage.
headache, sometimes delaying diagnosis of potentially
fatal lesions for years. What Are the Most Important Factors that
Intracranial aneurysms are rare in children (<2% of Determine Clinical Outcome after Aneurysmal
all cases) and have different characteristics in the pediat- Rupture?
ric group compared to adults: male predominance (3:1); The short-term outcome of an aneurysm rupture is gen-
aneurysms are more common in posterior circulation or erally dismal, with an overall 30-day survival of 40%
distal to circle of Willis (nearly 20%) and at ­terminal to 57%. The long-term outcome of aneurysm rupture
ICA bifurcation (25%–50%); giant aneurysms (>2.5 is variable, with permanent neurologic disability occur-
cm) are common in children; mass effect is a common ring in a significant number of survivors. Besides higher
presenting symptom (approximately 20% of cases); and grades on the Hunt and Hess and Fisher CT scales,
aneurysms are more frequently associated with trauma aneurysm size greater than 10 mm, patient age greater
(up to 20%) and infection. than 50 years, giant aneurysm, and posterior circulation
aneurysm are other factors that are associated with a
What Is the Patient’s Clinical Status in poor outcome. Data from the International Subarach-
Acute SAH, and How Does It Determine the noid Aneurysm Trial (ISAT) showed that in patients with
“Hunt and Hess” Clinical Classification? a ruptured aneurysms, for which endovascular coiling
The most widely used method for clinical grading of and neurosurgical clipping are therapeutic options, the
SAH is the Hunt and Hess Scale (Table 5-2). Imaging outcome in terms of survival free of disability at 1 year is
of acute SAH usually is performed using nonenhanced significantly better with endovascular coiling.
CT scans, although MR sequences such as FLAIR imag- If a patient survives the initial hemorrhage from an
ing also can be used for diagnosis. The severity of SAH aneurysm rupture, a number of delayed complications
on nonenhanced CT is assessed using the Fisher Scale can develop that still may be devastating, such as focal
(Table 5-3). However, this score does not necessarily hematoma with mass effect, including cerebral hernia-
correlate with patient clinical symptoms or aneurysm tion syndromes, hydrocephalus, and cerebral ischemia
size. The location of SAH can sometimes suggest the site with stroke. The latter may be caused by thromboem-
of a ruptured aneurysm: focal hematomas in the sylvian bolic events from the aneurysm sac or most commonly
244 Section II  Procedures

A B

C D
Figure 5-36 Noncontrast computed tomographic (CT) images (A, B) in a patient who presented with subacute retroorbital headache and confu-
sion showing an intracranial hematoma located in the middle cranial fossa adjacent to the left cavernous sinus (large white arrows). A history of trauma
was denied. In addition, a small left hemispheric subdural hematoma (small white arrows) and subdural blood along the left-sided tentorium (white
arrowheads) is depicted. Subarachnoid blood is not found on CT imaging. Lateral (C) and lateral oblique (D) projections of selective left internal
carotid artery (ICA) angiogram show a multilobulated left posterior communicating artery aneurysm (large white arrow). The origin (white arrowhead)
of the posterior communicating artery (small black arrow) is located in the vicinity of the aneurysm neck. The left anterior choroidal artery (small white
arrow) arises from the ICA C7 segment clearly separated from the aneurysm neck. Acute subdural hematoma is a rare but well-recognized presentation
of ruptured posterior communicating aneurysms, and the presumed mechanism is the formation of arachnoid adhesions from the aneurysmal wall
that allow direct bleeding into the subdural space in the absence of subarachnoid hemorrhage. (Courtesy Dr. William McAuliffe, Perth.)
 Chapter 5 Diagnostic Angiography 245

Table 5-2 Hunt and Hess Clinical Grading Scale for

SECTION II
Intracranial Aneurysms
Grade Clinical Condition
Depth 0 Unruptured
I Asymptomatic or minimal headache, nuchal rigidity
II Moderate to severe headache, nuchal rigidity, no neu-
Neck width rologic deficit other than cranial nerve palsy
III Drowsiness, confusion, mild focal deficit
IV Stupor, moderate to severe hemiparesis, possible early
decerebrate rigidity and vegetative disturbances
Depth
Aspect Ratio =
Neck width V Deep coma, decerebrate rigidity, moribund appearance
Figure 5-37 Anatomic relationship between neck width and depth +1 For vasospasm or systemic disease
(neck to dome distance) of a typical berry-type cerebral aneurysm.
The aspect ratio (ratio between depth and neck width) was defined As described in Hunt WE, Hess RM: Surgical risks as related to time of interven-
as an anatomic measure and indicator of rupture risk by Ujiie et al. tion in the repair of intracranial aneurysms. J Neurosurg 28:14-20, 1968.
(Redrawn from Ujiie H, Tamano Y, Sasaki K, Hori T. Is the aspect ratio
a reliable index for predicting the rupture of a saccular aneurysm? Table 5-3 Density of SAH as Revealed by CT Imaging:
Neurosurgery 2001;48:495-502; discussion 502-493.)
Fisher Scale
Score Description
0 Unruptured
1 No blood detected
Anterior 2 Diffuse or vertical layers <1 mm thick
Anterior cerebral
communicating artery 3 Localized clot and/or vertical layer ≥1 mm
artery
Middle 4 Intracerebral or intraventricular clot with diffuse or no
Internal cerebral subarachnoid hemorrhage
carotid artery
Adapted from Fisher CM, Kistler JP, Davis JM: Relation of cerbral vasospasm
artery
to subarachnoid hemorrhage visualized by computerized tomographic
­scanning. Neurosurgery 1980;6(1):1-9.
Posterior Posterior
communicating cerebral
artery c­ omponents of the circle of Willis, the MCA, and both
artery
PICAs must be visualized. At a minimum, standard AP,
Basilar lateral, and both 30-degree transorbital oblique views
artery should be included, but additional views (e.g., submen-
Posterior inferior
cerebellar artery Vertebral tovertex projection) are often needed. If the ACoA does
artery not fill spontaneously, injection of one ICA during tem-
porary cross compression of the contralateral carotid
may be required to visualize this important poten-
tial site of aneurysm. In cases of a hypoplastic PCoA,
Figure 5-38 Common sites of intracranial aneurysms on the circle temporary ipsilateral carotid compression during the
of Willis at the base of the brain. (Redrawn from Schievink WI. Intra-
cranial aneurysms. N Engl J Med 1997;336:28-40.) vertebrobasilar study may show transient reflux of the
PCoA. If reflux from the dominant VA into the contra-
lateral VA is not sufficient to completely visualize both
PICAs, a separate injection of the nondominant vessel
as a result of cerebral hypoperfusion due to vasospasm. may be required (Figure 5-2). Assessment of cross-flow
Untreated ruptured aneurysms carry a high risk of patterns between different circulations is most helpful if
rebleeding (at least 50% of untreated aneurysms rehem- temporary or permanent occlusion of the parent vessel
orrhage within 6 months). becomes necessary during therapy.
For decision making (endovascular vs surgical
Angiographic Evaluation therapy) and planning of therapy (e.g., simple coil
of Intracranial Aneurysms embolization of aneurysm vs balloon-assisted coiling
procedure), delineation of the aneurysm neck is most
What Are the Optimal Angiographic Views important. Second, defining the presence of branches
and Modalities (2D vs 3D Rotational DSA) for that may arise from the aneurysm or near the neck of the
Visualization of Intracranial Aneurysms? aneurysm is essential (Figure 5-39). Instead of obtain-
A technically adequate and complete cerebral angio- ing multiple projections, most centers currently perform
gram in patients with a possible intracranial aneurysm a 3D rotational angiogram directly after the angio-
includes evaluation of the complete intracranial circula- graphic standard projections (Figures 5-26, D). This
tion with multiple projections of each vessel studied. All study can facilitate the determination of the optimal
246 Section II  Procedures

A B C

D E
Figure 5-39 Serial lateral views (A–D) and anteroposterior (AP) view (E) of the right internal carotid artery angiogram in a patient harboring a
giant fusiform distal middle cerebral artery (MCA) aneurysm. A slow pattern of inflow into the large aneurysm sac (large white arrows) and outflow
from the aneurysm sac into two small M3 branches (small black arrows) of the MCA are noted at the early (A) and late (B) arterial phases. The slug-
gish flow within these two arterial branches (small black arrows) persists during the capillary (C) and early venous phases (D). Such hemodynamic
information may be essential for therapy planning in order to determine the safety of anticipated parent artery occlusion, which was successfully
performed in this patient (images not shown). E: Selective right internal carotid artery angiogram, AP view, demonstrating a tapered narrow
aneurysmal neck (black arrowhead) arising from a large sylvian (M2) branch of the MCA. The origins of the two M3 arteries (small black arrows) are
located on the aneurysmal dome (large white arrows). (Courtesy Dr. Tejinder Pal Singh, Perth.)

working projection and thereby decrease the total num- particular importance if parent vessel occlusion is con-
ber of DSA exposures. Moreover, a clear benefit com- templated (Figures 5-30, A and B, and 5-39).
pared to 2D DSA projections is better visualization and Other angiographic findings that should be actively
understanding of complex anatomic ­vascular patterns looked for in patients with ruptured aneurysms include
(e.g., relationship of aneurysm to parent/branching vasoconstriction (common with hyperacute SAH or
vessel in ACoA complex or MCA bifurcation/trifurca- delayed in cerebral vasospasm), ischemia and infarction
tion) as well as better visualization of the aneurysm (unusual in the setting of acute SAH but occur as delayed
neck. With 2D DSA imaging, small aneurysms may be complications in cerebral vasospasm), and mass effect
obscured by overprojection of adjacent vessels. Studies (from focal hematoma or partially/completely throm-
have demonstrated that 3D rotational angiography can bosed aneurysm). Avascular mass effect is demonstrated
depict considerably more small additional aneurysms by stretching and draping of adjacent vessels.
than 2D DSA. It also can detect small treatable ruptured It is important to screen the complete basal cere-
aneurysms in a high proportion of cases with DSA-neg- bral circulation for the presence of multiple aneurysms
ative aneurysmal SAH. For these reasons, 3D rotational (Figure 5-30). When more than one aneurysm is pres-
DSA has been proposed as the new gold standard for ent, identifying which aneurysm likely ruptured is
detection of aneurysms. Disadvantages of 3D rotational essential for treatment planning. The only true but very
DSA compared to 2D DSA are the higher contrast load rare sign of contrast extravasation indicates active bleed-
per acquisition run (18–24 ml vs 6–8 ml), its tendency ing from an aneurysm. Other helpful but not reliable
to overestimate aneurysmal neck width, and the lon- signs include size (the larger aneurysm is more likely
ger acquisition time (6–8 seconds), which makes the to have ruptured), irregularity (presence of “blebs,”
examination more prone to degraded image quality by ”daughter aneurysms,” and/or a multilobulated dome)
motion artifacts in uncooperative patients. Under such (Figures 5-17 and 5-35), and focal mass effect from a
circumstances, it preferentially should be performed hematoma. Most helpful, however, is a correlation of
under general anesthesia directly preceding endovascu- aneurysm sites with the pattern of SAH distribution on
lar therapy of the targeted aneurysm. Another benefit of head CT.
2D DSA projections is its capability to evaluate intra­ In giant aneurysms (>25 mm, 5% of all aneurysms),
aneurysmal and parent vessel flow patterns that are of exact delineation of the aneurysm neck relative to its
 Chapter 5 Diagnostic Angiography 247

parent vessel may be difficult due to the presence of Problem Solving: What Are the Benefits

SECTION II
multiple layers of organized thrombus or obscuring lob- and Shortcomings of CTA for Imaging Cerebral
ulations on standard 2D DSA. A 3D rotational angio- Aneurysms?
gram or a rapid-sequence 2D DSA acquisition may be
helpful in such instances. Problem Solving: Can CTA Study Replace the
Small saccular aneurysms that are completely throm- Invasive Catheter Angiogram in Case of Acute
bosed may be invisible on DSA. True aneurysm must be SAH?
distinguished from aneurysm mimics such as vascular Based on the recent advances in CT technology that have
loops (differentiated by multiple projections or 3D rota- resulted in the outstanding accuracy of the latest 16- and
tional DSA) and infundibuli (most commonly located 64-row multidetector CTA technique, many institutions
at the PCoA origin, less commonly at the AChA origin) have changed their diagnostic imaging algorithm for
as described earlier (see section on Internal Carotid patients presenting with SAH and now routinely apply
Arteries) (Figure 5-6, A). CTA for this indication. Furthermore, management
decisions (e.g., endovascular vs surgical treatment of an
Angiogram-Negative SAH acutely ruptured aneurysm) may be solely based on CTA
findings, with direct progression to craniotomy in some
What Is the Best Way to Follow Up on cases. However, the sensitivity of CTA for the diagno-
Patients with Acute SAH and Initially sis of a cerebral aneurysm is still imperfect compared
Negative Angiogram? to catheter angiography, mainly owing to its inferior
It is important to ensure that any angiographic exami- maximum spatial resolution (0.35–0.5 mm vs 0.1. mm
nation of patients with nontraumatic SAH is complete in conventional DSA and 0.2–0.3 mm in 3D rotational
because an incomplete angiogram is the most ­common angiography). Along with the implementation of new
cause of negative findings. In 10% to 20% of patients with diagnostic algorithms, a discussion has emerged in the
verified SAH, the initial technically adequate catheter scientific literature as to the optimal diagnostic test for
angiogram is negative. Possible causes include so-called patients presenting with acute SAH. Our current prac-
nonaneurysmal perimesencephalic hemorrhage, throm- tice is to apply CTA as the first-line investigation that is
bosed aneurysm, vascular lesions of the spine, spinal performed immediately after plain CT study in patients
neoplasms, pregnancy-induced hypertension, sympa- with proved SAH. This is followed by a conventional
thomimetic drug abuse, bleeding disorders, and antico- catheter angiogram, including a 3D rotational angi-
agulants/antiplatelets. Investigators have ­demonstrated ography study. Characterization of aneurysms and the
that repeat angiography performed approximately 1 further management plan are derived from the two
week after the ictus is the most sensitive imaging modal- imaging modalities in a side-by-side analysis as we con-
ity for detecting a lesion causing the hemorrhage, the sider them complementary examinations for the follow-
most common being an aneurysm that has been throm- ing reasons.
bosed during the initial angiogram. The yield of a second First, a valuable benefit of an initial noninvasive
angiogram is best for patients with a classic SAH pattern workup includes obtaining knowledge of the vascular
(8%–46%), followed by a perimesencephalic hemor- anatomy before invasive catheterization or endovascu-
rhage pattern (0%–7%), and is worst in patients with lar therapy, which can help in tailoring a DSA exami-
a negative CT scan and positive lumbar puncture (0%). nation or avoid the risks of difficult catheterizations in
Contrast-enhanced MRI of the brain and spine may only the individual patient (e.g., in the case of severe ath-
be occasionally helpful in detecting hemorrhagic tumors eromatous disease at the neck arteries). For example,
such as cervical ependymoma, spinal cavernous angi- if a ruptured aneurysm has been confirmed on DSA in
oma, or AVM in patients with an atypical presentation the anterior circulation and the CTA study is of opti-
for aneurysmal SAH. The value of performing a third mal quality allowing for accurate evaluation of the
angiogram several weeks after the ictus is debatable due vertebrobasilar arteries, a full “four-vessel” DSA may
to a low overall yield, but it may have a role in the man- not be conducted. Therefore, potentially risky cath-
agement of selected patients (e.g., those with a dense eter maneuvers can be avoided if access to the VAs is
classic SAH pattern or suspicious wall irregularity on sec- complex. Second, apart from luminographic details,
ond angiogram). The role of noninvasive CTA or MRA as CTA can provide more precise information on intraa-
a follow-up test has not been established in the setting neurysmal thrombus and calcified components of the
of an initially negative angiogram. However, its use has aneurysm/vessel walls compared to DSA. Third, CTA
been suggested for subpopulations of patients for whom can demonstrate reliable bony landmarks that can dif-
the risk-to-benefit ratio favors a noninvasive test, such as ferentiate between intradural or extradural aneurysms
those with perimesencephalic hemorrhage. involving the (para-)clinoid ICA segment, such as the
optic strut, which may facilitate treatment decisions
Noninvasive Evaluation of (Figure 5-40).
Intracranial Aneurysms However, DSA is still required because its higher
spatial resolution enables better characterization of the
Noninvasive methods of assessing the intracranial cir- neck and identification of smaller but often crucial ves-
culation for the presence of an unruptured intracranial sels relative to the aneurysm/parent artery complex, such
aneurysm or for follow-up of treated intracranial aneu- as the AChA or recurrent artery of Heubner. Second,
rysms include MRA and CTA. any negative CTA warrants further DSA investigation
248 Section II  Procedures

A B C

D E F
Figure 5-40 Anteroposterior oblique (A), lateral (B), and Haughton lateral oblique (C) views of the left internal carotid artery angiogram show
a large multilobulated aneurysm (large white arrows) in the paraclinoid region of the internal carotid artery, which points superomedially. It is
impossible to determine the relationship to its apparent broad neck to the clinoid segment of the internal carotid artery (extradural vs intradural
vs transitional location) on the different angiographic views. Moreover, the origin of the ophthalmic artery (small black arrow) cannot be separated
from the aneurysm neck. The presence of a fetal variant of posterior cerebral artery (black arrowhead) is demonstrated. Computed tomographic
angiography (CTA) (D–F) can be useful for determining exactly the location of the aneurysm neck with respect to bony landmarks, which can
serve as reliable indicators for the dural rings. D: Axial source image at level of partially pneumatized optic strut (large black arrows) showing the
inferior portion of the broad-necked aneurysm pointing medially into the sella (large white arrow). E: Subsequent higher axial image at level of
anterior clinoid process (black arrowheads) showing further neck parts of the aneurysm neck (large white arrow) involving the ophthalmic portion of
the internal carotid artery (small white arrows), which is clearly in a subarachnoid location. The optic strut (large black arrows), which is the inferior
bony root of the anterior clinoid process (black arrowheads), separates the superior orbital fissure (small black arrow) from the optic canal (white
arrowhead). The anterior boundary of the clinoid segment of the internal carotid artery and its inferior boundary accurately localizes the point at
which the internal carotid artery pierces the proximal dural ring (oculomotor membrane) and exits the cavernous sinus. This serves as a very use-
ful landmark for determining the partially subarachnoid location of the neck in this aneurysm. F: Sagittally reconstructed CTA image showing the
relationship of the whole wide aneurysm neck. It is defined as transitional because it is mostly located in the clinoid (C5) segment at the level of
the optic strut (large black arrow) but also involves the cavernous segment (C4) with an inferior locule (black arrowhead) and the ophthalmic seg-
ment (C6, small white arrow) with the larger superior locule (large white arrow). The optic canal (white arrowhead) is demonstrated superior to the
optic strut. (Courtesy Dr. Tejinder Pal Singh, Perth.)

because CTA alone may give a false-negative result (neg- the need for sufficient time to review CTA images. In
ative predictive value of CTA ranges between 82% and addition, distinct sources of SAH, such as a blood blis-
96%). These mostly relate to aneurysms smaller than 3 ter-like aneurysm, pial AVMs, or AVFs with pial drain-
to 4 mm or aneurysms in arteries adjacent to bone or age, and intracranial dissection may not be visible on
venous structures (cavernous, clinoid, and ophthalmic CTA. There also is a remote possibility that an aneurysm
ICA segments). Interestingly, many small aneurysms detected on CTA may not be the source of hemorrhage if
that are first missed on CTA become evident after review a patient harbors other smaller aneurysms that can only
of the DSA examination. This fact points to the impor- be resolved on DSA.
tance of the reading radiologist’s awareness of potential Hence, we suggest to solely skip the DSA examination
CTA pitfalls and interpretation errors (e.g., infundibu- in patients with ruptured aneurysms who present with
lum vs small aneurysm), the use of a good workstation/ extensive intraparenchymal hemorrhage and mass effect
software for 3D and multiplanar reconstructions, and requiring immediate craniotomy for ­decompression
 Chapter 5 Diagnostic Angiography 249

and hematoma evacuation. In addition, there is signifi- Problem Solving: What Is the Role of CTA in the

SECTION II
cant potential for CTA in cases where aneurysms are of Follow-up of Clipped Aneurysms?
low likelihood, such as subarachnoid blood in patients Although not useful for the evaluation of coiled
after significant trauma or in patients without hemor- aneurysms, CTA is far superior to MRA for the evalu-
rhage but with severe headaches and a family history of ation of aneurysms after surgical clipping because
aneurysm. of the substantial artifacts on MR images created by
the available surgical clips, which usually completely
Angiographic Follow-up of Treated obscure the immediate perianeurysmal region. Using
Aneurysms the latest technology CT scanners (16- to 64-section
multidetector row CT scanners) and optimized imag-
Problem Solving: What Is the Role of MRA ing parameters (optimal scanning pitch to minimize
in the Follow-up of Coiled Aneurysms? clip-related artifacts is approximately 0.6 mm), CTA
With the increasing use of endovascular therapy as pri- often can effectively depict and follow small aneu-
mary treatment of ruptured and unruptured intracra- rysm remnants; demonstrate patency, stenosis, or
nial aneurysms, continued angiographic surveillance vasospasm in the adjacent parent vessels; and provide
of aneurysms after coil embolization has become stan- surveillance of the entire cerebrovasculature for de
dard practice. This is mainly because recurrence after novo aneurysms after surgical clipping. In the intra-
coil embolization due to compaction of the original operative or immediate postoperative period, CTA
coil mass or migration of the coil mass into intraa- imaging may be required to evaluate aneurysm resid-
neurysmal thrombus has been estimated to occur ual and parent vessel compromise. Although the risk
in 10% to 40% of patients. Some investigators have for recurrence of a clipped aneurysm is low, evidence
recommended that at least two follow-up examina- indicates that aneurysm recurrence as well as de novo
tions should be performed within the first year after aneurysm formation with subsequent SAH can occur
treatment. However, minimizing morbidity related to even after successful surgical treatment. This evi-
angiographic follow-up is particularly important in dence supports the use of routine periodic imaging
the context of the very low risk of rerupture after suc- surveillance after successful surgical clipping. How-
cessful coil embolization, which is estimated between ever, extensive artifacts due to multiple clips, older-
0.11% and 0.21%. MRA is very attractive for this pur- generation cobalt-containing clips, or unfavorable
pose because platinum alloys used in aneurysm coils clip position relative to the area of interest, as well as
create relatively little distortion of local magnetic field. arterial segments encased within osseous structures
The resultant images are minimally affected by coil- (e.g., near the skull base) and poor examination qual-
induced artifacts in comparison to CT/CTA images, ity (e.g., suboptimal timing of contrast bolus) may
which usually are severely degraded by streak and beam obscure the aneurysm and adjacent parent vessel
hardening artifacts that typically obscure not only the and preclude the noninvasive evaluation with CTA.
aneurysm but also the adjacent parent/branching ves- In these cases, conventional catheter angiography,
sels and the surrounding brain parenchyma. Despite which remains the standard of ­reference for follow-
the application of different MRA techniques (e.g., 3D up of clipped aneurysms, should be used to resolve
TOF and contrast-enhanced MRA), the reported sen- any cases of diagnostic uncertainty.
sitivity and specificity rates for detection of residual
aneurysms range between 90% and 100%. The initial Cerebral Vascular Malformations
MRA study should be performed in close temporal
proximity to the initial endovascular treatment (24–48 Problem Solving: How to Classify Cerebral
hours) in order to provide a direct correlation with the Vascular Malformations?
immediate posttreatment DSA (Figure 5-27) and the Is AV Shunting Present? If Not, Could
baseline examination for subsequent comparison with the Cerebral Vascular Malformation Be a
serial MRA studies. In addition, the baseline MRA indi- Developmental Venous Anomaly, Cavernoma,
cates whether MRA can be used effectively as a follow- or Capillary Telangiectasia?
up technique in the future, because the initial baseline Cerebral vascular malformations have been classified
MRA–DSA correlation in some patients may be unreli- according to a combination of anatomic and histopath-
able (e.g., artifact related to the presence of aneurysm ologic features, clinical presentation, biologic behavior,
clips, aneurysms with particularly complex anat- and imaging characteristics. The presence or absence of
omy, or complex stent and coil constructs). In these AV shunting within a cerebral vascular malformation
patients, follow-up is performed primarily by conven- is the fundamental distinguishing feature (Table 5-4).
tional angiography, which remains the gold standard Noninvasive vascular imaging studies such as CTA or
for evaluation of treated aneurysms. Moreover, DSA MRI/MRA usually are the initial investigations and are
should be liberally used to resolve any cases of diag- sufficient to diagnose cerebral vascular malformations
nostic uncertainty on the noninvasive imaging test or without AV shunting, such as cavernoma, capillary tel-
to verify the diagnosis of small aneurysm recurrences angiectasis, or developmental venous anomaly (DVA).
identified by MRA and to ensure an accurate estima- However, diagnostic catheter angiography remains the
tion of the size. In patients not requiring retreatment, gold standard for delineating the detailed angioarchi-
these small recurrences may be subsequently followed tecture of a vascular malformation and planning the
noninvasively. appropriate therapy.
250 Section II  Procedures

Table 5-4 Classification of Cerebral Vascular Table 5-5 Spetzler-Martin Arteriovenous Malformation
­Malformations Grading System

Cerebral vascular malformations with arteriovenous shunting Feature Points Assigned

Arteriovenous malformation
Plexiform nidus Size of arteriovenous malformation (cm)
Mixed (plexiform–fistulous) nidus Small (<3) 1
Arteriovenous fistula
Single or multiple fistulae Medium (3–6) 2
Monopedicular or multipedicular
Large (>6) 3
Cerebral arteriovenous malformations without arteriovenous Eloquence of adjacent brain
shunting
Capillary telangiectasis Noneloquent 0
Developmental venous anomaly
Venous varix without associated arteriovenous malformation Eloquent 1
or arteriovenous fistula Venous drainage
Cavernous malformation (cavernoma)
Superficial only 0
Modified from Osborn AG: Diagnostic Cerebral Angiography. Lippincott Williams
& Wilkins; 1999. Deep 1

Grade is total of assigned points for size and eloquence plus venous drainage
Arteriovenous Malformations (grade 6 is reserved for inoperable lesions).
Modified from (Hamilton MG, Spetzler RF: The prospective application of a
Problem Solving: What Are the Characteristics grading system for arteriovenous malformations. Neurosurgery 34(1):2-6;
discussion 6-7, 1994.
of AVMs, and Which Factors Determine Their Risk
of Hemorrhage? that the risk of hemorrhage of an AVM can be widely
Problem Solving: What Features Determine the variable (from 0.9% to 34.4% per year), depending
Spetzler-Martin Grading: Is the AVM 3 Cm or on various clinical and morphologic characteristics. In
More? Is the Nidus Located in Eloquent Brain? a single-center cohort study that evaluated the natural
Is Deep or Superficial Venous Drainage Present? history of AVM, the highest hemorrhage rates per year
AVMs are most common type of cerebrovascular malfor- were found for AVMs with initial hemorrhagic presen-
mations that exhibits AV shunting. They are composed tation (7.5%), associated aneurysms (5.4%), and pres-
of a collection of dysplastic plexiform vessels that are ence of deep venous drainage (6.9%). These factors were
supplied by one or more arterial feeders and drained by demonstrated to be independent risk factors for future
one or more venous channels. AVMs may have a pure hemorrhage from AVMs. Furthermore, lesions that pres-
plexiform nidus or contain a mixed plexiform–fistulous ent with hemorrhage or have associated aneurysms have
nidus. On gross pathology, they appear as tightly packed a risk of rebleeding twice that of AVMs without these
masses of abnormal vascular channels and may contain characteristics, and the risk is highest in the first years
small amounts of gliotic brain, dystrophic calcification, after diagnosis. AVMs with associated aneurysms have a
and blood products. Other abnormalities associated higher risk of hemorrhage even 5 years after diagnosis.
with AVMs include flow-related aneurysms and endo- A study disclosed a lower morbidity from spontaneous
thelial remodeling with resulting angiopathy in both AVM hemorrhage either at initial presentation or dur-
the feeding arteries and the draining veins. Chronic ing follow-up of untreated patients compared to intra-
regional arterial hypoperfusion and venous hyperten- cranial hemorrhage from other causes. Data from the
sion may cause cerebrovascular steal with resulting atro- most recent studies suggest that the natural history risk
phy in otherwise normal brain at a distance from AVMs. for patients with unruptured AVMs is far more benign
The majority of AVMs are located in the cerebral hemi- than for those who present with rupture, and concerns
spheres, and 15% occur in the posterior fossa. Depend- were raised about the actual benefit of invasive treat-
ing on their location, they can be classified as superficial ment strategies, particularly for this cohort of patients.
(convexity) or deep (ratio 2:1 to 3:1). A combination A large international, randomized controlled multi-
of high-resolution MRI and selective angiography is center trial (A Randomized Trial of Unruptured Brain
required for complete anatomic localization and delin- AVMs [ARUBA]) is currently underway to determine
eation of AVMs. Only 2% of AVMs are multiple; these the natural history versus treatment-related risks of best
occur almost exclusively in the setting of neurocutane- interventional therapy in nonruptured AVMs.
ous syndromes such as hereditary hemorrhagic telangi- A widely used grading system to guide patient man-
ectasis or Wyburn-Mason syndrome. The incidence of agement and determine the treatment-related risk and
sporadic solitary AVMs in the general population is esti- prognosis of an AVM is the Spetzler-Martin grading system
mated between 0.04% and 0.52% (autopsy series data). (Table 5-5), which was introduced in 1986 to ­predict
Approximately 50% of patients with AVMs pres- surgical morbidity and mortality. The total grade (1–5)
ent with symptoms caused by hemorrhage. Other than reflects the sum of points assigned for AVM size, elo-
seizure (25%), nonhemorrhagic focal neurologic syn- quence of the adjacent brain, and pattern of venous
dromes such as ischemia are relatively infrequent. The drainage.
majority of AVMs become symptomatic by age 50 years The angiographic evaluation of a cerebral AVM
(peak age at initial presentation 20–40 years), but 25% includes a selective and often superselective investiga-
of AVMs hemorrhage by age 15 years. Reports indicate tion of the AVM itself as well as the remainder of the
 Chapter 5 Diagnostic Angiography 251

SECTION II
A B

C D
Figure 5-41 Right internal carotid artery angiograms, anteroposterior (A) and lateral (B) views, with early arterial phase study showing tem-
poral arteriovenous malformation (AVM) supplied by several enlarged middle cerebral artery (M2) branches with a relatively compact nidus
structure. C, D: Subsequent lateral arterial phase images illustrating venous drainage pattern with enormous varices of deep draining basal vein of
Rosenthal (large white arrow) leading to early opacification of the straight sinus (white arrowhead) and transverse sigmoid sinuses. Superficial drain-
age occurs via several temporal cortical veins (small black arrows). Findings are consistent with a grade III AVM (Spetzler-Martin scale). (Courtesy
Dr. William McAuliffe, Perth.)

cerebral vasculature. A selective, technically complete neoplasm. Identification of both flow-related arterial
angiogram of an AVM should provide detailed informa- and venous angiopathy (enlargements, stenoses, occlu-
tion on the individual feeding arteries and their vascu- sions, venous varices) and the presence of an aneurysm
lar territories, the size, shape, and flow conditions of the (flow-related feeding artery aneurysm or perinidal/
AVM nidus, as well as delineate the venous drainage pat- intranidal aneurysms) should also be made (Figure
tern (individual veins, deep vs superficial drainage, col- 5-42). Venous drainage of the normal brain should be
laterals, reflux into normal veins/sinus) (Figure 5-41). assessed (venous hypertension?). AVMs should be stud-
AV shunting is present when contrast filling of drain- ied using high-resolution DSA with high frame rates.
ing veins appears abnormally early in the angiographic Depending on the planned treatment, consistent mag-
sequence. Although this is characteristic of an AVM, it nification factors and calibrated markers may also be
may occur with other pathologies such as ischemia and suggested.
252 Section II  Procedures

A B

C D
Figure 5-42 A: Lateral projection of the left internal carotid artery angiogram showing an arteriovenous malformation (AVM) located on the
tentorium in the temporooccipital lobe. It is composed of a relatively compact nidus (large white arrow) with major arterial feeders from the left
posterior temporal artery (white arrowheads) and the posterior temporal branch from the middle cerebral artery (small black arrow). B: Lateral view
of the selective left vertebral artery angiogram at early arterial phase showing filling of an intranidal aneurysm (large white arrow). In addition to
the main posterior temporal artery feeder (white arrowhead), the left calcarine artery (small black arrow) shows AVM supply. C: Subsequent later
arterial phase showing venous drainage from the AVM nidus (large white arrow) into enlarged cortical veins (white arrowheads) with subsequent
early filling of the superior sagittal sinus (large black arrow). Some of these veins demonstrate varicose dilatations (small black arrow). D: Selective
left external carotid angiogram, lateral view, demonstrating recruitment of transdural arterial supply to the AVM (large white arrow) from the pos-
terior division of the left middle meningeal artery (small black arrow). (Courtesy Dr. Tejinder Pal Singh, Perth.)

A superselective angiography of an AVM using micro- and proximal segments of draining veins (stenosis, out-
catheters is often combined with endovascular treat- let obstruction, varices).
ment. This method can provide extensive, detailed Occasionally unusual variants of AVMs may be found.
information regarding the internal angioarchitecture of A diffuse AVM is an infiltrating lesion that involves an
an AVM. This includes anatomy, hemodynamics (e.g., entire lobe or hemisphere of the brain. Angiographically,
flow-related vasculopathy) of the distal segments of such lesions appear as a diffuse collection of multiple
feeding arteries, arterionidal junction, compartments of arterial feeders and draining veins without a compact
the nidus, plexiform portions, AVFs, intranidal cavities nidus. They may be very large but cause almost no dis-
(aneurysm, posthemorrhagic arterial and venous pseu- cernible mass effect. Clinically these lesions often pres-
doaneurysms, venous ectasia), veno–nidal junction, ent with intractable seizures rather than symptoms of
 Chapter 5 Diagnostic Angiography 253

hemorrhage. Diffuse AVMs may exhibit a “proliferative appear and its caudal remnant remains as the vein of

SECTION II
angiopathy” pattern that continues to recruit additional Galen. Angiographically, a typical VGAM consists of
feeding vessels. Pial AVMs of sufficient size may recruit one or more enlarged arteries that drain directly into a
transdural arterial supply from a dural vessel such as the massively enlarged vein of Galen. On the basis of their
middle meningeal artery or meningohypophyseal trunk angioarchitecture, a mural form and a choroidal form can
(Figure 5-42). Rarely AVMs are part of a mixed vascu- be identified in true VGAMs depending on the relation-
lar malformation such as AVM–DVA (sometimes called ship of the arterial feeders to the prosencephalic vein.
arterialized venous malformation) or AVM–capillary telan- Mural VGAMs demonstrate a direct fistula in the wall
giectasias. of the prosencephalic vein. The arterial feeder complex
AVMs may hemorrhage and then thrombose spon- usually is less extensive and the rate of flow less severe
taneously, or thrombosis may be induced by ste- than in the choroidal type (complex feeder network from
reotactic radiosurgery. Angiograms in patients with bilateral sources). Their arterial supply usually involves
completely thrombosed AVMs may appear normal, all the choroidal arteries: the medial and lateral pos-
show an avascular mass effect, or demonstrate only terior choroidal arteries and the AChAs. In addition,
subtle AV ­shunting (early draining vein without iden- branches from the pericallosal arteries and thalamoper-
tifiable feeding vessels or nidus). Occasionally, irregu- forating branches can contribute to the supply of these
lar-appearing arteries are present with slow flow that lesions. Venous drainage from the aneurysmal dilatation
persist into late arterial/capillary phases; these are of the vein of Galen (a venous varix) is complicated by
termed stagnating arteries. This subset of AVMs should thrombosis or absence of the straight sinus with drain-
be referred to as angiographically occult AVM (some- age into the falcine sinus in the majority of cases. Distal
times erroneously termed cryptic AVM). Similar find- outlet venous stenosis can occur, and dilated choroidal
ings can be present on postoperative angiograms of veins may be present, draining anteroinferiorly into the
surgically excised AVMs. cavernous sinus. Clinically, neonatal VGAMs usually
present with high-output congestive heart failure, tachy-
Arteriovenous Fistulae cardia, respiratory distress, and cyanosis.
Cerebral (pial) AVFs are rare in contrast to dural
Problem Solving: How to Classify Intracranial arteriovenous fistulae (DAVFs). Their angiographic
AVFs? appearance consists of one or more dilated, often
AVFs are much less common than AVMs and are charac- bizarre-looking pial arteries that drain directly into a
terized by direct shunts between pial arteries and venous venous channel. Stenosis of the draining vein, which
channels. Two major forms exist: the vein of Galen aneu- can result in sudden thrombosis and hemorrhage, is
rysmal malformation, which occurs predominantly in commonly seen.
neonates and infants, and the pial or subependymal AVF.
Malformations involving the vein of Galen have been Cerebral Vascular Malformations
classified into four groups: (1) true vein of Galen aneurys-
without AV Shunting
mal malformation (VGAM); (2) vein of Galen dilatation
that occurs secondary to high-flow subpial AVM drain- Problem Solving: Is DSA Needed to Diagnose
ing into this vessel; (3) vein of Galen varix that is a vari- a Cavernoma or a DVA?
cose dilatation of the vein of Galen in children without Cerebral vascular malformations without evidence of
an underlying AV shunt and either represents a transient AV shunting arise from postarteriolar vessels and can
and asymptomatic dilatation of the vein of Galen in be categorized into capillary, venous, and cavernous
neonates presenting with cardiac failure or is associated malformations. Because these lesions either represent
with complex DVAs draining an entire hemisphere into usually angiographically occult vascular malformations
the deep venous system; and (4) dural vein of Galen (capillary telangiectasias and cavernous angioma) or can
dilatation, which is an acquired lesion that develops be sufficiently diagnosed and characterized with non-
in the wall of the vein of Galen or at the venous–sinus invasive imaging modalities such as CTA or MRI/MRA
junction and nearly always is secondary to straight sinus imaging (DVA, capillary telangiectasias, and cavernous
thrombosis in adults or very rarely in children second- angioma), they are not discussed in detail in this chapter.
ary to a complete thrombosis of the vein of Galen or of Isolated DVAs are generally thought to be congeni-
the falcine sinus. tal and to follow a clinically asymptomatic course.
Typically they are diagnosed incidentally during imag-
Problem Solving: What Is the Importance of the ing investigations for unrelated symptoms. In contrast
Choroidal Arteries and Median Prosencephalic to the benign course of isolated DVAs, up to one third
Vein in a True VGAM? of all DVAs are associated with cavernoma, which may
True VGAMs represent an AVF in the wall of a persistent present with neurologic symptoms attributable to the
embryonic venous channel called the median prosence- cavernoma itself and/or its hemorrhagic complications.
phalic vein, which lies in the roof of the diencephalon Very rare variants are termed atypical or mixed DVAs.
and drains into a primitive accessory sinus, the falcine These represent arterialized DVAs or are associated with
sinus, which courses posterosuperiorly within the falx an AVM nidus that uses the DVA portion of the lesion as
to connect to the superior sagittal sinus. Usually the a drainage route. Clinically, patients with these lesions
median prosencephalic vein regresses by week 10 of fetal often present with intraparenchymal hemorrhage.
development as the definitive internal cerebral veins The appearance of atypical DVA on noninvasive imag-
254 Section II  Procedures

ing modalities such as CTA and MR/MRA may be very Table 5-6 Cognard Classification Scheme of Venous
similar to that of nonarterialized DVA. Its angiographic Drainage in Dural Arteriovenous Fistulas
appearance consists of an identifiable arterial compo-
Type I Anterograde drainage into a sinus
nent that is either an AVM nidus or multiple tiny dilated
arterial feeders, with each vessel acting as a single micro- Type IIa Reflux into the sinus (retrograde flow)
AVF that drains directly into the medullary veins, which Type IIb Reflux into cortical veins
are organized into a classic caput medusae. The etiopa-
thology of DVAs associated with arteriovenous shunting Type IIa + IIb Reflux into both sinus and cortical veins
or AVM is still unknown and remains speculative, but it Type III Direct cortical venous drainage without
is assumed that these lesions are at greater risk for devel- venous ectasia
oping complications than simple DVAs and that their Type IV Direct cortical venous drainage with venous
natural history resembles that of classic AVMs. ectasias
Type V Spinal venous drainage
Dural AVF
Modified from Cognard C, Gobin YP, Pierot L, Bailly AL, Houdart E, Casasco
Problem Solving: What Is the Definition of a A, Chiras J, Merland JJ: Cerebral dural arteriovenous fistulas: clinical and
angiographic correlation with a revised classification of venous drainage.
Dural Arteriovenous Shunt and How Best to Radiology 194(3):671-680, 1995.
Classify These Shunts?
AVFs that involve the dura and the epidural space are stressed the role of activation or stimulation of angio-
termed dural arteriovenous shunts (DAVSs) or dural arte- genesis within the dura in the development of DAVF.
riovenous fistulae (DAVFs). These lesions are much more DAVFs may occur at any age and are not uncommon
common than cerebral AVFs. They comprise 10% to in children, but most become symptomatic between 40
15% of intracranial arteriovenous malformations and and 60 years of age. Their clinical presentation is highly
can be either congenital or acquired. In general, three varied and is primarily determined by the location of
types are recognized: dural sinus malformation with the fistula and the subsequent venous drainage pattern.
arteriovenous shunt, infantile DAVS, and adult DAVF; For DAVFs involving the transverse or sigmoid sinuses,
the latter is the most common type. headache and bruit are the most common presenting
Dural sinus malformations are uncommon lesions symptoms. Proptosis, chemosis, retroorbital pain, and
found in neonates or infants. They usually consist ophthalmoplegia are commonly associated with cavern-
of giant venous pouches or dural lakes involving the ous sinus lesions. Other manifestations include pulse-
superior sagittal sinus with thrombosis, occlusion, or synchronous tinnitus, cranial neuropathy, and even
hypogenesis of one jugular bulb. They show slow-flow potentially reversible vascular dementia due to venous
communications with other venous sinuses or veins. hypertensive encephalopathy. Although most DAVFs
DAVSs are demonstrated within the wall of the venous have a benign natural history even with reported spon-
lake. Infantile DAVSs are rare and often multifocal. They taneous involutions, lesions with aggressive behavior
typically are seen as large sinuses with multiple arte- resulting in neurologic deterioration and oftentimes
riovenous shunts and large arterial feeders. Secondary intracranial hemorrhage can occur and be fatal.
induced cortico–pial shunts are common. In contrast
to adult-type DAVFs, most infantile DAVS have high Problem Solving: What Determines the Prognosis
flow rates and volumes. Spontaneous thrombosis of the in DAVFs and How to Classify Their Venous
venous outflow may lead to increased intracranial pres- Drainage Patterns?
sure hydrocephalus, cerebral venous ischemia, and the The pattern of venous drainage is the single most impor-
so-called melting brain syndrome. tant determinant of clinical presentation, neurologic sta-
Adult-type DAVFs consist of numerous abnormal tus, and long-term prognosis of DAVFs. Therefore, the
direct communications, so-called crack-like vessels, most useful and modern classification schemes that were
between dural arteries and veins without an interven- proposed by Cognard et al. and Borden et al. focus on the
ing capillary bed. In contrast to AVMs, DAVFs have different venous drainage patterns (Table 5-6). Reflux into
no true nidus. They are located in the dural wall of a cortical veins or direct cortical venous drainage with or
venous sinus, not within the sinus itself. The most com- without venous ectasias worsens the prognosis of DAVF.
mon sites are the transverse and sigmoid sinuses; the Stenosis or thrombosis of venous drainage is also asso-
cavernous sinus is also a frequent location. With the ciated with an indicator of a bad prognosis. For DAVFs
exception of bilateral cavernous sinus lesions, most near the cavernous sinus, the Barrow classification system
DAVFs are solitary lesions. Their precise etiology is still based on the arterial supply is widely used (see section on
debated, but many of these lesions seem to be acquired Traumatic Arterial Injuries: Traumatic AV Fistulae).
secondary to venous hemodynamic compromise, such Angiographically, most DAVFs have multiple dural
as stenosis, thrombosis, or occlusion of a dural venous arterial feeders (Figure 5-43). The most commonly
sinus. Recanalization of the compromised vessel lumen involved vessels that supply a DAVF are transmastoid
leads to an enlargement, and microscopic arteriovenous branches of the occipital artery and meningeal branches
shunts, which normally are present in the sinus wall, of the ECA (e.g., neuromeningeal branch of ascend-
may enlarge and form numerous small microfistulae, ing pharyngeal artery, branches of middle meningeal
resulting in a DAVF. Due to the common association artery). Tentorial and dural branches of the ICAs and
with a previous sinus thrombosis, investigators have VAs are other frequently contributing feeders (Figure
 Chapter 5 Diagnostic Angiography 255

SECTION II
A B C

D E F
Figure 5-43 A, B: Left common carotid artery angiogram, lateral view, in arterial phase showing abnormal early venous contrast filling of left
transverse sigmoid sinus consistent with dural arteriovenous fistula (DAVF) (A). Major arterial supply originates from transmastoid branches of
enlarged left occipital artery (large black arrows). B: Superselective left occipital artery angiogram, lateral view, illustrating typical arterial network
consisting of numerous small transmastoid and dural crack-like vessels that supply multiple tiny micro-AVFs within wall of dural sinus (white
arrowheads). Venous reflux into contralateral transverse sinus is depicted (large white arrow). This is a type IIa DAVF (Cognard scale). C: Super-
selective left ascending pharyngeal artery angiogram, lateral view, showing additional arterial feeders from both anteriorly located pharyngeal
trunk (large black arrow) and posterior neuromeningeal trunk (small black arrow) of ascending pharyngeal artery (large white arrow). Posteriorly
the neuromeningeal trunk supplies large network of shunts to jugular bulb through its jugular branch. Anteriorly, fine lateral clival and superior
pharyngeal artery (via foramen lacerum) branches anastomose with dural internal carotid artery (ICA) branches (tentorial branches of meningo-
hypophyseal artery and inferolateral trunk) to give additional fistula supply (white arrowheads). These anastomoses are potentially dangerous col-
lateral vessels toward the ICA system when performing transarterial embolization procedures. D: Left ICA angiogram, lateral view, demonstrating
enlarged tentorial branches of the meningohypophyseal trunk (white arrowheads) as well as small pial temporal middle cerebral artery branches
that supply the DAVF (small black arrow), resulting in faint opacification of left sigmoid sinus (large black arrow). E: Selective left vertebral artery
angiogram, lateral view, illustrating numerous other small pial feeding vessels from left superior cerebellar artery and anterior inferior cerebel-
lar artery branches. F: Axial three-dimensional time-of-flight magnetic resonance image showing typical hyperintensities within the left sigmoid
sinus/jugular bulb (large white arrow) as well as hyperintensities adjacent to these veins (white arrowhead), which correspond to high-flow signal
derived from arterialized sinuses and feeding arteries. (Courtesy Dr. William McAuliffe, Perth.)

5-13). Numerous arteriovenous microfistulae form a Noninvasive Imaging Modalities

fine vascular network in the wall of the affected dural
sinus. Determining the type of DAVF (e.g., Cognard Problem Solving: What Is the Role of Modern
I–V) depends on accurate assessment of the venous CTA and MRA Imaging Modalities in Vascular
drainage pattern and hemodynamics. Delineation of Malformations with AV Shunting?
the flow (anterograde vs retrograde) within the involved Modern high-resolution multidetector CTA imaging and
sinuses or cortical veins (e.g., vein of Labbé) is impor- fast time-resolved 3D MRA techniques have been shown
tant. Reflux into cortical or spinal perimedullary veins to reliably enable the diagnosis of cerebral AV shunting
(Figure 5-44) and venous ectasias must be noted. Dural lesions such as AVM and DAVF.
sinus stenosis or occlusion is a common but invariably Static CTA techniques appear advantageous in the
seen finding. emergent setting with patients presenting acutely with
256 Section II  Procedures

A B C

D E F

Figure 5-44 A: T2-weighted magnetic resonance image of the cervical spine in sagittal ori-
entation showing extensive central intramedullary edema involving the medulla oblongata as
well as cervical and upper thoracic cord with prominent epimedullary flow voids (small white
arrows). B: Corresponding T1-weighted image (with sat saturation) after gadolinium adminis-
tration showing massive intramedullary contrast enhancement in these areas. C: Early arterial
phase image, lateral view, of superselective angiogram with catheter tip located in right ascend-
ing pharyngeal artery (large black arrow). A dural arteriovenous shunt is located at the right
craniocervical junction and is supplied by small jugular (small black arrow) and hypoglossal
branches of the neuromeningeal trunk of the ascending pharyngeal artery. Venous drainage is
directed into dilated veins of the anterior medullary venous (AMV) system (large white arrows in
C and D). D: Subsequent later arterial phase image showing further inferior drainage into the
grossly enlarged anterior spinal vein (small black arrows) (corresponding to grade V dural arte-
riovenous fistula on Cognard scale). The odontoid arch system, an important arterial arcade
surrounding the dens, is filled via the hypoglossal branch of the neuromeningeal trunk of the
ascending pharyngeal artery (small white arrows in C and D). At the C2–3 intervertebral space
it anastomoses with the vertebral artery, which shows faint opacification (white arrowheads in C
and D). This anastomosis poses an important potential hazard when performing embolization
procedures for this arteriovenous shunt. E: Unsubtracted lateral view of superselective right
ascending pharyngeal angiogram showing location of fistula at craniocervical junction with
G feeding neuromeningeal trunk (white arrow) and anterior spinal venous drainage (small black
arrows) posterior to odontoid peg. F: Superselective angiogram of right occipital artery, lateral
view, demonstrating additional arterial supply of fistula from a small transmastoid branch of
occipital artery (small white arrow) via tiny meningeal vessel (small black arrows) to shunt into
AMV/anterior spinal vein (white arrowheads). G: Targeted maximal intensity projected recon-
structed image of superselective right occipital artery three-dimensional rotational angiogram
(DynaCT) is useful for accurate anatomic localization of the fistula point relative to overlaid
bony landmarks at the skull base. The fistula point is confined by a transition in vessel caliber
from a tiny transmastoid arterial feeder (white arrowhead) to the retroclival convoluted bridging
vein (thin white arrow). This can be identified at the right jugular foramen (large white arrow).
Subsequent caudal venous drainage through the foramen magnum into the midline anterior
spinal vein is also delineated. (Courtesy Dr. Tejinder Pal Singh, Perth.)
 Chapter 5 Diagnostic Angiography 257

SECTION II
Table 5-7 Classification of Intracranial Nonatheromatous Vasculopathies
Inflammatory Vasculopathy—Vasculitis
Primary angiitis of the CNS Systemic vasculitis with CNS Systemic diseases with CNS diseases with
involvement ­secondary CNS angiitis ­secondary vasculitis
Polyarteritis nodosa Systemic lupus erythematosus Meningitis (pyogenic,
Hypersensitivity granulomatosis Antiphospholipid syndrome fungal, parasitic,
(Churg and Strauss) Scleroderma t­uberculous, syphilitic)
Wegener granulomatosis Rheumatoid arthritis Septic emboli
Behçet´s disease Sjögren´s syndrome Sarcoid
Giant cell arteritis
Takayasu arteritis
Temporal arteritis
Noninflammatory Vasculopathy
Inherited disorders Oncotic vasculopathy Radiation-induced ­ Idiopathic progressive
Neurocutaneous syndromes Tumor emboli vasculopathy arteriopathy of childhood
Neurofibromatosis type 1 Pseudoaneurysm Moyamoya disease
Tuberous sclerosis Intravascular lymphoma
Menkes kinky hair disease
Ehlers-Danlos type IV
Sickle cell disease
Reversible Vasculopathy Syndromes
Reversible cerebral vasoconstriction Posterior cerebral encephalopa-
syndrome thy syndrome may coexist with
Pregnancy and puerperium reversible cerebral vasoconstric-
Vasoactive drug and blood product tion syndrome
exposure
Miscellaneous
Headache disorders
(e.g., migraine)
Idiopathic

CNS, Central nervous system.

intracranial hemorrhage or clinical suspicion of a vas- C-arm ­flat-panel detector angiography system, provides
cular malformation. However, precise assessment of additional information in the evaluation DAVFs com-
arterial feeders, fistula points, and grading of venous pared to 2D DSA. This method especially enhances
drainage still is impossible on static CTA images. The detailed visualization of fistulous points and small ves-
newest generation of multirow CT scanners (64 or sels in relation to fine osseous structures, which may be
320 rows) offers the possibility of generating dynamic very useful for planning endovascular or surgical treat-
images of the cerebrovascular circulation covering a ment of DAVFs (Figure 5-44, G).
large area of interest (e.g., entire head), and reported
preliminary results for the diagnosis and classification Vasculitis, Reversible Cerebral
of cranial arteriovenous shunts appear promising. Vasoconstriction Syndromes, and
Dynamic, contrast-enhanced MRA methods that gen-
Noninflammatory Vasculopathies
erate images at high spatial and temporal resolutions
can be used to diagnose and characterize AVMs with Problem Solving: What Is the Role of Catheter
regard to main arterial feeders, nidus size, major drain- Angiography in Suspected Cerebral Vasculitis?
ing veins, and the Spetzler-Martin grading. They can How Specific Are Vasculitis-like Changes on
be used for image-guided radiosurgery of intracranial DSA, and What Conditions Other than Cerebral
AVMs or during follow-up of treated AV shunts to reduce Vasculitis May Show Similar Findings?
radiation exposure to patients. However, they are not Atherosclerosis is by far the most common cause of a
capable of replacing DSA for comprehensive character- vasculitis-like angiographic pattern in adults. However,
ization of AVMs and DAVFs. The relatively lower spatio- a large variety of congenital and acquired nonathero-
temporal resolutions and nonselective mode of vascular ­ matous disorders or conditions can produce cerebral
visualization are limitations for a robust depiction inflammatory vasculopathies, noninflammatory vas-
of small or low-flow AV shunting lesions, intranidal/ culopathies, or reversible vasculopathy syndromes
feeding artery aneurysms, and feeding arteries/pedicles. (Table 5-7).
For these reasons, the catheter angiogram is still con-
sidered the standard of reference for diagnosis, grading, Neurocutaneous Syndromes and
and therapy planning in AV shunting lesions. Equivo-
Inherited Vasculopathies
cal findings on noninvasive CTA or MRA studies should
directly prompt further investigation with DSA. A number of inherited disorders can involve the intra-
The application of dynamic intraarterial CTA cranial arteries. NF1 and tuberous sclerosis are the two
(Dyna­CT digital angiography), which uses a biplane phakomatoses that most often cause cerebral vascular
258 Section II  Procedures

manifestations. Slowly progressive stenotic or occlu- only test that allows for definite diagnosis, although the
sive lesions of the supraclinoid ICAs may cause an result may be negative in some cases owing to a patchy
angiographic moyamoya pattern to develop in NF1. distribution of histologic involvement. Studies have
Less commonly aneurysms (see section on Indica- shown that typical angiographic features of vasculitis do
tions/Aneurysms), ectasias, or fistulae in the large- and not reliably identify patients with primary angiitis of the
medium sized arteries are encountered in NF1. Ehlers- CNS proved on biopsy by neuropathologic criteria. The
Danlos syndrome (type IV) is characterized by spontane- sensitivity of these findings was reported as low as 10%
ous vessel ruptures, dissections, aneurysm formation of to 20% when small-vessel involvement was present, and
large-and medium sized arteries, or spontaneous direct the ability to distinguish vasculitis from other disorders
CCFs. Sickle-cell disease causes vascular occlusions or ranged between 24% and 60%.
endothelial damage from sickled red cells, and neuro- Several types of systemic necrotizing vasculitides
logic complications including stroke are commonly may involve the cerebral vasculature with nonspecific
encountered (25% of cases). Angiographically, stenosis angiographic findings. The most common types are
of the supraclinoid ICAs and the proximal ACA/MCA polyarteritis nodosa and hypersensitivity (allergic) angiitis
segments may result in a moyamoya pattern often seen and granulomatosis (Churg-Strauss). In systemic lupus
in sickle cell disease. Multiple aneurysms in this disorder erythematosus, neurologic involvement with stroke is
also have been reported (see section on Indications/ common, but true cerebral vasculitis is rare; the angio-
Aneurysms). gram is most commonly normal. The causes of stroke in
systemic lupus erythematosus include thrombosis sec-
Moyamoya Disease ondary to hypercoagulopathy from antiphospholipid
syndrome, emboli from Libman-Sacks endocarditis,
Idiopathic progressive arteriopathy of childhood, also accelerated atherosclerosis, and cerebral vasculitis (pri-
called moyamoya disease, is an arteriopathy of unknown mary lupus vasculitis or secondary to CNS infection).
etiology that has two peak ages of presentation in Japan Antiphospholipid syndrome is characterized clinically
and Pacific rim countries: childhood (early onset) and by strokes at an unusually early age, recurrent arterial
adulthood (late onset). Children usually present with and venous thromboses, infertility and spontaneous
ischemic symptoms, whereas adults also commonly fetal loss, and thrombocytopenia. The most commonly
present with intracranial hemorrhage. The prognosis encountered angiographic abnormalities are solitary
in this disorder depends on the rapidity and extent of stem or distal branch occlusions; however, vasculitic
vessel occlusions as well as the development of effective patterns and nonatherosclerotic great vessel origin ste-
collaterals. The classic angiographic pattern consists of nosis also may occur.
stenosis or occlusion of the distal ICAs with ­collateral Other systemic diseases that may cause CNS vascu-
circulation from multiple enlarged lenticulostriate and litis include scleroderma, rheumatoid disease, and Sjögren
thalamoperforating arteries that resemble a “puff of syndrome. Behçet disease, which is classically character-
smoke,” which is the translation of the Japanese word ized by recurrent oral and genital ulcers and uveitis,
“moyamoya.” Widespread dural, leptomeningeal, and may also cause CNS vasculitis involving small- and
pial collaterals also may develop. This so-called angio- medium-sized vessels. Parenchymal lesions in the basal
graphic moyamoya pattern is nonspecific and has been ganglia, brainstem, and cerebellum are typical on MRI,
reported in a number of disorders other than idiopathic but cerebral venous thrombosis and meningitis also
progressive arteriopathy of childhood, such as NF1, may occur.
radiation therapy, sickle cell disease, and atheroscle- Infective pyogenic, granulomatous, fungal, and para-
rosis. Moyamoya disease is also associated with other sitic meningitis as well as sarcoidosis have a predilection
vascular anomalies (e.g., aneurysms, AVMs, ectasias, fen- for the basal cisterns and commonly narrow the ter-
estrations). minal ICA and the proximal MCA and ACA segments.
Other infectious causes of intracranial vasculopathy
Inflammatory Vasculopathy— include human immunodeficiency virus, cysticercosis,
Vasculitis Lyme disease, and meningovascular syphilis.
Neoplasms with tumor emboli may cause pseudo­
Inflammatory vasculopathies (true vasculitides) can be aneurysms and intracranial vascular stenosis. Lympho-
subdivided into primary (isolated) angiitis of the CNS proliferative diseases such as angiocentric large cell
and systemic vasculitic diseases with secondary CNS lymphoma may present initially with vasculitis.
involvement (Table 5-7). The angiographic imaging
appearance of the intracranial vasculitides is nonspecific Noninvasive Imaging Alternatives
and similar, regardless of specific etiology. Multiple seg- Contrast-enhanced, flow-compensated high-resolution
mental smooth or slightly irregularly shaped stenosis T1-weighted MRI has been reported to demonstrate
alternating with dilated segments is typical (Figure 5-45). thickening and contrast enhancement of vessel walls in
Primary angiitis of the CNS is characterized patho- patients with different types of inflammatory CNS vas-
logically by inflammation of the media and adventitia culitis affecting the large arteries of the brain. Although
of preferentially small arterioles and venules (<300 μm the value and diagnostic accuracy of this sign is still
in diameter, which is below the resolution of conven- unclear and warrants additional studies, MRI including
tional DSA); however, vessels of any size can be affected. MRA may be advantageous. Besides visualization of ves-
Invasive brain or leptomeningeal biopsy usually is the sel wall changes, it is capable of showing ­parenchymal
 Chapter 5 Diagnostic Angiography 259

SECTION II
A B

C D
Figure 5-45 Axial T2-weighed (A) and gradient-recalled echo (B) magnetic resonance (MR) images obtained from a patient with new onset of
headaches and left-sided hemiparesis. Imaging findings are consistent with multiple areas of cortical ischemia involving the right temporoparietal
lobe, left thalamus, and left occipital lobe. Contrast-enhanced MR images (not shown) revealed partially enhancing and nonenhancing infarcts
consistent with different age of these lesions. B: Petechial hemorrhages involving infarcted and noninfarcted areas are visualized. A subsequently
performed catheter angiogram revealed typical findings of vasculitis. C: Left internal carotid artery angiogram, lateral view, during arterial phase
showing multiple areas of alternating constrictions and dilatations in the anterior cerebral artery branches (thin white arrows). D: Right internal
carotid artery angiogram, lateral view, during arterial phase showing similarly affected vessels in the middle cerebral artery territory (thin white
arrows). Right frontal brain/leptomeningeal biopsy disclosed mixed inflammatory vessel wall infiltrates with small amounts of fibrinoid necrosis
involving small and large vessels and secondary ischemic brain damage. No evidence of systemic vasculitis was present (negative on screenings for
hypercoagulable disorders and autoantibodies). These findings were consistent with primary CNS vasculitis.

abnormalities (mainly stroke and/or hemorrhages) that probability for vasculitis is high (e.g., in case of multiple
are very common in different types of inflammatory infarcts in different vascular territories on MRI, positive
vasculopathies. However, caliber changes of medium- clinical findings such as headaches, and positive cere-
and small-sized arteries can be reliably depicted only brospinal fluid analysis) due to the low sensitivity and
by catheter angiography compared to current MRA specificity of this method. The combination of normal
­techniques. MRI and cerebrospinal fluid is regarded a very powerful
Despite this potential advantage, the invasive catheter negative predictor in excluding the possibility of CNS
angiogram is considered useful only when the pretest vasculitis in many patients.
260 Section II  Procedures

Table 5-8 Conditions Associated with Reversible Vasculopathy Syndromes

Reversible Cerebral Vasoconstriction Syndromes
Pregnancy and puerpe- Vasoactive drugs and blood products Miscellaneous Headache disorders­
rium, early pregnancy, Phenylpropanolamine, pseudoephed- Hypercalcemia, porphyria, Migraine, primary
late pregnancy, eclampsia, rine, ergotamine, tartrate, Methergine, pheochromocytoma, ­thunderclap headache,
preeclampsia, delayed bromocriptine, lisuride, selective sero- bronchial carcinoid tumor, benign exertional
postpartum eclampsia tonin reuptake inhibitors, sumatriptan, unruptured cerebral headache, benign sexual
isometheptine, cocaine, ectasy, amphet- aneurysm, head trauma, headache, primary cough
amine derivatives, marijuana, lysergic spinal subdural hematoma, headache
acid diethylamide, tacrolimus (FK-506), postcarotid endarterectomy,
cyclophosphamide, erythropoietin, intra- neurosurgical procedures
venous immune globulin, red blood cell
transfusions
Posterior Reversible Encephalopathy Syndrome May Coexist with Reversible Cerebral Vasoconstriction Syndrome
Toxemia of pregnancy Posttransplantation Immune suppression Infection/sepsis/shock
(preeclampsia/eclampsia) Allogeneic bone marrow transplantation, Cyclosporine, tacrolimus Systemic inflammatory
Autoimmune diseases solid organ transplantation (FK-506) response syndrome,
Systemic lupus erythe- Status post chemotherapy Miscellaneous multiorgan dysfunction
matosus, scleroderma, Combination high-dose chemotherapy, Hypomagnesemia, hypercal- syndrome
Wegener, ­polyarteritis cytarabine, cisplatin, gemcitabine, cemia, hypocholesterolemia,
nodosa tiazofurin, bevacizumab (Avastin), kinase intravenous immune globu-
inhibitor BAY 34-9006 lin, Guillain-Barré syndrome

Modified from Calabrese LH, Dodick DW, Schwedt TJ, Singhal AB: Narrative review: reversible cerebral vasoconstriction syndromes. Ann Intern Med 146(1):34-44, 2007;
and Bartynski WS: Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features. AJNR Am J Neuroradiol 29(6):1036-1042, 2008.

Reversible Cerebral Vasculopathy

v­ alidated diagnostic criteria. Currently a large number
Syndromes
of associated conditions have been described, includ-
Reversible cerebral vasoconstriction syndromes (RCVSs) ing uncomplicated pregnancy or puerperium, eclamp-
has been introduced as a descriptive term that sum- sia/preeclampsia, exposure to certain medications or
marizes a group of diverse disorders characterized by drugs (e.g., cocaine, ecstasy, methamphetamines, and a
prolonged but reversible angiographic vasoconstriction spectrum of sympathomimetic drugs), and the setting
of the cerebral arteries. In the past, RCVSs have been of catecholamine-secreting tumors. RCVS also can occur
given various eponymic or syndromic labels, includ- without an identifiable course or in association with
ing Call syndrome (or Call-Fleming syndrome), benign other headache disorders (Table 5-8). Uncertainty exists
angiopathy of the CNS, postpartum angiopathy, thun- in the distinction of RCVS from migraine attacks and
derclap headache with reversible vasospasm, migrain- posterior reversible leukoencephalopathy syndrome
ous vasospasm or migraine angiitis, and drug-induced (PRES) due to overlapping clinical and imaging features.
cerebral arteritis or angiopathy. Clinically these disor- The latter syndrome is characterized by reversible gray
ders typically present with acute-onset severe, “thun- matter and white matter lesions on MRI that often occur
derclap headaches” that recur for a few days, with or in the setting of hypertensive encephalopathy. However,
without additional neurologic signs and symptoms. these lesions have also been described in patients with
Although most patients experience complete resolution presentations or associated conditions typical of RCVS
of ­headache and neurologic symptoms within days to (Table 5-8). Angiographically, PRES findings are con-
weeks, others may be left with permanent neurologic sistent with what is typically described as vasospasm
deficits secondary to ischemic or hemorrhagic stroke. or arteritis, but again reversibility of vasculopathy can
The characteristic angiographic findings in RCVS are be observed on repeat angiographic studies. Therefore,
nonspecific (vasculitis-like), with alternating areas of the suggestion has been made that RCVS and PRES may
arterial constriction and normal vascular caliber or dila- coexist or that RCVS may even be the cause of PRES due
tation, often called beading, in multiple vascular beds to a common pathophysiologic basis consisting of dis-
involving the large and medium cerebral arteries (ante- turbances in cerebral arterial tone with subsequent cere-
rior and posterior circulation). Although rare exceptions bral hypoperfusion in the two syndromes.
exist, the reversibility of vasoconstriction over days to
weeks is the feature that best distinguishes this disorder Cerebral Vasospasm
from true cerebral vasculitis, particularly primary angi-
itis of the CNS, which is the most important differential Cerebral vasospasm following SAH may appear angio-
diagnosis. The distinction of these conditions is impor- graphically identical to RCVS but can be differentiated
tant because the treatment differs for both. Although clinically based on the history and the absence of sub-
catheter angiography is considered the gold standard arachnoid blood. Rarely hyperacute or acute vasoconstric-
technique, some angiographic features can also be dem- tion occurs after SAH, which may cause extensive global
onstrated on serial CTA or MRA. ischemia. Pathologically altered cerebral arterial tone
Understanding of RCVS has been limited by the is the source of vasoconstriction with alternating areas
lack of a unique underlying pathologic basis and of stenosis that affect the proximal as well as the distal
 Chapter 5 Diagnostic Angiography 261

vasculature, which typically is not multifocal but may

SECTION II
mimic a vasculitis-like pattern after SAH ­(Figure 5-46).
This is often disclosed on angiography in patients who
develop secondary neurologic deterioration or ischemic
symptoms with a peak between 4 and 11 days after rup-
ture of an intracranial aneurysm. This condition is a major
cause of morbidity and mortality secondary to SAH.

CAROTID DISEASE, INTRACRANIAL

ARTERIAL STENOSIS, AND TRAUMA
Carotid Stenosis
Problem Solving: What Is the Current Role of DSA
in Atherosclerotic Disease of the Carotid Arteries?
Is the Gold Standard Imaging Technique Still
Required?
Imaging of the carotid artery for screening of critical
stenosis (>70%– 99%) is a very common investigation
that is performed for primary or secondary prevention
of stroke in patients with TIAs or who suffered from
previous stroke. For decision making regarding poten-
Figure 5-46 Right internal carotid angiogram, anteroposterior tial carotid endarterectomy or stenting, quantification
view, obtained 9 days after subarachnoid hemorrhage secondary to a of carotid stenosis according to North American Symp-
ruptured middle cerebral artery aneurysm that had been coil emboli- tomatic Carotid Endarterectomy Trial (NASCET) is the
zed prior to this angiogram. Multiple areas of segmental narrowing in most widely accepted method, although various differ-
the M1 segment and M1/M2 junctions of the middle cerebral artery,
the A1 segment of the anterior cerebral artery, and the suraclinoid ent methods have been used in the past. This trial was
internal carotid artery are seen. These findings are typical of severe based on conventional angiography, so the percent-
cerebral vasospasm. age decrease in residual carotid lumen is estimated by
using ratio calculations from the angiographic projec-
tion showing the “narrowest” stenosis (Figure 5-47).

A B C
Figure 5-47 Left common carotid artery (CCA) angiogram in oblique (A) and lateral (B, C) views showing a high-grade eccentric stenosis of the
proximal internal carotid artery (ICA). A: Eccentric atherosclerotic plaque involving the carotid bifurcation on oblique view of CCA angiogram.
Note subtraction artifact from plaque calcification (black arrowheads). A high-grade stenosis of the proximal ICA (white arrow) is demonstrated.
B: On the lateral view, a carotid stent that was inserted previously into the contralateral ICA is visible (small black arrows). Again, the high-grade
proximal stenosis of the left ICA (white arrow) is shown. C: CCA angiogram, lateral view, is used to measure the diameter of the CCA proximal to
the stenosis and the ICA distal to the stenosis as well as the vessel length to tailor the appropriate size of the carotid stent before treatment of the
ICA stenosis (white arrow). (Courtesy Dr. William McAuliffe, Perth.)
262 Section II  Procedures

Apart from determining stenosis severity (moderate vs A meta-analysis of MRA demonstrated a high diag-
high grade), the angiographic workup needs to provide nostic accuracy of TOF and contrast-enhanced MRA
other important information, including the following. techniques for the detection of high-grade ICA steno-
(1) Identify and accurately discriminate a true ­occlusion sis and occlusions, with contrast-enhanced MRA hav-
from a near occlusion, also called a pseudoocclusion. The ing the edge over TOF MRA. However, the sensitivity of
latter is defined as a very-high-grade stenosis (99%) with both methods for identifying moderate-degree stenosis
distal luminal collapse that may cause very slow antero- was markedly reduced (50%–69%). The distinction of
grade flow with delayed contrast washout. This so-called near occlusion (pseudoocclusion) from true occlusion
string sign occurs when only a trickle of anterograde flow of the carotid artery may be critical for determining
can be detected on late phases of carotid angiograms or patients eligible for carotid endarterectomy or stenting.
color flow Doppler ultrasound. (2) Identify tandem ste- This has often been a diagnostic dilemma for nonin-
notic lesions (e.g., in the carotid siphon or intracranial vasive imaging modalities, and a combination of two
circulation) and evaluate existing and potential path- different modalities, such as carotid ultrasonography
ways for collateral circulation. (3) Identify coexisting as a screening test and MRA and/or DSA for confirma-
atherosclerotic disease (aortic arch, great vessels, intra- tion, has been applied to solve this problem. In this
cranial vessels). (4) Identify intraluminal thrombus, particular subgroup, DSA may be required under rare
which usually occurs at the site of greatest luminal com- circumstances to diagnose a true “string sign,” which
promise and increases the risk of periprocedural throm- represents diffuse luminal narrowing or distal ICA ste-
boembolism during carotid stenting. (5) Identify vessel nosis/occlusion (e.g., in the siphon) with collapsed
tortuosity, configuration, and variants of the aortic arch proximal lumen and cannot be differentiated from near
that may interfere with access for endovascular stenting. occlusions when ultrasound and MRA fail to demon-
(6) Identify plaque ulceration and plaque content/mor- strate a focal high-grade lesion. Alternatively, multide-
phology, which may be used in the future for risk strati- tector CTA, which has proven excellent correlation with
fication in asymptomatic patients or in patients with DSA for the diagnosis of carotid near occlusion, may
moderate stenosis (concept of “plaque vulnerability”). be applied. The accuracy of MRA for detecting lower-
For characterizing plaque morphology (e.g., intraplaque degree stenosis is likely to increase in the future with
hemorrhage), noninvasive techniques such as high-res- the use of modern high-field (3 T) MR scanners with
olution MRA or carotid ultrasound have shown prom- dedicated multichannel neurovascular array coils. In
ising results in published studies and may be applied a report using contrast-enhanced MRA with highly
clinically in the future. Catheter angiography is still con- accelerated parallel imaging techniques at 3 T on an
sidered the gold standard for imaging of carotid stenosis extended field of view (circle of Willis included), the
but has been widely eliminated as a screening method for whole supraaortic arterial tree was imaged at very high
carotid disease. This is mainly due to its invasiveness and spatial resolution (voxel size 0.44 mm3), resulting in
associated risks of stroke, which are particularly high for diagnostic values comparable to DSA for arterial steno-
this subgroup of patients (see section on ­Complications sis detection.
and Risk Factors). Instead, a wide range of noninvasive Whether small differences in the performance of
imaging modalities with their own distinct advantages modern CTA and MRA techniques for carotid stenosis
and drawbacks is currently in use. The techniques most are important for patient outcome and in which cases
often used are carotid duplex and color Doppler flow DSA or a combination of noninvasive methods would
ultrasonography, TOF and contrast-enhanced MRA, and produce the best result are unclear. However, the poten-
CTA. tial risks of DSA should be considered when determin-
The major benefit of CTA is the acquisition of isotro- ing the diagnostic method of choice. After all, the present
pic 3D image data at relatively high spatial resolution situation is notably different from the time of the major
that allows for accurate measurement of luminal dimen- studies on carotid endarterectomy, with advances in the
sions of both carotid arteries in a multiplanar fashion. best medical treatment as well as carotid stenting being
It also may provide additional information on plaque evaluated as an alternative therapy in ongoing random-
content in the arterial wall with or without mural calci- ized multicenter trials (International Carotid Stenting
fications, and extravascular tissues. Another advantage is Study [ICSS] and Carotid Revascularization Endarterec-
a high sensitivity for the detection of distal or tandem tomy vs. Stenting Trial [CREST]).
lesions. For first-generation single-slice CTA, the sensi-
tivity and specificity for detection of 70% to 99% ste- Intracranial Atherosclerosis
nosis and of occlusion were 85% and 93%, and 97%
and 99%, respectively. Using multidetector CTA tech- Problem Solving: Under Which Conditions Is DSA
nology, very high sensitivity and specificity for detection Necessary in Intracranial Arterial Stenoocclusive
of carotid stenosis (>50%) was demonstrated. However, Disease?
compared with 2D DSA, a mild underestimation of ste- Atherosclerotic disease in large intracranial arteries is an
nosis measurements seems to be more common than important and often underrecognized cause of stroke. It
overestimation, but misclassification is reported rare in is estimated to account for approximately 5% to 10% of
careful assessment of images. In fact, the overestimation ischemic strokes in the United States and 33% to 67%
on CTA may be partly related to limited and suboptimal in Asia. Moreover, the overall risk of recurrent ischemic
DSA views that can lead to an underestimation of steno- events may be as high as 15% to 38% per year among
sis degree on DSA. persons with intracranial atherosclerotic disease.
 Chapter 5 Diagnostic Angiography 263

The diagnostic accuracy of CTA for evaluation of considered a method of choice for follow-up imaging

SECTION II
intracranial atherosclerotic arterial stenosis has been after intracranial stent placement.
reported to be very high (97.1% sensitivity, 99.5% speci-
ficity for >50% stenosis) compared to DSA. Furthermore, Ischemic Stroke
CTA detected large arterial occlusion with 100% sensi-
tivity and specificity. Another study demonstrated that Problem Solving: What Are the Indications for
CTA has a higher sensitivity than MRA for intracranial Cerebral Angiography and Typical Angiographic
stenosis and occlusion. TOF MRA, which is routinely Findings of Ischemic Stroke?
performed for visualization of the intracranial arteries, Imaging of acute ischemic stroke including visualization
is limited by a lower spatial resolution than DSA and of intracranial arterial vasculature is not the domain of
CTA and by flow-related artifacts. Particularly in stenotic invasive diagnostic catheter angiography. Besides early
lesions, proton spin dephasing, and consequently flow signs of stroke on CT imaging of the brain, CTA and CT
signal intensity loss, commonly occurs secondary to perfusion imaging can reliably demonstrate major extra-
complex, slow, or in-phase flow. Therefore, TOF MRA cranial and intracranial arterial occlusions, high-grade
is considered more inaccurate in grading stenosis and stenosis or intravascular thrombus, and potentially sal-
tends to overestimate high-grade stenoses. vageable tissue indicated by a penumbra. These exami-
The major limitation of CTA is its inferior spatial nations are widely available, and they are easy and fast to
resolution compared to DSA; however, this is likely to perform on a helical CT scanner. MRI, particularly diffu-
improve in the future with advancing multidetector CT sion-weighted imaging, more accurately detects cerebral
technology. Using current CTA technology for the detec- ischemia within minutes of its onset. MR can also be
tion of stenosis in smaller vessels (diameter <2 mm, used to detect hemorrhage as well as determine the sta-
which is typical for ACA and distal MCA branches), tus of the extracranial and intracranial arteries on MRA.
a slight difference in measurement could potentially A mismatch between findings on diffusion and perfu-
result in a significant difference in the degree of stenosis. sion MR images may be used to predict the presence of
Because CTA is essentially a vessel cast technique, it also a penumbra. These techniques are mainly applied in
provides no significant flow hemodynamic information the setting of acute ischemic stroke to rule out hemor-
as does DSA, which may be very important in determin- rhage and to determine the stroke pattern as well as the
ing related risks and guiding decisions for treatment of risks, benefits, and prognosis of potential candidates for
such lesions. thrombolysis. The so-called therapeutic time windows that
DSA is considered the gold standard in the evalu- allow safe administration of intravenous or intraarterial
ation of intracranial stenosis and occlusion. It pro- thrombolysis therapy are very narrow in these patients.
vides images with high spatial resolution. However, Classically, revascularization treatments for acute isch-
mainly owing to its procedural risks, costs, and limited emic stroke are generally restricted to within 3 hours
­availability, noninvasive CTA and MRA are more desir- of symptom start for ­intravenous tissue plasminogen
able for screening for stenosis in the larger intracranial activator or 6 to 8 hours for intraarterial thrombolysis
arteries and for following patients with such conditions. and mechanical thrombectomy. The report of the Euro-
Of interest, false-positive findings of arterial occlusion pean Cooperative Acute Stroke Study III (ECASS III) trial
in the vertebrobasilar system can rarely occur with DSA demonstrated safety and benefit of intravenous throm-
compared to CTA and are related to low- or balanced- bolysis between 3 and 4.5 hours after onset of symp-
flow states in the setting of severe stenosis. toms. As a consequence, the therapeutic window for
With increasing use of intracranial stents for treating invasive intraarterial therapies may be further narrowed.
intracranial stenosis, symptomatic or asymptomatic in- Alternate triaging methods for endovascular therapies
stent restenosis is a common delayed complication that in patients with acute ischemic stroke have been tested
is reported in up to 30% of cases. The clinically more con- only in small patient collectives and currently still lack
cerning complication of delayed stent thrombosis may validation from large prospective studies.
occur under much rarer instances. To diagnose and dif- Outside the setting of intraarterial thrombolysis
ferentiate these conditions, a vigorous angiographic fol- or endovascular mechanical revascularization proce-
low-up is suggested. Noninvasive angiographic imaging dures, invasive cerebral angiography is not indicated
techniques appear not advantageous for this indication for patients with acute stroke. However, it is important
due to stent-related artifacts. Current case series suggest for an interventional neuroradiologist to be familiar
that current CTA techniques may be prone to misinter- with the angiographic signs of acute cerebral infarction.
pretation of in-stent stenosis and in-stent thrombus, These may occur in the event of a thromboembolic com-
which may result in inappropriate management. Mainly plication when endovascular procedures are performed
owing to its comparable less artifact-affected visualiza- within a brain-supplying artery (e.g., coiling of a cere-
tion of stent struts and stent lumen, angiographic CT bral aneurysm). Early detection of such signs is of partic-
with intravenous contrast application may be a nonin- ular importance in order to prompt salvage maneuvers
vasive alternative technique in the future. This new tech- such as intraarterial thrombolysis, which may poten-
nique provides cross-­sectional CT-like images based on tially reverse major ischemic damage. The most com-
3D rotational radiography performed with a rotating monly encountered sign is the presence of intravascular
C-arm–mounted flat-panel detector. However, to date thrombus, which is seen as a filling defect within the
only case reports have shown promising results with lumen of an opacified vessel, or vessel occlusion. Occlu-
this new technique. In the meantime, DSA should be sion can present as a tapered vessel ­narrowing or abrupt
264 Section II  Procedures

Table 5-9 Craniocervical Collateral Flow

Intracranial
­Anastomoses Extracranial/Intracranial Anastomoses Extracranial Anastomoses
Circle of Willis ECA to ICA Subclavian steal (VA to contralateral
Pial (leptomeningeal) Maxillary artery branches distal subclavian artery)
collaterals MMA or recurrent meningeal artery to ophthalmic artery Carotid steal (CCA occlusion with pat-
Transdural collaterals MMA to ILT ent ECA and ICA, flow reversal in ECA)
Artery of foramen rotundum to ILT VA to VA via segmental branches
Accessory meningeal artery to ILT ECA to ECA via contralateral branches
Anterior and middle deep temporal arteries to ophthalmic artery
Vidian artery to petrous ICA (anterior tympanic artery)
Facial artery (angular branch) to ophthalmic artery
Superficial temporal artery to anterior falx artery
Ascending pharyngeal artery branches
Superficial pharyngeal artery to cavernous ICA (foramen lacerum)
Superficial pharyngeal artery to ILT
Clival rami to cavernous ICA
Inferior tympanic artery to petrous ICA (caroticotympanic artery)
Jugular branch of neuromeningeal trunk to ICA
Stylomastoid artery (from occipital or posterior auricular artery) to petrous
ICA
ECA to VA
Occipital artery branches
Transosseous branches
C1 anastomotic branch (suboccipital ”knot”)
C2 anastomotic branch
Ascending pharyngeal artery branches
Hypoglossal branch (odontoid arch system)
Musculospinal branch
Subclavian artery to VA
Ascending cervical artery branches
C3 anastomotic branch
C4 anastomotic branch

Modified from Osborn AG: Diagnostic Cerebral Angiography. Lippincott Williams & Wilkins; 1999; and Hacein-Bey L, Daniels DL, Ulmer JL, et al: The ascending
pharyngeal artery: branches, anastomoses, and clinical significance. AJNR Am J Neuroradiol 23(7):1246-1256, 2002.
ECA, External carotid artery; ICA, internal carotid artery; ILT, inferolateral trunk; MMA, middle meningeal artery; VA, vertebral artery.

t­ ermination of contrast filling; sometimes meniscal endovascular procedures (Table 5-9). Moreover, it is of
filling defects also occur (Figure 5-14, A). Other angio- significance for planning a revascularization procedure
graphic abnormalities seen in acute cerebral infarction (e.g., carotid stenting) in patients presenting with TIA,
are slow anterograde flow with prolonged circulation time stroke, or symptoms of chronic cerebral hypoperfusion
and delayed arterial contrast “washout” in the affected area (Figure 5-48).
(contrast is still opacifying arteries in the early venous
phase of angiogram). Paucity of vessels (“bare areas”) Tumors
in nonperfused or slowly perfused brain may be seen in
some cases (Figure 5-14). Another common finding is Problem Solving: What Is the Role of DSA
the presence of pial-to-pial collaterals across the water- in Presurgical Evaluation of Intracranial and
shed zones with slow retrograde filling (into venous Extracranial Neoplasms?
phases) of patent but proximally occluded obstructed Noninvasive studies such as MRI have replaced cath-
branches. “Luxury perfusion” is a misnomer describing eter angiography in the evaluation of extracranial and
a prominent vascular blush that can sometimes be seen intracranial masses. Assessment of tumor vascularity or
within a few hours to days after stroke onset. Different involvement of large arteries, such as the ICA or ACA, or
mechanisms such as arteriolar–venular shunting and dural venous sinuses in surgical planning can be safely
capillary dilatation have been proposed for this incom- performed using noninvasive angiographic modali-
pletely understood phenomenon. In some cases, AV ties such as CTA/CTV or MRA/MRV. However, diagnos-
shunting with early draining veins in the ischemic focus tic angiography still may be required for presurgical
may be observed. Signs of mass effect are uncommon in evaluation of endovascular transarterial embolization
hyperacute stroke but may develop within the first week of tumor-­supplying arteries, as is typical for extraaxial
after stroke onset. masses supplied by meningeal branches of the ECA (i.e.,
Collateral circulation plays a crucial role in acute and middle meningeal artery branches in meningiomas). In
chronic cervical or intracranial arterial occlusion. The these cases, knowledge and visualization of potentially
understanding of collateral flow patterns (e.g., through dangerous collaterals between the ECA system and the
the circle of Willis, pial-to-pial, dural-to-pial, or extra- internal carotid or vertebrobasilar system is a crucial
cranial-to-intracranial anastomoses) is an ­important prerequisite. Another rare indication for performing
prerequisite for safe cerebral angiography as well as cerebral angiography in patients with intracranial mass
 Chapter 5 Diagnostic Angiography 265

SECTION II
A B

C D
Figure 5-48 Intracranial collateral flow patterns in a patient with right chronic right internal carotid artery (ICA) occlusion. A: Right common
carotid artery angiogram, lateral view, showing an occlusion of the cervical ICA just distal to the carotid bifurcation. The short vessel stump ends
in an rounded outpouching (large white arrow). No anterograde flow was seen on later phase images (not shown). Normal filling of the external
carotid artery (ECA) branches is noted. B: Right common carotid artery angiogram, lateral view of the cranial circulation, early arterial phase,
showing no filling of the intracranial ICA segments. Filling of the ECA branches is noted with multiple small dural-to-pial collaterals (black arrow-
heads) arising from branches of the middle meningeal artery as well as the accessory meningeal artery (small black arrow). C: Consecutive midarte-
rial phase showing delayed filling of multiple cortical branches (small black arrows) in the right middle cerebral artery (MCA) territory (M3 arteries)
via dural-to-pial collaterals. Again, no opacification of the right distal ICA and right proximal MCA is noted. D: Left vertebral artery angiogram,
lateral view, late arterial phase, showing opacification of the distal right anterior cerebral artery territory (distal pericallosal artery and branches,
small black arrows) via splenial and choroidal branches from the posterior cerebral artery (pial-to-pial collaterals). Faint collateral filling of the right
MCA (large white arrow) via the posterior communicating artery is depicted. (Courtesy Dr. Tejinder Pal Singh, Perth.)
266 Section II  Procedures

lesions is presurgical functional testing for eloquent periphery of the tumor may also be supplied by pial
brain (e.g., a Wada test). branches. Evaluation of the venous phase is crucial
General angiographic features of intracranial masses because growth into dural venous sinuses with ­secondary
reflect both their direct and indirect effects on intracra- occlusion is a typical phenomenon. Other tumors that
nial vessels. may be evaluated for presurgical planning or potential
Indirect manifestations of space-occupying lesions embolization include invasive skull base tumors such
include focal or generalized mass effect including as pituitary adenoma (uniform tumor blush), heman-
herniation syndromes. Small avascular extraaxial or gioblastoma (very intense vascular mural nodule), and
­intraaxial neoplasms can be easily overlooked on DSA. hemangiopericytoma (Figure 5-50).
When lesions become larger displacement of arterial Neovascularity (irregular and bizarre-appearing ves-
branches or cortical veins may occur. Cerebral hernia- sels, laking, pooling of contrast) is a common but not
tions are caused by gross mechanical displacement of entirely specific finding in primary malignant brain
brain, cerebrospinal fluid, and blood vessels from one tumors such as glioblastoma multiforme. Neoplastic
compartment to another. The patterns of herniation intratumoral AV shunts (early draining veins) are usu-
are classified according to which anatomic boundaries ally seen in high-grade gliomas and metastases. ­Vascular
the herniating structures cross: subfalcine, transtento- displacement or encasement is often seen in large skull
rial (ascending or descending), transalar, or tonsillar. base tumors such as pituitary adenoma, meningioma,
With larger masses, combinations of these syndromes and chordoma. Arterial occlusions and strokes are
can occur. Angiographically these syndromes cause uncommon manifestations of intracranial neoplasms.
classic patterns of vessel displacement (e.g., A2/A3 dis- Cortical vein occlusions or dural venous sinus invasion
placement underneath falx in subfalcine herniation). A classically occurs in extraaxial tumors such as menin-
detailed description of these characteristic patterns is gioma or dural metastasis.
beyond the scope of this chapter. The identification of A diagnostic angiogram may sometimes be obtained
these syndromes by catheter angiography has markedly in patients with extracranial/cervical neoplasms. Such
lost its diagnostic relevance over the last decades since neoplasms include juvenile nasopharyngeal angio-
CT and MRI have become standard modalities for evalu- fibroma (intense and prolonged vascular stain from
ating intracranial masses. However, the interventional internal maxillary artery branches), meningioma,
neuroradiologist should be familiar with their appear- schwannoma, and paraganglioma. The latter has a
ance because they may indirectly indicate mass effect strikingly similar angiographic appearance regard-
from expanding hematoma or hydrocephalus during less of location (glomus caroticum, glomus jugulare,
endovascular procedures. glomus tympanicum, glomus jugulotympanicum): a
The direct effects of mass lesions include arterial well-delineated round or lobulated vascular mass with
enlargement due to increased tumor supply, angiogen- dense, prolonged contrast staining is typical (cave: rare
esis with neovascularity, a tumor “blush,” blood–brain risk of hypertensive crisis precipitated by angiography
barrier disruption, intratumoral AV shunts, vascular in paragangliomas). AV shunts occur, glomus jugulare
encasement and occlusion, and rarely oncotic pseu- tumors typically occlude the jugular vein, and carotid
doaneurysms (see section on Indications/Aneurysms). body tumors splay apart the ECA and ICA. A detailed
A blush that is an accumulation of contrast during description of angiographic patterns of head and neck
the late arterial and early capillary phases of a cere- tumors and their mimics (reactive lymphadenopathy) is
bral angiogram is not pathognomonic for neoplasm. beyond the scope of this chapter.
It occurs normally in some relatively vascular areas Angiographic evaluation may be required in cases
such as the basal ganglia and simply reflects increased of difficult surgical access, skull base invasion, vascular
capillary density. An abnormal blush is a nonspecific encasement/invasion that requires larger vessel sacri-
finding that may occur with trauma, infection, cerebral fice (e.g., for temporary ICA balloon test occlusion), or
ischemia, and prolonged seizures. A spectrum of both for presurgical embolization in highly vascular lesions.
benign and malignant intracranial neoplasms dem- Delineating vascular supply and collateral vessels that
onstrates a prolonged vascular blush that represents include the identification of potentially dangerous col-
increased vessel density secondary to neoplastic vascu- lateral flow patterns (Figure 5-51 and Table 5-9) is essen-
lar proliferation. tial when performing and interpreting angiograms from
The most common tumor for which angiograms these patients.
are sometimes required to assess the possibility of pre-
surgical endovascular embolization is meningioma, Cerebrovascular Trauma
including all three histologic variants (benign, ­atypical,
and Dissection
anaplastic). Angiographically, most meningiomas are
highly vascular lesions that are supplied by multiple Problem Solving: What Different Types of Head
radiating vessels from hypertrophied meningeal arter- and Neck Vessel Injuries May Occur in Trauma?
ies (“sunburst pattern”), such as the middle meningeal What Circumstances Require a Cerebral
artery (Figure 5-49). A homogeneous prolonged tumor Angiogram in Patients with Sustained Head or
blush from late arterial to capillary phases is called the Neck Trauma?
mother-in-law sign: it comes early and stays late. ICA or Traumatic injury to the vessels of the head and neck can
VA angiograms often demonstrate only avascular mass result in potentially devastating neurologic sequelae.
effect due to a lack of pial supply. In larger lesions, the Because of the associated substantial morbidity and
 Chapter 5 Diagnostic Angiography 267

SECTION II
A B C

D E
Figure 5-49 T1-weighted magnetic resonance image postgadolinium, coronal view (A), showing large multilobulated bilateral parasagittal
extraaxial mass that is homogeneously contrast enhancing and involves the superior sagittal sinus, cranial vault, and overlying scalp. Right internal
carotid artery angiogram with late arterial (B) and venous (C) phase images, lateral view, show no relevant tumor supply from pial arteries but
avascular mass effect (white arrowheads in B) with stretching and draping of distal pial arteries. Segmental occlusion of the superior sagittal sinus
(white arrowheads in C) with draping of cortical veins is also demonstrated. D: Selective left external carotid artery angiogram, lateral view, late
arterial phase, showing an enlarged frontal branch of the middle meningeal artery (small black arrow) that supplies the dural-based tumor with a
typical “sunburst” tumor blush (large white arrow). Additional supply predominantly to the bony and scalp components is depicted from branches
of the superficial temporal artery (white arrowheads). E: Superselective angiogram from a microcatheter inserted into the frontal branch of middle
meningeal artery (small black arrow) again shows radial tumor blush (large white arrow) before presurgical embolization. A typical meningioma
was subsequently found after surgical resection. (Courtesy Dr. Constantine Phatouros, Perth.)
268 Section II  Procedures

A B

C
Figure 5-50 Left internal carotid artery angiogram, lateral view, early (A) and late (B) arterial phase, showing an irregularly configured, highly
vascular mass with pial supply from the pericallosal and callosomarginal arteries (small black arrows in A). The large tumor blush (large white arrows
in A and B) consists of multiple small “sunburst” vessels as well as bizarre-appearing vessels with pooling of contrast representing signs of neovas-
cularity. Additional meningeal feeders to the tumor are derived from an enlarged anterior falx artery (white arrowheads in A). C: Selective external
carotid angiogram, lateral view, showing further meningeal arterial supply to the tumor (large white arrow) from enlarged frontal branch of middle
meningeal artery (small black arrow). The patient underwent subsequent endovascular embolization of middle meningeal artery branches and pial
anterior cerebral artery branches. Surgical removal of a highly vascularized parasagittal extraaxial mass revealed a hemangiopericytoma. (Courtesy
Dr. William McAuliffe, Perth.)
 Chapter 5 Diagnostic Angiography 269

the vessel lumen, creating a flap or double lumen, or

SECTION II
through the adventitia outside the vessel wall.
Traumatic dissections typically involve both the cer-
vical and petrous parts of the ICA and spare the bulb.
The most common cause of traumatic ICA dissections
are motor vehicle accidents with associated hyperex-
tension/flexion injuries of the neck. VA dissections can
occur when the head is rotated in extension, leading to
stretching of the artery between C1 and C2, or can occur
due to direct vessel wall injury from a fracture of the
transverse foramen.
Although delayed cerebral ischemia is the most
frequently encountered clinical presentation, 20% to
33% of patients are clinically asymptomatic. Other
clinical presentations include carotodynia (i.e., neck
pain along the course of artery), headaches, Horner
syndrome, and cranial neuropathies. Spontaneous dis-
sections commonly show improvement or resolution
of stenotic lesions on follow-up angiography (85%
of cases). In contrast, traumatic dissections resolve or
improve in only 55%, while 25% progress to complete
occlusion.
Figure 5-51 Right external carotid artery angiogram, lateral pro- Conventional angiography has historically been
jection, illustrating a typical suboccipital craniocervical anastomosis considered the gold standard for dissection diagnosis.
between muscular branches of the occipital artery and vertebral artery The angiographic appearance of dissection is variable
at the level of C1 (so-called suboccipital Carrefour or knot). The V3 but often characteristic: smooth tapering of the ves-
segment of the right vertebral artery is transiently opacified with con-
trast (small black arrow). The patient has an arteriovenous malforma- sel lumen that may lead to an occlusion of the artery
tion (AVM) supplied by branches of the posterior cerebral artery. There (string sign); luminal stenosis that may or may not be
is evidence of faint filling of the vertebrobasilar system and the AVM followed by aneurysmal dilatation (pearl and string
(white arrowheads). This collateral pathway poses a significant poten- sign); or vessel wall irregularity. An intimal flap is only
tial risk for stroke in the vertebrobasilar territory when performing
neurointerventional embolization procedures.
rarely encountered on angiographic images (Figure
5-52). However, catheter angiography lacks assessment
of the vessel wall for intramural hematoma; therefore,
mortality, it is important to diagnose this rare compli- dissections in unusual locations or having atypical mor-
cation of head and neck trauma. The incidence of cere- phology may be misclassified or attributed to other pro-
bral vascular trauma ranges from 0.18% to 1.55% of all cesses. A combination of MRI/MRA and multidetector
trauma patients, with an approximate ratio of 2:1 for CT/CTA have emerged as viable alternatives for both
ICA involvement compared to VA involvement. Motor diagnosis and follow-up of dissection. In general, the
vehicle accidents account for the majority of these two techniques have different strengths and weaknesses.
lesions, and there is a male dominance with a mean age MRI is the ideal method for detecting acute infarction
less than 30 years in most series. A high risk of neurovas- or hemorrhage as possible sequelae of dissection. Axial
cular injury showed a strong tendency to be associated T1-weighted fat-suppressed images can detect the met-
with fractures of the sella turcica–sphenoid sinus com- hemoglobin of intramural hematoma within the false
plex. The two major pathomechanisms are penetrating lumen (crescent sign). Multidetector CT/CTA is faster
trauma and blunt trauma, with blunt trauma being by and more widely available, and it provides greater spa-
far the more common. For traumatic artery injuries, the tial resolution than MRI/MRA. Vertinsky et al. compared
three major anatomic substrates are dissections, pseu- both methods and slightly favored CT/CTA, particularly
doaneurysms, and AVFs. for VA dissections, because of visualization of more fea-
tures (e.g., intimal flaps, stenoses, pseudoaneurysms) in
Traumatic Arterial Injuries the affected ­arterial segment. Although the two, often
complementarily used, noninvasive modalities are the
Traumatic Cervical Artery Dissections preferred methods for diagnosis of dissection, conven-
Dissections account for the majority of cerebrovascular tional angiography may help in rare instances of confus-
trauma sequelae. An arterial dissection is defined as an ing or ambiguous cases.
intramural hematoma that might produce a stenosis
of the vessel, a luminal irregularity, and occasionally Traumatic Aneurysms
an aneurysmal dilatation. Most dissections are associ- Traumatic intracranial aneurysms are discussed in the
ated with an intimal defect if the dissection does not section on Indications/Aneurysms Traumatic extra-
arise from ruptured vasa vasorum. The intimal tear that cranial carotid (pseudo-)aneurysms may be the result
is associated with the primary injury may allow propa- of penetrating trauma or blunt trauma (e.g., rotatory
gation of circulating blood into the vessel wall. Further hyperextension, strangulation, fractures of the man-
distal, rerupture can occur through the intima into dibular angle). Extradural carotid aneurysms due to
270 Section II  Procedures

A B C

D E
F
Figure 5-52 Spectrum of traumatic dissections in three patients. Dissecting processes of the internal carotid artery can go along with vessel
wall irregularities (A, B), with a flap and double-lumen sign (C, F) or with an aneurysmal dilatation (D) that in this case spontaneously com-
pletely regressed on follow-up 3 months later (E). (From Krings T, Geibprasert S, Lasjaunias PL. Cerebrovascular trauma. Eur Radiol 2008;18:
1531-1545.)
 Chapter 5 Diagnostic Angiography 271

SECTION II
B
A
Figure 5-53 Traumatic carotid–cavernous fistula (CCF) following a motor vehicle accident. A: Lateral view of internal carotid artery (ICA)
angiogram. Direct filling of the ophthalmic vein via the cavernous sinus is the most frequently encountered venous drainage route. B: Antero-
posterior view of ICA angiogram at later phase filling of ophthalmic veins but also via the intercavernous sinus, contralateral cavernous sinus,
sphenoparietal veins bilaterally, and inferior petrosal sinus. (From Krings T, Geibprasert S, Lasjaunias PL. Cerebrovascular trauma. Eur Radiol
2008;18:1531-1545.)

­ enetrating injuries (more common) typically result

p may lead to devastating SAH. In cases of massive trauma,
from stabbing or gunshot wounds. Iatrogenic trauma the fistula may be associated with additional epistaxis
(following endarterectomy, tracheostomy, radical neck due to widespread laceration of the ICA.
dissection, intraoral surgery, biopsy of the middle ear DSA is regarded the method of choice for evalua-
mass in the presence of an intratympanic course of the tion of CCFs prior to treatment. Traumatic high-flow
carotid artery) also may cause such lesions. lesions require rapid frame rates as well as high-­contrast
­volumes and injection rates. In some cases with very
Traumatic AVFs rapid flow, the cavernous sinus is immediately opaci-
The most common traumatic AVFs are CCFs. They occur fied and the precise fistula point is obscured. Injec-
as a result of a tear in the ICA that is fixed within the tion of the contralateral ICA or a VA with temporary
cavernous sinus by fibrous trabeculae and small men- ipsilateral carotid artery compression may successfully
ingeal arteries. CCFs may be classified by cause (trau- demonstrate the site of fistulation. The route of venous
matic or spontaneous) or by flow velocity (high vs low). drainage affects prognosis and therefore requires ­careful
However, the most common classification is based on evaluation. Possible drainage routes are anteriorly via
arterial supply. Type A CCFs are direct shunts between the superior and inferior ophthalmic veins (the most
the cavernous sinus and the ICA. Indirect CCFs are dural frequently encountered route) (Figure 5-53), via the
fistulae between the cavernous sinus and dural branches superior and inferior petrosal sinuses, which usually
of the ICA (type B), the ECA (type C), or both (type connect to the transverse and sigmoid sinuses but may
D). Traumatic CCFs are almost always direct high-flow also have connections with the posterior fossa veins, via
fistulae between the ICA and the cavernous sinus (type the pterygoid plexus, via sylvian veins into cortical veins,
A). The typical etiology of such lesions is a skull base or via the basal vein of Rosenthal into the vein of Galen.
fracture; however, iatrogenic fistulae following tran­ Dangerous signs associated with increased morbidity
ssphenoidal surgery also might be encountered. or mortality include cortical or deep venous drainage,
Traumatic CCFs usually present a few days to a few associated pseudoaneurysms cavernous sinus varices,
weeks after injury. Typical clinical findings include and venous outflow obstruction.
immediate objective vascular bruit, pulsating exophthal- Traumatic AVFs other than CCFs are uncommon.
mos, and chemosis. Ophthalmoplegia is another com- Fistulae from the ECA constitute approximately 7% of
mon finding; it is caused by mass or pulsation effects head and neck AVFs, most commonly supplied from the
from the arterialized venous pouches. Blindness related middle meningeal and occipital arteries. Close spatial
to CCF always occurs with a delay following second- relation between the branches of the ECA and the emis-
ary glaucoma in which is related to venous congestion. sary veins in some areas of the skull may lead to an AVF
Delayed neurologic deficits due to intracranial venous secondary due to fractures. Such lesions can be classified
congestion and subsequent hemorrhagic events are into intracranially and extracranially draining fistulae.
exceedingly rare. If the venous pouches extend beyond The former, which are usually supplied by a meningeal
the cavernous sinus into the suprasellar region, ­rupture ECA branch, may demonstrate cortical venous drainage
272 Section II  Procedures

A B C
Figure 5-54 Representative findings of serial changes of the lesion in a case of anterior cerebral artery (A2 segment) dissection. A: Angio-
gram of the right carotid artery, oblique view, obtained at admission, showing mild stenosis accompanied by double lumen (arrowheads) at A2.
B: Angiogram of the right carotid artery, oblique view, showing progression to severe stenosis (closed arrowheads) with aneurysmal dilation (open
arrowhead) 2 weeks after onset. C: Angiogram of the right carotid artery, oblique view, showing resolution 5 months after onset (arrowheads).
(From Ohkuma H, Suzuki S, Kikkawa T, Shimamura N. Neuroradiologic and clinical features of arterial dissection of the anterior cerebral artery.
AJNR Am J Neuroradiol 2003;24:691-699.)

(risk of hemorrhage), drain into the cavernous sinus years). Headache is a common prodrome and present-
(mistaken for CCF), or manifest with a sole diploic or ing symptom. Neurologic deficits are caused by isch-
dural drainage. Extracranially draining AVFs typically emia or stroke, are due to stenosis or occlusion, or are
present with a pulsatile mass, a bruit, or cranial nerve the result of SAH. SAH due to rupture of a dissecting
deficit depending on the location of the fistula (most aneurysm is believed to occur in 1% to 10% of patients.
commonly cranial nerve XII). Traumatic AVFs affecting In some cases, a (minor) trauma preceding dissection is
the VA are 10 times less common than CCFs and are found. Many predisposing factors including hyperten-
constituted by an abnormal communication between sion and fibromuscular dysplasia have been proposed,
the extracranial VA or its muscular branches and the sur- but often no history of trauma and no underlying dis-
rounding venous plexuses. Clinical symptoms are pulsa- ease can be identified.
tile tinnitus or a cervical bruit (present each in 30%–40% On DSA, the only pathognomonic finding suggest-
of patients). Enlarged venous pouches may cause myelo- ing a dissection—the double-lumen appearance with
radiculopathy or even quadriparesis. Blurred vision an intimal flap—is rarely encountered in intracranial
resulting from posterior fossa venous congestion is rare dissections. The presence of the “pearl and string sign”
and indicates emergency treatment. In rare instances, (i.e., focal narrowing with a distal site of dilatation) is
reflux into the spinal perimedullary veins leads to pro- considered a reliable sign. In contrast, the string sign
gressive congestive myelopathy. Neck or facial pain and and tapered narrowing are less reliable signs because
a torticollis may be present. Symptoms of posterior cir- these changes might also be seen in arteriosclerotic
culation TIAs, lower cranial nerves deficit, and decreased ­disease and in the presence of vasospasm. Serial changes
distal pulse of the ipsilateral upper extremity may point of angiographic findings are often seen during follow-
to a steal phenomenon of a VA fistula. up angiograms and reflect the dynamic nature of a
­dissection (Figure 5-54). The vast majority of spontane-
Intracranial Dissection ous intracranial dissections are found in the posterior
circulation, most commonly involving the V4 segment
Not long ago intracranial dissection was considered as of the VA. Bilateral involvement as well as extension
an extremely rare disease, but it has become increas- of an extracranial to an intracranial dissection are not
ingly recognized. Clinicopathologically it can be clas- uncommon. Dissection might also occur in the ICA,
sified into two categories: (1) dissections between the MCA, or ACA.
intima and media, causing luminal narrowing or ste- Besides visualization of the sequela of intracranial
nosis (simply termed dissections); and (2) dissections dissection (e.g., stroke, hemorrhage), CT/CTA and MRI/
between the media and adventitia, or at the media, MRA are capable of raising the suspicion or definitively
causing aneurysmal dilatation (termed dissecting aneu- establishing the diagnosis of intracranial dissection in
rysms). The mean age of onset is 51 years (range 8–86 many cases. For recognition of intracranial dissection,
 Chapter 5 Diagnostic Angiography 273

these modalities require use of an additional feature: Brinjikji W, Cloft H, Lanzino G, Kallmes DF. Comparison of 2D digital

SECTION II
subtraction angiography and 3D rotational angiography in the evaluation
direct assessment of the vessel wall. Chen et al. reported of dome-to-neck ratio. AJNR Am J Neuroradiol. 2009;30:831-834.
a high diagnostic accuracy (98.5%) of CTA in detect- Britt PM, Heiserman JE, Snider RM, Shill HA, Bird CR, Wallace RC. Incidence
ing intracranial VA dissections. The principal findings of postangiographic abnormalities revealed by diffusion-weighted MR
imaging. AJNR Am J Neuroradiol. 2000;21:55-59.
are increased external arterial diameter (100%) and a Broderick JP, Brown Jr RD, Sauerbeck L, et al. Greater rupture risk for familial
crescent-shaped mural thickening (79%). However, dif- as compared to sporadic unruptured intracranial aneurysms. Stroke.
2009;40:1952-1957.
ferentiating an intramural hematoma in an occluded Brouwer PA, Bosman T, van Walderveen MA, Krings T, Leroux AA, Willems PW.
dissection from a mural thrombus in an occluded vessel Dynamic 320-section CT angiography in cranial arteriovenous shunting
may not be possible. On TOF MRA, suppression of flow lesions. AJNR Am J Neuroradiol. 2010;31:767-770.
Brown Jr RD, Huston J, Hornung R, et al. Screening for brain aneurysm in the
signal in venous plexus surrounding the arteries can be Familial Intracranial Aneurysm study: Frequency and predictors of lesion
problematic and limiting. Direct visualization of intra- detection. J Neurosurg. 2008;108:1132-1138.
mural hematoma on T1-weighted MRI is incomplete at Buhk JH, Wellmer A, Knauth M. Late in-stent thrombosis following carotid
angioplasty and stenting. Neurology. 2006;66:1594-1596.
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SECTION II
unruptured brain arteriovenous malformations is experimental therapy. cerebral aneurysms, part I: MR angiographic follow-up of coiled aneurysms.
Curr Opin Neurol. 2006;19:63-68. AJNR Am J Neuroradiol. 2007;28:1001-1008.
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malformation: Time-resolved contrast-enhanced MR angiography with cerebral aneurysms, Part II: CT angiographic follow-up of surgically clipped
combination of parallel imaging, keyhole acquisition, and k-space sampling aneurysms. AJNR Am J Neuroradiol. 2007;28:1207-1212.
techniques at 1.5 T. Radiology. 2008;246:871-879. Wermer MJ, Rinkel GJ, van Gijn J. Repeated screening for intracranial aneurysms
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 chapter 6

Neurointerventional Radiology
Ruth Thiex, Ajit Puri, and Darren B. Orbach

BRIEF HISTORICAL BACKGROUND

are ­navigated using a combination of torquability and
Therapeutic endovascular occlusion predates Egas blood flow, guidewire-directed microcatheters such as
Moniz’s development of cerebral angiography and was the Prowler (Codman & Shurtleff, Inc., Raynham, MA),
first described in 1904 by James Dawbarn, a general Excelsior SL-10 (Boston Scientific), and Echelon micro-
surgeon, who injected liquid paraffin into surgically catheters (ev3, Irvine, CA), are manually advanced over
exposed external carotid artery branches in malignant a guidewire. Safer access, refined embolic agents, and a
head and neck tumors. In 1930, Brooks et al. intro- better understanding of functional anatomy all devel-
duced a piece of muscle into the internal carotid artery oped in tandem, allowing explosive growth of endovas-
to treat a traumatic cavernous carotid fistula. In 1960, cular options.
Luessenhop and Spence described embolization of The introduction of novel liquid embolic agents,
brain arteriovenous malformations (AVMs) by open such as N-butyl cyanoacrylate (NBCA, Trufill Liquid
arteriotomy of the carotid artery followed by intro- Embolic, Cordis Corp.) and Onyx (ev3), enhanced the
duction of small emboli (pellets), initially handmade endovascular treatment of AVMs tremendously. Since
methacrylate spheres and later silicone, that preferen- the introduction of electrolytically detachable platinum
tially made their way into the AVM via passive flow. coils by Guglielmi, a plethora of coils from numerous
Improvements in the efficacy and safety of brain AVM manufacturers has evolved. Attempts to address broad-
embolization were made by Djindjian et al., Kricheff et necked aneurysms, atherosclerotic stenosis, and arte-
al., Wolpert and Stein, and Doppman et al. in the late rial dissections brought self-expanding stents into play.
1960s and 1970s. A few years later, Zanetti and Sher- Higher-coverage stents currently are under active devel-
man introduced cyanoacrylate as an adhesive embolic opment in attempts to achieve arterial flow redirection,
agent. resulting in true endovascular reconstruction of a more
In the 1960s and early 1970s, Serbinenko developed optimal arterial lumen.
a nondetachable, flow-directed balloon that was used The pioneering spirit of the early innovators, together
for selective catheterization of circle of Willis branches. with the remarkable technologic achievements of the
He described using his balloons for treating cavernous past two decades in both materials and imaging, has
carotid fistulae while preserving the parent internal allowed the field of neurointerventional radiology to
carotid artery, and he proposed using balloon occlusion progress in quantum steps over a remarkably short
for treatment of saccular aneurysms of cerebral arteries. period of time.
For many years, balloon techniques remained the only
option for treatment of endovascular aneurysm occlu- CEREBRAL ANEURYSMS
sion.
In the 1980s, tremendous technical innovation Background
occurred in materials science and design, with the
variable stiffness microcatheter that tremendously Guido Guglielmi and Ivan Sepetka’s development of the
improved the utility, efficacy, and safety of superselec- detachable platinum coil in 1991 profoundly changed
tive intracranial angiography. In 1986, Target Thera- aneurysm therapy, and coil technology continues to
peutics introduced their tracker microcatheter and evolve. Subsequent developments have included the
associated microguide wire (Boston Scientific/Target, balloon remodeling technique introduced by Moret et
Fremont, CA), allowing controlled navigation that al. to provide a scaffold at the aneurysm neck, allow-
was less dependent on the influence of blood flow ing coiling of wider-necked aneurysms, and the devel-
and vascular geometry. In the following years, a pan- opment of three-dimensional coil shapes. “Bioactive”
oply of microcatheters became available, with refined coated coils, designed to promote aneurysm occlusion
properties (braided walls, surface coatings) optimized via scarring and thrombosis, have yet to convincingly
for specific anatomic configurations. Flow-guided demonstrate superiority over bare metal coils. The
microcatheters, such as the Magic (Boston Scientific), introduction of stent technology allowed for endovas-
are designed with a proximal shaft for support and cular treatment of even more wide-necked aneurysms
pushability, a supple midshaft, and an extra supple than was previously feasible. Current clinical research
1.2F, 1.5F, or 1.8F shapeable distal segment for flow- is focused on ­modifications in stent structure, strut
guided catheterization. Whereas these microcatheters diameter, and configuration to sufficiently redirect flow,

276
 Chapter 6 Neurointerventional Radiology 277

lessen shear stress, and result in aneurysm healing. The balloon occlusion over proximal surgical ligation was

SECTION II
Pipeline embolization device (Chestnut Medical, Menlo the possibility of delivering the balloon adjacent to
Park, CA), a flexible, self-expanding stent with dense the aneurysm itself, trapping the neck both proximally
strut coverage, is the first device clinically available in and distally, thereby preventing backflow and refilling.
the United States explicitly designed to achieve primary Another significant advantage was that balloon occlu-
parent vessel reconstruction rather than endosaccular sion can be performed on an awake patient, allow-
occlusion as a means of aneurysm treatment. ing continuous neurologic assessment during balloon
test occlusion, prior to permanent vessel sacrifice. In
How Were Intracranial Aneurysms Originally addition, collateral arterial supply can be evaluated
Approached Endovascularly? angiographically at the time of balloon test occlusion
Permanent exclusion of cerebral aneurysms from the (Figure 6-2).
circulation is the main goal of therapy. Endovascu- The predictive value of balloon test occlusion can be
lar obliteration techniques can be divided into parent enhanced by qualitative cerebral blood flow imaging by
artery occlusion with or without preceding bypass pro- technetium-99m (99mTc) single-photon emission com-
cedure (deconstruction), and endosaccular occlusion puted tomographic scanning, where the tracer (typi-
of the aneurysm, with preservation of the parent vessel cally hexamethylpropyleneamine oxime [HMPAO]) is
(reconstruction). injected following balloon inflation and vascular occlu-
Deconstruction, or parent vessel occlusion, either sion. Hemispheric asymmetries and reductions in tracer
surgical or endovascular, continues to be used to treat uptake have been shown to correlate with the develop-
aneurysms such as nonreconstructable cavernous/ ment of neurologic deficits. In cases of failed balloon
petrous/extracranial internal carotid artery aneurysms, test occlusion, a bypass graft procedure is required
extracranial vertebral artery aneurysms, dissecting aneu- before permanent vessel occlusion. Conversely, if bal-
rysms of the internal carotid artery/vertebral artery, fusi- loon test occlusion is uneventful, permanent vessel sac-
form aneurysms without a well-defined neck, and giant rifice is performed.
saccular aneurysms with an ill-defined neck or inacces-
sible location. What Are Potential Risks of Detachable
Surgical ligation of the parent vessel for aneurysms Balloons?
in surgically inaccessible locations was more common Although detachable balloons achieve immediate flow
before endovascular approaches were devised, but they arrest and overall reduction in procedure time, they har-
can be associated with high ischemic stroke morbid- bor the following risks: incomplete obliteration of the
ity and mortality (Figure 6-1). With the development aneurysm due to fixed, predetermined balloon shape,
of detachable balloons, the possibility of endovascular aneurysm rupture due to wall distension by the bal-
parent artery occlusion for aneurysm treatment became loon or due to other maneuvers during balloon place-
a reality. The most significant advantage of ­endovascular ment, premature detachment of the partially inflated

Figure 6-1 Lateral views of a left common carotid artery injection, subtracted (left) and unsubtracted (right). The subtracted view shows a
middle cerebral artery branch dissecting aneurysm. The unsubtracted view shows parent artery exclusion using surgical clips.
278 Section II  Procedures

or deflated balloon, and thrombus ­formation, in cases aneurysm. A radial artery line is often placed for con-
where the balloon partially projects into the parent ves- tinuous monitoring of the arterial blood pressure; this
sel (particularly in broad-necked aneurysms). line also facilitates blood draws for measurement of
the activated clotting time (ACT). In elective aneurysm
How Can Endovascular Obliteration of the coiling, systemic heparinization (ACT target 250–300
Aneurysm Alone be Achieved? seconds) is initiated after groin access. In many centers,
The ideal reconstructive goal for intracranial saccular for cases of acute subarachnoid hemorrhage, anticoagu-
aneurysm treatment is to occlude the aneurysm itself lation with intravenous (IV) heparin is begun after the
while maintaining parent vessel patency. In 1982, first coil is placed, although practice patterns are quite
Romodanov and Shchegelov first reported the use varied in this regard. Preliminary angiographic evalu-
of a detachable balloon for occlusion of intracranial ation is made with standard frontal and lateral views.
aneurysms while maintaining parent vessel patency. Three-dimensional angiographic reconstructions facili-
However, the definitive breakthrough was Guido Gug- tate accurate measurement of aneurysm dimensions,
lielmi’s development of the electrolytically detachable identification of perforating vessels originating within
coil system for aneurysm treatment, which has revo- the aneurysm region, and selection of the best work-
lutionized the endovascular approach to aneurysm ing projection for embolization (Figure 6-3). In addi-
management. tion to aneurysm size and orientation, the relationship
Both aneurysm size and neck morphology play criti- between the aneurysm neck and dome and between the
cal roles in successful obliteration of the lesion. A num- neck and the parent artery, as well as the morphology
ber of methods have been reported to measure the size of the parent artery are evaluated. A roadmap image
of the aneurysm neck, but the neck typically is catego- of the parent vessel and aneurysm is obtained in the
rized as small if it measures ≤4 mm and broad if >4 mm. best working projection. A microcatheter with two sets
This distinction is important because it is technically of markers (at the tip and 3 cm proximal to the tip) is
difficult to pack broad-necked aneurysms without the coaxially advanced into the aneurysm fundus with the
risk of coils prolapsing into the parent vessel, whereas a aid of a microguide wire. The coaxial catheter system is
small neck more readily retains the occlusive coils. continuously flushed with heparinized saline to lower
the risk of thrombus formation. Once the microcatheter
What Is the General Method of Coiling
Aneurysms?
General anesthesia is used at most centers to ensure
more controlled patient management, better imaging
quality, and safer superselective catheterization of the

Figure 6-2 Lateral unsubtracted view of a balloon test occlusion.

The balloon (dashed arrow) is inflated in the external carotid artery, Figure 6-3 Top: Three-dimensional reconstruction from a rota-
which is supplying a portion of the middle cerebral artery territory via tional angiographic run demonstrating an internal carotid artery aneu-
a surgical bypass. The guide catheter in the external carotid is shown rysm (patient had presented with massive epistaxis due to herniation
with the solid arrow. The dotted arrow points to a diagnostic catheter of aneurysm into sphenoid sinus). The narrow neck of the aneurysm,
in the ipsilateral internal carotid artery, through which contrast was a favorable configuration for coil retention, is clearly seen. Bottom:
injected to perform the angiogram. Progressive packing of the aneurysm volume with detachable coils.
 Chapter 6 Neurointerventional Radiology 279

is ­properly positioned within the aneurysm, a detach- Problem Solving Unfavorable Aneurysm

SECTION II
able coil is introduced via the microcatheter. When the Geometry: What Are Assist Techniques
marker on the delivery mandrel overlaps the proximal and Some Limitations of Aneurysm Coiling?
platinum marker on the microcatheter, the detachment One of the most common technical limitations of coil
zone is 2 to 3 mm beyond the tip of the catheter. If coil embolization of aneurysms involves the geometry of
position is deemed satisfactory, the coil is detached the aneurysm neck. If the ratio of dome size to neck
using either an electrolytic or mechanical system. Com- size is not favorable (usually ratio <2) or the neck itself
plete detachment is tested by gently retracting the deliv- is very wide (usually >4 mm), the neck will not act as
ery wire under fluoroscopy while verifying that the coil a buttress for the coil mass, and the coils will tend to
remains in place. herniate into the parent artery. Several strategies, all of
Most commonly, the first coil deployed is one that which are called assist techniques, have been developed
takes on a three-dimensional shape as it extrudes from for facing this challenge. Most (but not all) studies
the microcatheter (as opposed to helical coils, which describe an increased complication rate from embo-
typically are referred to as “2D”). The three-dimen- lization using assist techniques compared to straight-
sional shape of this initial “framing” coil generates a forward coiling. However, a higher complication rate
coil basket within the aneurysm fundus, with one or a could arise not from the complexity of the techniques
few loops of coil preferably bridging the neck. This bas- themselves but from the fact that the underlying aneu-
ket is the structure within which further coils will be rysms requiring such techniques are inherently more
packed, as the aneurysm volume is progressively filled dangerous to treat.
(Figure 6-3). The goal of endovascular embolization Moret and colleagues described the first assist tech-
is complete angiographic obliteration of the fundus, nique, that of “remodeling,” in which two microcatheters
although quantitative analysis reveals that even with no rather than one are navigated to the aneurysm ostium,
visible angiographic remnant after coiling, at best only one to deploy the coils and the other a balloon micro-
30% to 40% volumetric occlusion is achievable. After catheter. The microballoon is inflated at the aneurysm
embolization, the microcatheter is slowly removed neck during the deployment of each coil, creating a
from the aneurysm and a postembolization angiogram temporary scaffold upon which the loops of the coil
performed to assess the final outcome and patency of can form their three-dimensional shape without par-
the parent vessel. ent vessel herniation (Figure 6-4). For balloon-assisted
The platinum coil system is a safe and effective treat- embolization, a potential source of complications is
ment option. The suppleness and flexibility of plati- the induction of stasis of blood in the parent artery
num coils allow occlusion of the aneurysm without during balloon inflation, which increases the tendency
undue stress on the wall and thus has demonstrated for thrombi to form and potentially cause ischemia. In
efficacy both for unruptured and ruptured aneu- order to lower this risk, balloon remodeling is carried
rysms. Early treatment of ruptured aneurysms caus- out with the patient fully anticoagulated. Some practi-
ing subarachnoid hemorrhage both reduces the risk tioners are reluctant to anticoagulate a patient with an
of rebleeding and facilitates the initiation of aggres- acutely ruptured aneurysm before treatment has started,
sive management of vasospasm and raised intracranial so in those centers, balloon remodeling is used only in
pressure. the setting of embolization of unruptured aneurysms.

Figure 6-4 Oblique unsubtracted views of balloon-assisted coiling of a cerebral aneurysm. Left: Inflated balloon seen en face, with the coil mass
seemingly hovering over it. Right: Scaffold proved by the balloon allows progressive coiling of the aneurysm neck, eliminating the “hovering coil
mass” effect. The patient had a large wide-necked contralateral aneurysm as well coiled using stent assistance. Markers at each end of the stent are
delineated by the white arrows. (Courtesy Dr. Peter K. Nelson, NYU Medical Center.)
280 Section II  Procedures

Flexible, self-expanding nitinol stents have become effect or arterial pulsation force on adjacent structures,
increasingly important in the treatment of wide-necked such as cranial nerves. Long-standing cranial neuropa-
aneurysms. The stent is deployed in the parent vessel thies resulting from compression by a large aneurysm
across the ostium of the aneurysm and acts as a baffle to are unlikely to improve, whether treated by surgical
prevent coil herniation. The coil microcatheter is navi- clipping or by coiling. However, short-term cranial neu-
gated through the struts of the stent into the aneurysm, ropathies may reverse, although it has proven difficult
and the coils are deployed. Alternatively, the coil micro- to predict which aneurysms will respond as well to coil
catheter is first introduced into the aneurysm without embolization (which does not ameliorate mass effect)
deployment of coils, the stent is placed, trapping the as to surgical clipping.
coil microcatheter against the vessel wall, and then the Finally, endovascular embolization may be severely
aneurysm is coiled and the coil microcatheter removed. limited in cases where the aneurysm incorporates parent
In the United States, the two stents most commonly branch vessels into its neck. Although a skilled surgeon
used for this purpose are the Neuroform (Boston Sci- may create a clip construct that maintains the patency of
entific/Target) and the Enterprise (Cordis, Blooming- such branches while excluding the aneurysm dome, for
ton, IN). Stent-assisted aneurysm embolization can be certain aneurysm geometries no endovascular analogues
undertaken either in a single procedure or as a staged currently are available.
procedure, with the stent deployed first and allowed to
set into the endothelium for several weeks, after which What Are the Complications of Aneurysm
the patient undergoes a second procedure for aneurysm Coiling?
coiling. Just as aneurysm rupture may complicate surgical clip-
Arterial stents are highly thrombogenic after initial ping, perforation during embolization may occur and is
deployment, until they have undergone a period of endo- reported in 2% to 4% of cases, with a higher incidence
thelialization over several weeks to months. Thus, deploy- in recently ruptured and in small aneurysms (Figure
ment of a stent without pretreatment with a regimen of 6-5). The cause can be related to fragility of the aneu-
antiplatelet medications (typically two oral agents, such rysm wall, microcatheter instability during coil deploy-
as clopidogrel and aspirin, given for at least 3 days) ment, or incompatibility between the coil geometry and
would entail a high risk of in situ thrombus formation the aneurysm. Asymptomatic rupture, usually caused
and potential embolization. Thus, stent-assisted coiling by herniation of the microwire, may be suspected only
is most straightforward in the setting of elective treatment because of contrast extravasation outside the previously
of unruptured aneurysms. In cases where pretreatment defined aneurysm luminal contour. Symptomatic rup-
with antiplatelet agents was not possible, a loading dose ture, usually resulting from perforation by coils or by
of antiplatelet agent can be administered intravenously the microcatheter, may cause an immediate spike in
and continued until oral agents have reached therapeu- intracranial pressure, with accompanying hypertensive
tic serum concentration. Although stent-assisted coiling bradycardia or even asystole. If rupture is suspected, anti-
is performed at some centers in cases of ruptured aneu- coagulation is immediately reversed using protamine
rysms, both the thrombotic risks (which are particularly sulfate, and embolization should proceed as rapidly as
increased in the setting of subarachnoid hemorrhage) possible. If available, a balloon may be inflated in the
and the hemorrhagic risks from antiplatelet medication parent vessel to staunch the subarachnoid hemorrhage.
(particularly in the setting of the potential need for pro- If not already in place, immediate external ventricular
cedures such as ventriculostomy) are high. drainage should be considered.
In addition to the risk of rupture, giant intracranial Thromboembolic complications are reported to
aneurysms potentially cause symptoms related to mass occur in approximately 3% of aneurysm embolizations,

Figure 6-5 First panel: Oblique view of right internal carotid artery communicating segment aneurysm. Second panel: Unsubtracted view
during coil embolization demonstrating perforation of the aneurysm by a coil loop, which is seen to protrude beyond the contour of the aneu-
rysm seen in the first panel (white arrow). Third panel: Subtracted view demonstrating contrast extravasation into the subarachnoid space (white
arrow), consistent with intraprocedural aneurysm rupture. The patient’s heart rate immediately fell and the blood pressure rose. Fourth panel: The
aneurysm was rapidly coiled to completion, with no residual filling of the dome. The patient made an uneventful recovery.
 Chapter 6 Neurointerventional Radiology 281

with permanent neurologic disability reported in 1.7% reversible ischemic injury, intracranial vessel status, and

SECTION II
to 5% of procedures. Thrombus formation at the aneu- possibly the volume of already infarcted tissue. A mul-
rysm neck during or immediately after embolization is timodal magnetic resonance imaging (MRI) approach
the likely cause of many such events. Potential etiologies includes magnetic resonance angiography (MRA), diffu-
include (1) the hemodynamic effects of the guide cath- sion-weighted imaging, and perfusion-weighted imag-
eter in the parent artery slowing flow, possibly due to ing. Diffusion-weighted imaging allows visualization
vasospasm, (2) thrombus formation on the microcath- of ischemic regions within minutes of symptom onset
eter or coil mass, (3) stenosis of the parent artery due and early identification of lesion size, site, and age. The
to protrusion of the coil mass, and (4) displacement of ischemic penumbra is approximated on MRI as regions
intraaneurysmal thrombus during embolization. Rare of perfusion change without a corresponding diffusion
causes of thromboembolism are hypercoagulable states, abnormality (diffusion–perfusion mismatch). Multi-
such as antiphospholipid syndrome. parametric MRI criteria to differentiate regions with
Although aneurysm embolization is almost always irreversible infarction from regions with potentially
performed with anticoagulation, lysis of formed throm- reversible ischemia are under investigation.
bus typically requires additional administration of IV The major risk of thrombolytic treatment in the
antiplatelet agents such as the IIb/IIIa receptor binders NINDS trial was symptomatic intracerebral hemorrhage,
abciximab or eptifibatide. In unruptured cases, fibri- which increased 10-fold in treated patients compared
nolytic agents such as urokinase or recombinant tissue with placebo (6.4% vs 0.6%, respectively). Trials of IV
plasminogen activator (r-tPA) can be used for emboli- r-tPA that included an angiographic component have
zation-related thromboembolism, but their use in the demonstrated that the rate of recanalization of large-
setting of subarachnoid hemorrhage is fraught with risk. vessel arterial occlusions with IV r-tPA is low, with par-
tial or complete recanalization of only 10% of occluded
ACUTE STROKE internal carotid arteries and 25% of occluded proximal
MCAs. Therefore, an intraarterial (IA) approach in order
Historical Background to deliver the thrombolytic agent in a high concentra-
tion directly into the thrombus has been promoted.
A new era in acute stroke therapy began with publica- More detailed schemes for assessing the initial angio-
tion of the prospective National Institutes of Neuro- graphic data, accounting both for site of occlusion and
logical Disorders and Stroke (NINDS) trial, which was identification of collateral supply, have been developed
completed in 1995. The study, which led to United in order to stratify patients by the expected rate of recan-
States Food and Drug Administration (FDA) approval of alization and short-term outcome after IA thrombolysis.
tPA for acute ischemic stroke, found that patients treated
with IV tPA within 3 hours of symptom onset had a sub- What Are the Benefits of IA Thrombolysis?
stantially better chance of achieving functional indepen- IA thrombolysis allows extension of the treatment time
dence, with minimal or no disability at 3 months, than window, delivery of a higher concentration of lytic agent
did those given placebo. Additional trials of thromboly- to the target thrombus with lower systemic exposure,
sis for acute stroke followed, and a pooled analysis of higher recanalization rates, the potential for salvage
all 2,775 patients enrolled in the first six IV r-tPA trials therapy for IV r-tPA nonresponders, and combined ther-
demonstrated clear and convincing evidence of a time- apy with other endovascular techniques. The potential
dependent benefit of thrombolytic therapy. Treatment benefits of IA lysis were demonstrated early in the Pro-
within the first 90 minutes of symptom onset increased lyse in Acute Cerebral Thromboembolism II (PROACT
the odds of a favorable outcome by 2.8-fold, whereas II) trial, in which 40% of the 121 subjects treated intra-
treatment in the 91- to 180-minute window increased arterially with the lytic prourokinase within 6 hours of
the odds by 1.6-fold. symptom onset had a good neurologic outcome (modi-
Given the narrow therapeutic window for IV treat- fied Rankin score 0–2) at 3 months, compared to 25%
ment of acute ischemic stroke, timely evaluation and of the 59 subjects who did not receive IA lytic. How-
diagnosis of ischemic stroke are paramount. Noncon- ever, IA thrombolysis requires additional time to initi-
trast brain-computed tomography (CT) is the minimum ate therapy, is available only at specialized centers, and
CT imaging requirement before proceeding with lytic involves the risk of potential arterial injury from endo-
therapy, with any intracerebral hemorrhage serving as vascular manipulation.
an absolute contraindication to thrombolysis. The his- Numerous mechanical devices have been used for
tory, physical examination, and laboratory exclusion thrombus extraction and maceration, offering the poten-
criteria are listed in the guidelines for the early man- tial of quick recanalization even in the setting of large
agement of adults with ischemic stroke. Early signs of clot burden (Figure 6-6). The two FDA-approved devices
major infarction on initial CT scan (e.g., mass effect, are the mechanical embolus retrieval in cerebral isch-
edema, hypodensity involving more than one third of emia (MERCI, Concentric Medical, Inc., Mountain View,
the middle cerebral artery [MCA] territory) are reasons CA) system and the Penumbra system (Penumbra, Inc.,
for caution in the use of thrombolytic therapy because Alameda, CA), described later, but other techniques, such
of the increased risk of hemorrhage. More sophisti- as balloon angioplasty and stenting, also can be used.
cated multimodal approaches to acute stroke imag- However, an IA lytic, deliverable via the most flexible
ing include perfusion CT and CT angiography, which and diminutive microcatheters, still offers the advantage
provide information about the degree of potentially of addressing smaller occlusions in ­distal arteries not
282 Section II  Procedures

Figure 6-6 Two patients with acute ischemic stroke due to right distal internal carotid and proximal middle cerebral artery occlusion, who
presented within several hours of each other. Top: This patient was not a candidate for intravenous tissue plasminogen activator (IV tPA) but had
a mechanical thrombectomy with the mechanical embolus retrieval in cerebral ischemia (MERCI) device. The patient had an excellent clinical
outcome (follow-up computed tomographic scans shown on the right). Bottom: This patient did receive IV tPA but could not undergo mechanical
thrombectomy because of lack of arterial access. The patient had a poor clinical outcome, with a devastating infarct (follow-up computed tomo-
graphic scans shown on the right).

amenable to mechanical techniques. The Interventional s­ ignificant neurologic improvement, have radiographic
Management of Stroke (IMS) I and II pilot trials demon- evidence of occlusion of an angiographically approach-
strated potential utility in combining IV thrombolysis able vessel (internal carotid artery, MCA M1 or M2 seg-
and its advantages (speed of initiation and widespread ment, vertebral artery, or basilar artery), and have the
availability) with IA techniques for recanalization and potential for delivery of thrombolytic within 6 hours
their advantages (concentrated local dosing, mechanical of symptom onset. Primary IA thrombolysis is per-
techniques for recanalization, and higher rates of recan- formed if patients present after 3 hours from symptom
alization) for the treatment of moderate-to-large strokes onset (i.e., outside the IV window) or had contraindi-
(National Institutes of Health Stroke Scale [NIHSS] score cations to IV tPA (e.g., recent history of major surgical
≥10). Moreover, the safety profile for such combined procedures). CT exclusion criteria are the same as for
treatment was similar to that of IV tPA alone. Numerous IV therapy: hemorrhage of any degree or location, sig-
other trials of mechanical and combined mechanical nificant mass effect with midline shift, parenchymal
and lytic therapy have been performed, with additional hypodensity consistent with ischemic change in a large
trials underway. It is our practice, and that of many other cortical volume (usually greater than one third of the
centers, to administer IA pharmacolysis whenever pos- MCA territory), and the presence of intracranial tumors
sible, even in cases where mechanical thrombectomy is other than small meningiomas. Potential angiographic
attempted. This is done both to increase the efficacy of exclusion criteria are arterial dissection or stenosis pre-
mechanical thrombus disruption and extraction and to cluding safe microcatheter access to the target vessel or
lyse potential small emboli that are dislodged distally a nonatheromatous arteriopathy, which may increase
in the course of extraction (Figure 6-7). At other centers, the risk of inducing hemorrhage with endovascular
however, mechanical thrombectomy is performed with- manipulation.
out pharmacolysis, with the idea of lessening the risk of
hemorrhagic conversion. How Is IA Thrombolysis Carried Out?
It is our practice and that at many centers, to perform IA
What Are Inclusion and Exclusion Criteria thrombolysis under general anesthesia in order to lower
for IA Thrombolysis? the risk of vessel injury from movement during endo-
At most centers, IA thrombolysis is considered if vascular manipulation. At centers where thrombolysis
patients treated with IV r-tPA have experienced no is performed without general anesthesia, the patient’s
 Chapter 6 Neurointerventional Radiology 283

SECTION II
Figure 6-7 Intraarterial thrombolysis in the setting of acute ischemic stroke. Upper left panel: Nonopacification of the internal carotid artery
(ICA) terminus, M1 segment, and A2 segment, consistent with at least two thrombus fragments. Upper right panel: After intraarterial administra-
tion of tissue plasminogen activator, recanalization of the ICA terminus, anterior cerebral artery, and inferior division of the middle cerebral artery
(MCA), with some filling of the M1 segment, is seen. Lower left panel: After one pass of the mechanical embolus retrieval in cerebral ischemia
(MERCI) device, filling of both divisions of the MCA and partial filling of the M1 segment are seen. Lower right panel: After a second pass of the
MERCI device, recanalization of all segments is seen.

neurologic status is ascertained regularly during the case c­ irculation. A microcatheter is then advanced over a
in order to determine potential response to treatment microguidewire to the level of occlusion. The microwire
in real time. and microcatheter are gently advanced through the occlu-
IA access is almost always via the femoral artery. If sion, along the expected trajectory of the parent vessel,
mechanical thrombolysis is contemplated, an 8F or 9F taking care to minimize trauma that might result from
sheath is placed; otherwise, a 5F sheath is adequate. A this essentially blind navigation. When the ­microcatheter
guide catheter is advanced into the symptomatic artery, is believed to be beyond the occlusion, a microcatheter
and detailed angiographic examination of the vascular angiographic run is performed, delineating the distal
anatomy, including the circle of Willis and leptomen- extent of the occlusion. In cases where tPA can be safely
ingeal collateral circulation, is performed. For carotid administered, small aliquots (e.g., 2 mg) typically are
cases, the common carotid artery is injected first in order injected slowly into the thrombus, as the microcatheter
to examine the cervical bifurcation. Continuous heparin is gradually withdrawn until it lies just proximal to the
flush is administered via the guide catheter. occlusion. At some centers, infusion pumps are used
An angiographic run via the guide catheter delineates for IA tPA administration. Control angiography via the
the proximal border of the intraluminal occlusion, and guide catheter is performed, and the process is repeated
delayed images delineate the extent of the collateral until the vessel is seen to have recanalized.
284 Section II  Procedures

Problem Solving: When Are Aggressive were compared, adjusting for differences in baseline
Mechanical Clot Disruption Techniques NIHSS score and age. Mortality rates did not differ sig-
Indicated? nificantly between embolectomy patients and PROACT
Aggressive mechanical clot disruption provides an II control patients (adjusted analysis: MERCI 29.1%,
advantage over IA pharmacolysis in potentially increas- Multi MERCI 18.0%, PROACT II control 27.1%).
ing the recanalization rate and speed and reducing the Given the differences in study design and baseline
total thrombolytic dose. Patients with contraindica- characteristics of patients, randomized clinical trials are
tions to tPA are candidates only for mechanical throm- necessary and currently under investigation (MR RES-
bectomy. Mechanical techniques are attempted after CUE trial [NIH protocol no. 04-N-0264], IMS III). In the
IA thrombolysis in patients who had no significant MR RESCUE trial, MRI will be used to compare embo-
response or persisting occlusion after repeated admin- lectomy using the Merci Retriever with standard treat-
istration of r-tPA and control angiography. Aggressive ment in acute stroke patients and to identify people who
mechanical clot disruption is defined as utilization of might benefit from the device. The primary objective of
at least one of the following interventional techniques: the NIH-funded, phase III, randomized, multicenter,
nn Aggressive microcatheter/microwire clot maceration open-label clinical IMS trial is to determine whether
nn Percutaneous transluminal angioplasty a combined IV/IA approach to recanalization is supe-
nn Stent deployment rior to standard IV r-tPA alone when initiated within 3
nn Use of a clot extraction device such as the MERCI hours of acute ischemic stroke onset. Subjects will be
retrieval system or the Penumbra system randomized in a 2:1 ratio with more subjects enrolled
Limited data are available about the use of angio- in the combined IV/IA group. If an appropriate throm-
plasty and stenting in the emergency treatment of intra- bus is identified, treatment will continue with either the
cranial lesions in patients with acute ischemic stroke. Concentric MERCI thrombus removal device, infusion
Percutaneous transluminal angioplasty consists of bal- of r-tPA, and delivery of low-intensity ultrasound at the
loon angioplasty in patients with persisting occlusion site of the occlusion via the EKOS Micro-Infusion Cath-
in the internal carotid artery and proximal MCA. Bal- eter, or infusion of r-tPA via a standard microcatheter.
loons are always undersized relative to the estimated The randomized, multicenter, clinical trial CLOTBUST
lumen diameter of the treated segment. An aggres- (Combined Lysis of Thrombus in Brain Ischemia using
sive combined endovascular approach of intracranial Transcranial Ultrasound and Systemic tPA) had shown a
thrombolysis and cervical carotid stent placement dur- 49% rate of complete recanalization or dramatic clinical
ing the acute phase has been advocated in patients with recovery from stroke within 2 hours after tPA bolus when
acute stroke who had severe ipsilateral cervical internal tPA infusion was continuously monitored with transcra-
carotid artery stenosis to timely reestablish intracranial nial Doppler compared with 30% among patients who
perfusion, effectively prevent early recurrent strokes, received tPA without ultrasound monitoring (P = .03).
and limit the incidence of reperfusion injury. Snare
devices are advanced through the microcatheter into the EXTRACRANIAL CAROTID
clot matrix with the intention of capturing the clot when ATHEROSCLEROTIC DISEASE
pulled. The MERCI device is a flexible, helical-shaped,
tapered tip made of nitinol wire. The MERCI comes in Background
three FDA-approved versions: the first generation of five
conical helical loops (X5, X6), the L-generation device Patients with carotid artery stenosis are at increased
consisting of cylindrical helical loops with arcading fila- risk for subsequent stroke, myocardial infarction,
ments to give greater grip to the clot (L5, L6), and the and death. The risk of stroke is greatest for persons
K-mini helical loops with countertwist to give more ten- with neurologic symptoms such as transient isch-
sile strength in smaller target lesions. First-generation emic attacks, but it also is increased in patients with
MERCI devices achieved recanalization rates of 48%, asymptomatic lesions. The proportion of all strokes
and, when coupled with IA thrombolytic drugs, recana- attributable to previously asymptomatic carotid steno-
lization rates of 60% have been reported. sis is small; however, in patients older than 60 years
Multi MERCI was an international, multicenter, pro- who have cerebral infarction, approximately 15% have
spective, single-arm trial of thrombectomy in patients ipsilateral carotid stenosis ≥70%. The frequency of
with large-vessel stroke treated within 8 hours of symp- hemodynamically significant carotid artery stenosis is
tom onset. The median NIHSS score was 19. Treatment higher in symptomatic patients than in asymptomatic
with the L5 Retriever resulted in successful recanalization patients. In 40% to 50% of patients with a complete
in 75 (57.3%) of 131 treatable vessels and in 91 (69.5%) stroke, the primary etiology of the stroke is related to
of 131 after adjunctive therapy (IA tPA, mechanical). extracranial carotid disease.
Overall, favorable clinical outcomes (modified Rankin Carotid endarterectomy (CEA) has been shown to
score [mRS] 0–2) occurred in 36%, and mortality was reduce the risk of stroke in patients with moderate-to-
34%. Both outcomes were significantly related to vas- severe carotid stenosis (>50% for symptomatic, >60%
cular recanalization. Symptomatic intracerebral hemor- for asymptomatic) in the North American Symptom-
rhage occurred in 16 (9.8%) patients. Josephson et al. atic Carotid Endarterectomy Trial (NASCET) and the
identified 68 patients in the MERCI and Multi MERCI Asymptomatic Carotid Atherosclerosis Study (ACAS).
trials who would have been eligible for PROACT II. Rates The benefits from surgery accrue only if the 30-day rate
of good outcome (mRS ≤2) and mortality at 90 days of perioperative stroke or death rate is 6% or lower for
 Chapter 6 Neurointerventional Radiology 285

patients with symptomatic and 3% or lower for those with severity of stenosis. The common and internal carotid

SECTION II
asymptomatic carotid stenosis. Technical or anatomic arterial diameters are measured, with special attention
risks related to the carotid lesion or medical comorbidi- paid to the landing zone for the protection device.
ties render surgery a higher risk for a subgroup of patients. After angiography, the lesion is crossed with the pro-
The perioperative risk of stroke or death has been tection device. A 3- to 4-mm balloon is advanced to the
reported to be elevated in patients with coexistent stenotic segment coaxially over the 0.014-inch wire hold-
symptomatic coronary artery disease, congestive heart ing the protection device, and angioplasty is performed.
failure, anatomic variations (high carotid bifurcation) The diameter of the stent is sized to the caliber of the larg-
and tandem lesions, ipsilateral intraluminal thrombus, est segment of the carotid artery in which the stent will be
contralateral carotid artery occlusion, postendarterec- deployed. After stent deployment, poststent dilation typi-
tomy restenosis, and radiation-induced carotid artery cally is performed using a balloon with a diameter match-
stenosis. These patients may be better served by carotid ing that of the internal carotid artery distal to the stent.
artery stenting, with a potentially lower risk with the Finally, the embolic protection device is removed, typi-
endovascular procedure. In 2004, the FDA approved cally using a dedicated retrieval catheter. At most centers,
the first carotid artery stenting system (Acculink stent the patient is awake during the entire procedure, enabling
and Accunet embolic protection device, Guidant, Santa continuous neurologic assessment. The patient typically
Clara, CA) for use in patients with ≥80% asymptomatic is monitored in an intensive care unit–like setting post-
carotid stenosis. procedure, with tight blood ­pressure control designed to
Cerebral embolization of friable atheromatous mate- lower the risk of postreperfusion hemorrhage.
rial from the aortic arch and the carotid artery has been
found to occur during all stages of the carotid artery What Are the Most Common Complications of
stenting procedure and may cause periprocedural neuro- Carotid Stenting, and How Are They Treated?
logic deficits. Several filters for distal embolic protection The various manipulations comprising carotid stenting
approved by the FDA include the Accunet, EmboShield may result in vessel dissection involving the common,
(Abbott Vascular, Redwood City, CA), the Spider (ev3), internal, or external carotid arteries. In order to mini-
and the EZ filter wire (Boston Scientific, Natick, MA). mize the risk of vessel perforation or dissection, in the
Devices to arrest or reverse anterograde internal carotid process of exchange maneuvers only large branches of
artery flow will soon be widely available. the external carotid artery should be used. In cases where
The Carotid Revascularization Endarterectomy versus symptomatic or flow-limiting dissection occurs, stent
Stenting Trial (CREST) is a randomized trial designed to deployment at the site usually is warranted. Antiplatelet
compare the efficacy of CEA with that of carotid artery regimens, initiated in preparation for the carotid stent-
angioplasty and stent placement with the aid of an ing procedure, are continued and followed by noninva-
embolic protection device in the prevention of stroke, sive imaging. In asymptomatic and non–flow-limiting
myocardial infarction, and death in symptomatic patients dissection, antiplatelet medication and clinical observa-
with >50% carotid artery stenosis and asymptomatic tion usually suffice.
patients with >70% stenosis. The Stenting and Angio- If the patient develops a sudden neurologic change
plasty with Protection in Patients at High Risk for End- during or after carotid stenting, either hemorrhage or
arterectomy (SAPPHIRE) trial compared carotid artery ischemia is likely. Rapid access to the target vessel should
stenting with CEA in high-risk patients with ≥50% symp- be obtained, and, in case of flow obstruction, emergent
tomatic stenosis and ≥80% asymptomatic stenosis. At 1 revascularization should be attempted. In case of neither
year, 12.2% of patients undergoing carotid artery stent- vessel cutoff nor slow flow on angiography, emergent
ing had suffered death, stroke, or myocardial infarction CT scan should be done to rule out hemorrhage. When
within 30 days and death or ipsilateral stroke between 31 hemorrhage is seen, heparin should be reversed with
days and 1 year compared to 20.1% of the CEA group. protamine and the blood pressure tightly controlled.
Rigorous medical treatment, timely intervention, inter- The major long-term complication of carotid stenting
ventionalists’ experience, and analysis of plaque com- is restenosis. The incidence of in-stent recurrent steno-
position may have important influences on the future sis varies tremendously depending on the duration of
treatment of patients with carotid artery stenosis. follow-up, the type of stent implanted, the implanta-
tion technique, and the imaging criteria used to define
How Is Carotid Stenting Performed? significant recurrent stenosis. Levy et al. found severe
Angioplasty and stenting can cause intimal injury that (≥80%) in-stent stenosis based on Doppler criteria in
promotes thrombosis, and stents themselves are highly 6 (5%) of 112 high-risk surgical patients. Six patients
thrombogenic when first deployed. Therefore, patients (three symptomatic) required repeated intervention.
are pretreated with a dual antiplatelet regimen (aspirin The rate of hemodynamically significant restenosis was
325 mg daily and clopidogrel 75 mg daily) for at least 3 comparable to published surgical restenosis rates.
days before stent placement. Anticoagulation is admin-
istered, targeting an ACT of 200-250 seconds throughout At What Intervals and How Should
the procedure. Head and neck CT angiography or MRA is the Patient Be Followed?
helpful in the planning phase to estimate the anatomic Duplex sonography evaluation is most commonly used
configuration of the large vessels and to select the devices for follow-up and typically is obtained before discharge,
most appropriate for their specific properties. Selective at 6 months, 1 year, and then annually thereafter. In the
carotid angiography is then performed to define the event of recurrent symptoms or evidence of hemody-
286 Section II  Procedures

namically significant stenosis on Doppler ultrasonogra- Two types of arterial aneurysms are associated with
phy, repeat angiography is performed. Restenosis may AVMs: (1) flow-related saccular aneurysms and (2) dys-
require repeated angioplasty, deployment of an addi- plastic aneurysms, most commonly within the nidus of
tional stent within the first, or a bypass procedure. The the AVM. Proximal flow-related aneurysms that appear
dual antiplatelet regimen of clopidogrel and aspirin is some distance from the lesion itself, on an arterial pedi-
maintained for 4 to 6 weeks postprocedure, after which cle supplying the AVM, have been reported to occasion-
patients typically remain on aspirin therapy alone. ally regress after occlusion of the AVM. These lesions are
more commonly seen in older age groups. In contrast,
CENTRAL NERVOUS SYSTEM most practitioners would recommend directly treating
dysplastic aneurysms early in the course of AVM treat-
ARTERIOVENOUS LESIONS
ment in order to lower the risk of bleeding (Figure 6-8).
There are many types of central nervous system (CNS) Dysplastic aneurysms have a female preponderance of
arteriovenous shunts, that is, lesions with direct transit up to 5:1, can be multiple, and are evenly distributed
of arterial blood into the venous system, with distinct through the second to sixth decades. Both types of AVM-
pathophysiology and treatment strategies. Cerebral AVMs associated arterial aneurysms are less commonly seen
are the most common, with a prevalence of approxi- during childhood.
mately 0.2% to 0.8%.
What Symptoms are Caused by Cerebral AVMs?
Brain AVM Intracranial AVMs may cause a number of symptoms,
including headaches, seizures, or progressive neurologic
How Are Brain AVMs Commonly Classified? deficit, but the most potentially devastating association
The widely used Spetzler and Martin classification incor- is intracranial hemorrhage, sometimes causing long-
porates the size of the AVM, the pattern of venous drain- term disability or death. Hemorrhage often occurs due
age, and the “eloquence” of the regions of the brain to rupture at a structurally weak point of the lesion, in an
involved by the AVM. This classification aims at defining arterial, intranidal, or venous location. Small AVMs and
the surgical risk of resection rather than the natural his- deep-seated lesions more frequently present with hemor-
tory profile of the AVM itself. rhage (86%) compared to large superficial AVMs (46%).

What Are Important Features of the How Are Intracranial AVMs Treated?
Angioarchitecture of AVMs? Management of intracranial AVMs is a multidisciplinary
Particular architectural features of the vasculature effort involving neurosurgeons, neurologists, and neu-
involved by the AVM are noted on angiography, as they rointerventionalists. The ultimate aim of treatment, not
may have an impact on the natural history of the lesion. always achievable, is complete cure through permanent
High-flow sequelae, such as kinking, plications, arte- occlusion of abnormal shunts. AVM can be treated by sur-
rial aneurysms, progressive arterial stenosis resulting gery, embolization, or radiosurgery, as well as through
in a moyamoya pattern, or the development of venous combinations of these modalities. Depending on the
stenosis or venous ectasias, can be associated with an local availability of treatment modalities and expertise,
aggressive clinical presentation. different institutions have developed individualized

Figure 6-8 Acute hemorrhage associated with basal ganglia arteriovenous malformation (AVM) as seen on noncontrast computed tomography
(left), CTA (middle), and catheter angiography (right) (left internal carotid artery injection). The hemorrhage occurred precisely at the point in the
AVM at which an aneurysm is seen on CTA and DSA (white arrows).
 Chapter 6 Neurointerventional Radiology 287

protocols. Generally ­speaking, surgical resection of the Which Embolic Agents are Used for AVM

SECTION II
nidus has been the primary mode of therapy in patients Embolization?
with small AVMs located in noneloquent areas, particu- Embolic agents fall into one of four types: liquid, par-
larly when the patient presents after bleed. Surgery also ticulate, balloons, and coils. By far, the most commonly
is useful for larger AVMs after the size of the malforma- used embolic agents are the liquid agents, which have
tion has been reduced by embolization. Radiosurgery been studied most extensively and provide the maxi-
is effective in smaller-sized AVMs, particularly those mum protection from AVM bleed/rebleed from vascular
located in surgically inaccessible areas. However, AVM malformations. At most centers, particulate agents, bal-
occlusion after radiosurgery occurs by a biologic cascade loons, and coils serve only adjunctive roles in the embo-
that typically requires 2 to 3 years to achieve its end- lization of brain AVMs.
point, and the patient may remain exposed to AVM risks The two most commonly used liquid embolic agents
during this time period. are Onyx and NBCA. Onyx (Micro Therapeutics, Inc.,
Endovascular treatment facilitates neurosurgical Irvine, CA) is an ethylene vinyl alcohol copolymer
intervention, potentially allowing safe resection of dissolved in the organic solvent dimethyl sulfoxide
­otherwise surgically treacherous lesions. Endovascular (DMSO). When the material comes into contact with
treatment also can be used in combination with radio- an aqueous solution such as blood, it precipitates over
surgery. A minority of AVMs can be treated by endovas- several minutes and forms a spongy cast. In order to pre-
cular techniques alone, particularly small AVMs and vent early precipitation, the microcatheter dead space is
those with simple angioarchitecture (Figure 6-9). AVMs slowly flushed with DMSO prior to injection of Onyx.
that have recently bled, with angiographically apparent Because of its slow precipitation, Onyx allows for pro-
weak points such as intranidal aneurysms or venous longed injections and aggressive embolization of a large
obstructions, typically are treated urgently by emboliza- target region from a single arterial pedicle. NBCA, an
tion, surgery, or both in combination. acrylic glue, is the other most commonly used liquid
embolic. It is a low-viscosity liquid that, on contact with
What Are the Techniques for Endovascular hydroxyl ions in blood, rapidly polymerizes to an adher-
Treatment of AVMs? ent solid. In order to prevent early polymerization, the
Endovascular treatment of cerebral AVMs requires gen- catheter is flushed with 5% dextrose prior to injection of
eral anesthesia with an arterial line for close monitoring NBCA. Unlike the more recently available Onyx, acrylic
of systemic blood pressure. A guide catheter is intro- glues have been used for several decades, with a conse-
duced into the parent artery supplying the AVM (typi- quent extensive set of teachings related to the develop-
cally an internal carotid or vertebral artery), through ment of technical proficiency with its delivery.
which a microcatheter can be advanced distally to the
site of the lesion. The guide catheters allow injection of What Are the Various Goals of Embolization
contrast to create a road map for intracranial navigation of Brain AVMs?
and to follow the progress of the procedure. The feeding Preoperative Embolization
arteries of the AVM are catheterized using appropriate Preoperative embolization facilitates surgical treatment
selections of microcatheters and microwires. The goal by reducing the flow in the arteriovenous shunt, decreas-
of superselective angiography is to achieve a position ing the size of the nidus, and reducing blood loss. High-
from which AVM is opacified by contrast and normal flow direct arteriovenous shunts, nidal regions supplied
brain arterial supply is not seen (Figure 6-9). Emboliza- by deep arterial feeders not in the pathway of surgical
tion can be performed using temporary or permanent approach, and areas of the AVM with associated aneu-
embolic material. rysms are the most important targets of embolization.

Figure 6-9 First panel: Frontal view of right internal carotid artery (ICA) injection in a patient with a focal arteriovenous malformation (AVM)
with a compact nidus and a small number of feeding pedicles. Second panel: Microcatheter injection from an intranidal position, ideal for embo-
lization. Only the AVM nidus and the draining vein opacify. Third panel: Frontal unsubtracted view showing the Onyx cast. Fourth panel: Frontal
subtracted view, postembolization, showing nonopacification of the AVM.
288 Section II  Procedures

Pre-Radiosurgery the ­cause-and-effect relationship between dural sinus

Embolization can reduce the size of the AVM nidus, mak- thrombosis and DAVF appears well established, other
ing the lesion more amenable to radiosurgery, although mechanisms likely are involved, as most cases of dural
there has been recent debate regarding the efficacy of thrombosis do not result in development of a dural
this approach. Nidal areas that contain aneurysms are ­fistula.
embolized in targeted fashion to offer added protection
from hemorrhage during the several-year latency period How Are DAVFs Classified?
after radiosurgery before the AVM is cured. Djindjian et al. defined four types of DAVF: type 1 drain-
ing via the ipsilateral sinus, type 2 draining toward the
Curative Embolization contralateral sinus, type 3 draining via cortical veins, and
A minority of AVMs have been reported to be cured by type 4 with venous ectasia. This classification system was
embolization alone, with a very wide range of reported designed to stratify the severity of the presenting symp-
percentages. AVMs most amenable to cure by emboliza- toms and the risk of intraparenchymal hemorrhage. A
tion are small lesions with few feeding arteries and a more commonly used classification system has been
compact nidus. proposed by Cognard et al.
nn I. Venous drainage into dural venous sinus with
Targeted Embolization anterograde flow within the sinus
In patients with AVMs that cannot be definitively treated, nn IIa. Venous drainage into dural venous sinus with ret-
targeted embolization of particular regions within the rograde flow within the sinus
AVM nidus may help in providing symptomatic relief nn IIb. Venous drainage into dural venous sinus with
as well added protection from bleeding. However, some anterograde flow within the sinus and cortical venous
evidence suggests that partial embolization of brain reflux (Figure 6-10)
AVMs may increase the risk of hemorrhage, so this nn III. Venous drainage directly into cortical veins (corti-
option is offered only in very particular circumstances. cal venous reflux only) with no shunting into a sinus

Staged Embolization How Do DAVFs Clinically Present?

Staged embolization usually is undertaken in large mal- The symptomatology of DAVFs is highly variable,
formations that are not surgically resectable or ame- depending on the location of the shunt, the type of
nable to radiosurgery in which repetitive hemorrhage venous drainage, and the flow characteristics. Presen-
has occurred. By staging occlusion of a large AVM, some tation may include exophthalmos, bruit, cranial nerve
believe that the hemodynamic consequences of rapid deficits, focal and global neurologic deficits, increased
elimination of a large shunt may be prevented. intracranial pressure, papilledema, and hydrocephalus.
The most devastating clinical presentation is intracra-
Dural Arteriovenous Fistulae nial hemorrhage.

Dural arteriovenous fistulae (DAVFs) are arteriove- Problem Solving: What Are the Therapeutic
nous shunts that are located within the walls of a dural Options for DAVF?
sinus or involve adjacent cortical veins. Proposed etio- The therapeutic strategy depends on the clinical presen-
logic factors are middle ear and intracranial infections, tation and angiographic evaluation. Patients with visual
trauma, surgery, and dural sinus thrombosis. Although loss, hemorrhage, and infarction and those with cortical

Figure 6-10 Left: Lateral view of right external carotid artery (ECA) injection showing opacification of a focally ectatic segment of the superior
sagittal sinus during the arterial phase of the injection, diagnostic of a dural arteriovenous fistula. There is reflux into the deep venous system from
the sinus (white arrow), imparting a risk of intracranial hemorrhage. Middle: Unsubtracted view of the Onyx cast at the fistulous points. Right:
Postembolization right ECA injection demonstrating nonopacification of the fistula.
 Chapter 6 Neurointerventional Radiology 289

venous drainage require prompt therapy. Djindjian type vascular malformations remains catheter-based angiog-

SECTION II
I fistulae on the other end, can be followed conserva- raphy.
tively without treatment.
Patients with DAVFs located in the posterior sigmoid What Is the Normal Blood Supply to the Spinal
or transverse sinus without severe symptoms or high- Cord?
risk angiographic features are potential candidates for The blood supply to the spinal cord is via one anterior
treatment by manual compression of the cervical carotid spinal artery (ASA) and two or more posterior spinal
artery, although the reported efficacy of this technique is arteries. The ASA lies in the anterior median sulcus, and
quite variable. the posterior spinal arteries lie on either side of the dor-
Superselective embolization via the external carotid solateral surface of the spinal cord. The ASA supplies
branch feeder to a DAVF can be an effective treatment the anterior two thirds of the spinal cord, including the
(Figure 6-10). A variety of agents are available to embo- anterior and lateral corticospinal tracts; the posterior
lize DAVFs, including polyvinyl alcohol (PVA) particles, spinal arteries primarily supply the posterior third of
liquid adhesive agents such as NBCA, and Onyx. Coils the cord.
can be used in adjunctive fashion to slow the flow for
subsequent injection of permanent liquid embolic Anterior Spinal Artery
agent. Proximal occlusion of a feeding artery should be The distal vertebral arteries, typically distal to the origin
avoided because future IA access and thus subsequent of the posterior inferior cerebellar arteries, are the typi-
treatment usually are precluded, while the fistula typi- cal origin of the ASA. Supply can arise symmetrically
cally recruits arterial supply from a neighboring collat- from both sides or predominantly from one side. From
eral vessel. the cervicomedullary junction to the conus, a single
Transvenous embolization typically involves deploy- ASA runs within the anterior median sulcus. In the cer-
ment of coils via a transvenous route under direct vical region, the ASA receives further contributions via
fluoroscopic guidance to achieve closure of DAVFs by branches of the vertebral artery as well as the ascend-
obstructing outflow. The transvenous route for emboli- ing cervical branch of the thyrocervical trunk (Figure
zation is tenable only if the sinus is not being used for 6-11). An important contribution to the ASA axis is a
venous drainage of normal brain. In some cases when prominent unilateral radicular artery, typically at the
the transvenous approach is not technically achievable C5 or C6 level, known as the artery of cervical enlarge-
by endovascular means, direct puncture of the sinus can ment (Figure 6-11). In the thoracic and lumbar regions,
be performed, followed by occlusion packing with coils. radiculomedullary branches of the supreme intercostal
Because most of the symptoms in DAVF can be related artery and the thoracic/lumbar segmental arteries join
to venous hypertension, recanalization of an occluded the ASA axis, exhibiting a characteristic hairpin turn as
or stenosed dural venous sinus using angioplasty or they descend to join the ASA axis in the midline. The
stenting may ameliorate symptoms by reestablishing most prominent of these radicular vessels is the artery
low-pressure anterograde venous drainage. of Adamkiewicz, which commonly arises from the
The combination of preoperative arterial and subse- lower intercostal or lumbar arteries, most frequently on
quent surgical excision of DAVF has been shown to be the left side, between T9 and L2. The artery of Adam-
effective in treating complex lesions. Particulate embolic kiewicz should always be identified angiographically
materials, although nonpermanent, can be used for pre- before performing thoracic or lumbar embolization
operative embolizations 24 to 48 hours prior to surgical or surgical procedures involving the lower thoracic or
excision. Finally, radiosurgery is increasingly being rec- upper abdominal aorta.
ognized as an effective modality for treatment of some
DAVFs.

SPINAL VASCULAR MALFORMATIONS

Introduction
Vascular malformations of the spine are uncommon
lesions that represent potentially treatable causes of
myelopathy. Their prevalence, expressed as a percentage
of the total number of spinal space-occupying lesions,
is reported at 16%. The ratio of spinal to brain AVMs
ranges from 1:4 to 1:8. The diagnosis and management
of vascular malformations of the spine and spinal cord
have undergone significant development since they were
first recognized as a clinical entity in 1888. Due to the
rarity of these lesions, variable clinical and radiologic Figure 6-11 Anterior spinal artery (ASA) axis in the cervical region.
presentation, bias of treating centers toward surgery or The ASA runs craniocaudad in the midline. The characteristic hairpin
turns of the radiculomedullary feeders are shown by the white and
endovascular therapy, and absence of uniform outcome black arrows. Left: Direct injection of a radiculomedullary feeder to the
parameters, a clear set of clinical guidelines has not yet ASA. Right: Left vertebral artery injection demonstrating the artery of
evolved. The gold standard in the diagnosis of spinal cervical enlargement (black arrow).
290 Section II  Procedures

Posterior Spinal Artery nn Intradural extramedullary AV fistulae (Figure 6-12).

The posterior spinal arteries originate as lateral spinal These are supplied directly by anterior or posterior
branches of either the vertebral arteries or the pos- spinal artery branches and typically have a simple
terior inferior cerebellar arteries. They also receive arteriovenous fistula morphology, rather than a nidus,
­contributions from the segmental radicular arteries with the fistulous point at a perimedullary location
at multiple levels. Although often presented as paired (on the surface of the cord, draining directly into the
structures, the posterior spinal arteries can be concep- perimedullary veins). They can present with progres-
tualized as two parallel paramedian craniocaudal net- sive myelopathy from venous hypertension, myelopa-
works of vessels on the posterior aspect of the spinal thy due to mass effect from massively dilated veins, or
cord. The ASA forms a basket-like anastomosis with the spinal hemorrhage.
posterior spinal arteries over the surface of the conus nn Intramedullary (or “glomus”)-type AVMs of the cord.
medullaris. These lesions are supplied by branches of the ante-
rior and/or posterior spinal arteries. They possess an
How Do We Classify Spinal Arteriovenous intramedullary nidus, which drains into the coro-
Lesions? nal venous plexus on the cord surface and then via
Various classification systems have been proposed and medullary veins or extradural veins in an anterograde
have been the subject of fierce debate. Rather than advo- manner. Patients typically are younger than 50 years.
cate for one system in particular, it is perhaps most use- There is no predilection for any part of the cord, and
ful to consider the precise location of the arteriovenous up to half of all patients present with subarachnoid
communication. Thus, spinal arteriovenous lesions may hemorrhage. Treatment, both surgical and endovas-
be classified as follows: cular, is particularly challenging.
nn DAVFs. These are the most common of the spinal nn Metameric or “juvenile”-type AVMs with intramedul-
arteriovenous lesions. The nidus typically is located lary, extramedullary, and often extraspinal components.
within or on the dura of the proximal nerve root The nidus in these cases often is quite diffuse. Treat-
sleeve in the neural foramen, typically at the point ment is very challenging and often is aimed at pal-
where the nerve root sleeve becomes intradural. liation.
Flow is from the nidus of the fistula retrograde into nn Epidural arteriovenous fistulae. These are extremely rare
the perimedullary veins on the cord surface (coro- lesions in which venous drainage occurs is via the
nal venous plexus). These lesions are thought to be epidural venous plexus (Figure 6-13). They have been
acquired, resulting from trauma or venous thrombo- reported to progress to involve perimedullary venous
sis. They are most common in men (with a 5:1 M:F drainage and thus potentially give rise to myelopathy,
predominance) between the ages of 50 and 70 years with a presentation similar to DAVF.
and typically present with progressive myelopathy.
Regardless of the actual fistula site, symptoms usually Problem Solving: Which Spinal Cord
are attributable to venous hypertension affecting the Arteriovenous Shunts Should be Treated?
most dependent segment of the cord, the conus. MRI All patients with symptomatic lesions should be con-
typically shows conus signal abnormality as the first sidered for treatment because symptoms typically
parenchymal manifestation. are manifestations of hemorrhage, spinal venous

Figure 6-12 Intradural, extramedullary spinal arteriovenous (AV) fistula. The patient presented with severe headaches and motor tics. First
panel: Sagittal T2-weighted magnetic resonance image demonstrating markedly enlarged intradural flow voids posterior to the spinal cord. Fron-
tal view of a right vertebral artery injection in early arterial (second panel) and late arterial (third panel) phases demonstrate a posterior spinal
AV fistula, with early opacification of massively enlarged perimedullary veins and reflux of arterialized venous blood up the cord to the posterior
fossa. Fourth panel: Unsubtracted frontal view demonstrating coil masses deposited at the sites of arterial inflow into the venous pouch. Fifth
panel: Postembolization injection of the right vertebral artery demonstrating nonopacification of the fistula. The anterior spinal artery axis is
nicely demonstrated (white arrow).
 Chapter 6 Neurointerventional Radiology 291

­ ypertension, or mass effect, which all are processes

h

SECTION II
TUMOR EMBOLIZATION
that pose a high risk of profound neurologic impair-
ment. Incidentally discovered spinal arteriovenous Preoperative embolization of vascular tumors of the
lesions that show imaging evidence of risk, such as head, neck, and CNS has become an important adjunct
arterialization of perimedullary spinal veins, should to the surgical treatment of these tumors. Hypervascu-
be treated ­prophylactically. If complete obliteration is lar tumors for which embolization may be indicated
not feasible, treatment of morphologically high-risk include hemangioblastomas, intracranial metasta-
portions of the lesion, such as associated aneurysms, ses, meningiomas, hemangiopericytomas, neurogenic
is undertaken. tumors (e.g., schwannomas), paragangliomas, juvenile
The potential risk posed by high thoracic or cervical nasopharyngeal angiofibromas, hemangiomas, esthe-
lesions is greater than that posed by more caudal lesions sioneuroblastomas, benign bone tumors, malignant
because upper extremity function and respiratory func- bone tumors, and extracranial metastases. The indica-
tion may be affected. For patients with lower thoracic or tions for embolization include the following:
lumbar AVMs who have a fixed deficit and in whom no nn Control surgically inaccessible arterial feeders
clinical improvement is likely, spinal hemorrhage may nn Decrease surgical morbidity by reducing blood loss
not be life threatening, and the indications for aggres- nn Shorten operative procedure time
sive treatment may be less compelling. In some patients nn Increase the chances of complete surgical resection
with severe pain and spasm, even noncurative emboli- nn Decrease the risk of damage to adjacent normal tissue
zation may help palliate symptoms. nn Relieve intractable pain

Figure 6-13 Spinal epidural fistula. Frontal (upper left) and lateral (upper right) views of a right vertebral artery injection demonstrate immedi-
ate opacification of the epidural venous plexus. The patient had presented with a new continuous heart murmur. Postembolization views, frontal
(bottom left) and lateral (bottom right), demonstrate runoff into the vertebral artery, with no opacification of the fistula.
292 Section II  Procedures

nn Decrease expected tumor recurrence a feeding pedicle and then PVA particles are injected in
nn Allow better visualization of the surgical field with a pulsatile fashion under fluoroscopic guidance. The
decreased overall surgical complication particles wedge in the arterioles and accumulate within
Palliative embolization of head, neck, and CNS the tumor bed, inciting necrosis. Some practitioners fin-
tumors may be indicated as the sole treatment for ish the embolization with coil ligation of the proximal
patients who present poor surgical risks, patients with feeder to prevent rapid rerouting and revascularization.
intractable hemorrhage, or patients with increasing neu- Recanalization after PVA particle embolization occurs
rologic deficits from tumor mass effect. over weeks and months as the periparticle thrombus
Ideally, an embolic agent is chosen that will devas- resorbs and the particles are phagocytosed.
cularize the tumor but spare the adjacent normal tissue. For permanent embolization, NBCA or Onyx, which
Liquid embolic agents, such as ethanol, acrylic agents, forms an occlusive cast in the feeding artery intratumor-
and Onyx, and the smallest-diameter particulate materi- ally, is used.
als can penetrate into the arteriolar tumor supply, but
care is needed in their use because their ability to pene- PEDIATRIC VASCULAR LESIONS
trate distally also poses a risk of damage to adjacent nor-
mal tissues. Relatively coarser particulate agents, such as Pediatric vascular lesions of the CNS comprise a het-
large-diameter PVA and Gelfoam, do not penetrate into erogeneous group of abnormalities such as aneurysms,
the tumor as deeply, but they are less likely to damage arteriovenous lesions, and occlusive diseases. Although
adjacent normal tissues. Embolic agents, such as liquids superficially similar to their corresponding adult lesions,
and coils, may be permanent or temporary, as is the case pediatric vascular lesions have crucial differences with
for the particulate agents. regard to clinical manifestations, angioarchitecture, and
management strategies. Moreover, limitations related
How Is Tumor Embolization Carried Out? to vascular access, contrast dose, and acceptable radia-
MRI is the mainstay of preprocedural noninvasive imag- tion dose all play a role in shaping neurointerventional
ing and typically demonstrates avid enhancement in treatment strategy in children. The presentation of CNS
hypervascular tumors following gadolinium adminis- vascular lesions in childhood is truly rare, so rigorous
tration. The extent of the tumor is evaluated, including natural history data are almost uniformly lacking.
encasement of the internal carotid or vertebral arteries,
dural enhancement, and invasion of other vital adja- Vein of Galen Malformations
cent structures. In the majority of cases, even if small
branches of the internal carotid artery are parasitized to Vein of Galen malformations (VGAMs) are rare intra-
supply the tumor, preoperative embolization is ­confined cranial vascular anomalies that constitute only 1% of
to the dominant external carotid artery supply in order all intracranial vascular malformations but 30% of
to achieve the most favorable risk-to-benefit ratio. ­vascular malformations presenting in childhood. The
In juvenile angiofibromas, the arterial supply arises lesion is characterized by shunting of arterial flow,
from the pterygopalatine portion of the internal max- typically from anterior and posterior choroidal arter-
illary artery. Recruitment of the accessory meningeal, ies, into an enlarged persistent embryonic vein dorsal
ascending pharyngeal, and ascending palatine arteries to the tectum, the median prosencephalic vein (the
is often seen with larger tumors. In paragangliomas, precursor of the true vein of Galen). VGAMs typically
the major supply comes form the ascending pharyngeal are subclassified as either choroidal, with a complex
artery branches, the stylomastoid branch of the occipital AVM-like nidus, or mural, with direct arteriovenous
artery, and the temporal branch of the middle menin- fistulae in the wall of the median vein. In patients
geal artery. The middle meningeal artery, which supplies with VGAM, venous drainage of the brain is rerouted
the dura of the sphenoid wing, cerebral convexities, and via alternative routes, and the median vein does not
much of the anterior cerebral fossa, is the most domi- participate in normal cerebral venous outflow; it is a
nant feeding vessel of meningiomas, although meningi- relatively insulated vascular route. Thus, unlike brain
omas often recruit adjacent meningeal arteries or invade AVMs in which the venous drainage pathway of the
the dura and recruit pial vessels. brain is exposed to high arterial pressures by virtue
It is crucial to search diligently for external carotid– of the lesion, the risk of hemorrhage from VGAM is
internal carotid anastomoses and anatomic variants, extremely low. With the advent of endovascular neu-
particularly those involving the middle meningeal rointerventional techniques, the prospects for success-
artery and ophthalmic artery, because these may pro- ful treatment of these lesions, once dismal, have now
foundly impact the ability to safely perform tumor much improved.
embolization. Superselective injections are necessary to
delineate cranial nerve supply or potentially hazardous How Do VGAMs Present, and What Is the
anastomoses with the internal carotid artery or vertebral Treatment Strategy?
artery. The clinical presentation of VGAMs covers a wide spec-
Preoperative embolization is most commonly per- trum, ranging from neonatal heart failure to headaches
formed using particles of PVA from 150 to 350 μm in in adulthood. Very-high-flow shunts typically present
diameter (Contour PVA particles, Boston Scientific, at birth with right-sided and left-sided heart failure,
Fremont, CA) suspended in a mixture of contrast and which if untreated rapidly leads to multiorgan failure
heparinized saline. The microcatheter is advanced into and death. Embolization within the first few days of life
 Chapter 6 Neurointerventional Radiology 293

is performed, targeting the highest-flow components typically is deferred until 5 or 6 months of age, when the

SECTION II
of the lesion. When embolization is effective, almost risks of intervention are lower but neurodevelopmen-
immediate improvement in the cardiopulmonary status tal setbacks have not yet occurred (Figure 6-14). For all
of the patient can be seen, and intraprocedural weaning interventions in the first year of life, the goal is not nec-
of pressors becomes feasible. However, intervention at essarily complete obliteration of the lesion but rather
this early age, given the technical challenges associated protection from the systemic and neurologic risks posed
with vascular access and the friability of the subependy- by untreated lesions.
mal veins, is fraught with risk. VGAMs occasionally are detected on prenatal ultra-
Lower-flow lesions may present with macroceph- sound scans (from approximately 25 weeks’ gestation
aly or mild heart failure at several months of age. Left and later) as a midline vascular mass. When VGAMs
untreated, these lower-flow lesions may lead to pro- are identified, prenatal MRI can be very helpful in
found impairment of neurologic development or even demonstrating the location of fistulae, presence of a
“melting brain syndrome,” with diffuse parenchymal nidus, the location of arterial feeders, ventricular size,
cerebral loss typically accompanied by calcifications. For and cerebral parenchymal changes. When diffuse brain
patients who have a stable cardiac status, a normal neu- parenchymal volume loss is present on imaging or in
rologic examination, and no macrocephaly, ­treatment the setting of multiorgan failure, the prospect of any

Figure 6-14 Vein of Galen malformation (VAGM), mural type. The lesion was found on routine third-trimester ultrasound. The patient was
clinically stable, and embolization was deferred until 5 months of age. Top left: Fetal magnetic resonance image demonstrating an enlarged
midline vascular structure, corresponding to the median vein of the prosencephalon, and diagnostic of a VGAM. Top right: Frontal view of a left
vertebral artery injection demonstrating early opacification of the ectatic venous pouch. Bottom left: Unsubtracted frontal view demonstrating
focal deposit of embolic material (detachable coils followed by Onyx) at the site of arterial inflow into the fistula. Bottom right: Postembolization
frontal view of a left vertebral artery injection demonstrating normal vertebrobasilar runoff, with nonopacification of the arteriovenous shunt.
294 Section II  Procedures

intervention leading to good neurologic and systemic Problem Solving: What Are the Treatment
outcome is nil. Options for Brain AVMs in Children?
Most practitioners prefer transarterial embolization Management strategies include single or combined ther-
as the treatment of choice. Although transvenous and apy including neurosurgery, transarterial embolization
transtorcular embolization have been advocated by with liquid agents such as NBCA or Onyx, radiosurgery,
some, it may be associated with higher morbidity and or a combination of techniques. However, the ability
usually is reserved for cases where transarterial emboli- to safely deliver radiation therapy in young children is
zation has failed. limited. Wherever possible, surgical resection of brain
AVMs in children is a desired endpoint, particularly
Pediatric Brain AVMs for lesions that have undergone hemorrhage. Although
growing attention is being paid to the possibility of
How Do Cerebral AVMs in Children Differ treating brain AVMs in adults with definitive emboliza-
from Those in Adults? tion alone, it should be borne in mind that AVMs are
In most surgical series, children represent 20% of all evolving lesions, and, particularly in children, residual
cerebral AVM cases. Arteriovenous fistulae are more often and dormant segments of the AVM may come to expres-
encountered in neonates; lesions detected in infants are sion at a later date. Periodic clinical and radiologic fol-
more often nidus-type AVMs. Cerebral AVMs frequently low-ups are warranted.
have characteristics in children that differentiate them
from their adult counterparts, such as multifocality (Fig-
Dural Sinus Malformations
ure 6-15), induced arteriovenous shunts remote from
the original lesion, large venous ectasia, venous throm- Lasjaunias and colleagues coined the term dural sinus
bosis, adjacent brain atrophy, and, particularly in neo- malformation to describe congenital dural fistulae that
nates and young infants, systemic phenomena such as occur early enough to preclude normal development
cardiac failure. Conversely, other features, such as flow- of the venous sinuses, resulting in giant dural lakes,
related arterial aneurysms, are relatively rare in children. typically involving the torcular, transverse, or supe-
In infants and young children, the clinical expression rior sagittal sinuses (Figure 6-16). Symptoms often are
of cerebral AVM is in many cases related to the remote ­systemic, with cardiac failure, coagulation disorders,
effects of the AV shunt on hemodynamic and hydro- or increased intracranial pressure leading to irritabil-
dynamic equilibrium, with signs of congestive heart ity, macrocrania, neurocognitive delay, and seizures.
failure, hydrocephalus, and seizures. After the age of 3 As opposed to VGAM where the venous sac drain-
years, more than 50% of AVMs present with intracranial ing the malformation does not participate in venous
hemorrhage. The next most common presentation is drainage of the brain, in dural sinus malformations the
seizure, which occurs in approximately 20% to 25% of cerebral venous system is intrinsically involved. Thus,
cases. Other presentations include headaches in 15% of the prognosis depends on the availability of alterna-
patients and focal neurologic deficit in fewer than 5% tive drainage pathways for cerebral venous blood, most
of cases. commonly achieved by ­“capture” of the cavernous
sinuses and rerouting of cerebral venous drainage ret-
rograde via the superior ophthalmic veins and emis-
sary veins to the facial and scalp veins. In cases with
favorable alternative pathways of venous drainage,
early embolization of arteriovenous shunts may allow
for normal development.

Figure 6-16 Frontal views of a left middle meningeal artery injec-

tion in early arterial (left) and late arterial (right) phases. A direct
fistula is seen, with a hole in the massively dilated torcular, through
which contrast enters with a “spigot” effect from the middle menin-
Figure 6-15 Multifocality of brain arteriovenous malformation geal artery (white arrow). The dysplastic morphology of the torcular
(AVM) in an infant. Note two discrete foci with AVM nidus (white and its incorporation of the medial aspect of the right transverse sinus
arrows) without a bridge seen angiographically. are apparent on the delayed image.
 Chapter 6 Neurointerventional Radiology 295

SECTION II
Figure 6-17 Moyamoya disease seen on frontal (top left) and sagittal (top right) views of left internal carotid artery (ICA) injection. Note stenotic
changes involving the terminal ICA and M1 segment as well as severe pruning of the middle cerebral artery (MCA) arterial tree. Postsynangiosis
views of left superficial temporal (bottom left) and middle meningeal artery (bottom right) injection. Note opacification of parts of the MCA can-
delabra on both of these latter injections.

kidney disease, fibromuscular dysplasia, Osler-Weber-

Pediatric Aneurysms
Rendu syndrome, coarctation of the aorta, moyamoya
Intracranial aneurysms in children represent <5% of syndrome, Marfan syndrome, Ehlers-Danlos syndrome,
the total number in the general population. Saccular or bacterial endocarditis, fungal infections, neurofibroma-
“berry” aneurysms constitute 50% to 70% of all cases, tosis type 1, and tuberous sclerosis all have been associ-
are multiple in 2%, and are most commonly located at ated with an increased incidence of cerebral aneurysms
arterial bifurcations of the circle of Willis, as they are in children.
in adults. Infectious or mycotic aneurysms are situ-
ated peripherally and comprise 5% to 15% of pediatric How Do Aneurysms Clinically Present
­aneurysms. Traumatic aneurysms account for approxi- in the Pediatric Population?
mately 5% to 15% of pediatric aneurysms, of which Cerebral aneurysms present with subarachnoid hemor-
40% involve the distal anterior cerebral artery, 35% rhage approximately 70% of the time in children; mass
involve vessels along the skull base, and 25% are cortical effect (20%), seizure, and stroke are other clinical pre-
in location. A combination of intraluminal, mural, and sentations. In the neonatal period and infancy, males
extravascular factors is responsible for the development are affected more commonly than are females. Although
of aneurysms, given a clear association with various radiographically, vasospasm after subarachnoid hemor-
disease processes that weaken the arterial wall. Condi- rhage seems to be more prevalent and severe initially,
tions such as autosomal dominant inherited polycystic children seem to be less susceptible to delayed ischemic
296 Section II  Procedures

deficits. As in adults, cerebral aneurysms in children can Brown Jr RD, Wiebers DO, Torner JC, O’Fallon WM. Frequency of intracranial
hemorrhage as a presenting symptom and subtype analysis: A population-
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Carballo RE, Towne JB, Seabrook GR, Freischlag JA, Cambria RA. An outcome
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Merland JJ, Riche MC, Chiras J. Intraspinal extramedullary arteriovenous intracranial thrombolysis and carotid stenting in the hyperacute
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Monsein LH, Jeffery PJ, van Heerden BB, et al. Assessing adequacy of collateral AJNR Am J Neuroradiol. 2007;28:1162-1166.
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99mTc-HMPAO SPECT. AJNR Am J Neuroradiol. 1991;12:1045-1051. self-expanding nitinol stent (Enterprise) for the treatment of wide-necked
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treatment of wide-neck intracranial aneurysms. Long-term angiographic and aneurysms. Neuroradiology. 2007;49:555-561.
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 chapter 7

Spine Procedures: Biopsies

Wade Wong and Danielle Nanigian

CONSIDERING TODAY’S WHAT CONSIDERATIONS SHOULD

WONDERFUL IMAGING, WHY WOULD BE MADE PRIOR TO BIOPSY?
ANYONE NEED A BIOPSY?
Preoperative biopsy considerations include a review
In spite of today’s excellent imaging modalities, imag- history and physical examination, imaging, laboratory
ing diagnoses are still a matter of presenting a reason- values (particularly coagulation profiles), and patient’s
able differential diagnosis and then making a best guess medications and allergies. Informed consent should be
based on clinical history, examination, imaging appear- obtained, and anesthetic requirements (for which the
ance, and other clinical features. No imaging allows patient may need to be NPO [nothing by mouth] prior
visualization of the cellular histology; therefore, tissue to the procedure) should be discussed.
sampling is necessary (Figures 7-1 and 7-2). Imaging review is necessary in deciding what needs to
One of the advantages of image-guided biopsies over be targeted and, if there are multiple targets, the order of
open procedures is that image-guided procedures are priority in which they should be taken. Based on loca-
performed percutaneously with minimal invasiveness, tion and risk of biopsy, the method of image guidance is
allowing the patient to have rapid recovery with rela- chosen. If the patient is in renal failure, iodine contrast
tively low risk. may be contraindicated, and this can be a disadvantage
Reasons for biopsy include establishment of a patho- when attempting to stay clear of vascular structures.
logic diagnosis when neoplasm is suspected, which is Laboratory findings of prime concern include coagu-
generally necessary prior to treatment. Biopsies can lation profiles. Generally an international normalized
be helpful in differentiating neoplasm from infection ratio greater than 1.5 is a reason to delay or defer biopsy.
because the two processes sometimes appear indistin- Elevated blood urea nitrogen and creatinine levels may
guishable. When infection is suspected and the patient indicate abnormal renal function that may preclude
is undergoing treatment but is not improving, a biopsy administration of iodine contrast.
can be helpful in establishing the appropriate antibiotic Patient medications may alter the timing of biopsy.
(sensitivity) for treatment. Typically patients who take warfarin (Coumadin) will

A B
Figure 7-1 A: A 56-year-old woman complained of backache and had a low-grade fever of 99.6°F. Her white blood cell count was 9,900.
­Magnetic resonance imaging reveals paravertebral fluid-filled rim-enhancing mass consistent with abscess. B: Computed tomography–guided
needle biopsy reveals malignant cells leading to eventual diagnosis of adenocarcinoma metastatic from stomach. This is an excellent example of
why tissue sampling is necessary for confirming diagnosis.

299
300 Section II  Procedures

stop the drug temporarily 5 days prior to the biopsy. anatomy relative to osseous landmarks. For those
Some patients require a temporary prescription for who are not adequately familiar with this anatomy,
enoxaparin (Lovenox) in place of Coumadin until 12 CT would be safer because adjacent soft tissues can
hours prior to the biopsy. Other medication consid- be readily identified and kept out of harm’s way. CT
erations include stopping clopidogrel (Plavix) 7 days is an excellent choice when soft tissue masses distant
prior and ticlopidine (Ticlid) 14 days prior to biopsy, to osseous landmarks must be biopsied. CT is also
particularly if the target is very close to the spinal canal advantageous when precise targeting is needed (e.g.,
in order to minimize the risk of epidural hematoma. adjacent to critical organs, such as the lungs, aorta, or
Aspirin and other nonsteroidal antiinflammatory drugs kidney).
usually are not a problem. For spine biopsies by the posterior oblique approaches,
Informed consent should consist of an explanation discography needle entry techniques are used. Both disc
of the reason for biopsy, other alternatives, a description and bone specimens can be safely retrieved. The proce-
of the procedure, including a discussion of appropri- dure usually is performed with the patient in the prone
ate anesthesia (usually local and conscience sedation), position. The fluoroscope is rotated about 45 degrees to
and an explanation of the risks, which include bleed- the side through which entry will occur. The superior
ing, infection, allergy, vascular injury, headache, nerve articular facet of the inferior vertebra is placed in the
injury, paralysis, stroke, and even death. In our experi- center of the obliquely visualized disc so that the needle
ence, complication rates are much less than 2%. is directed en face directly to the center of the target disc.
(The operator can use a set of forceps to thrust the needle
Spine Biopsies Lumbar: Problem swiftly to the target.) The superior margin of the inferior
vertebral body is flattened into a straight line appear-
Solving, How To Do It?
ance. This helps to project the exiting nerve root from
Challenges when performing biopsies of the lumbar the level above superior to the entering needle to avoid
spine include avoiding the kidney, bowel, aorta, inferior injury. Anteroposterior and lateral fluoroscopic views are
vena cava, and segmental arteries as well as injury to taken to confirm that the needle is correctly situated in
nerve roots and intraspinal contents. the center of the target. To obtain a sample, move the
Image-guided approaches for lumbar biopsies mainly needle in and out about 1 cm with rotation and aspira-
include the posterior oblique approach and the transpe- tion. The same technique can be used to approach osse-
dicular approach. ous lesions of the lumbar spine (Figure 7-3).
Fluoroscopy or computed tomography (CT) are the For L1–2 and L2–3, the image intensifier may need
common modalities for used for guidance. Operators to be rotated not only obliquely but also caudally. For
experienced with fluoroscopy find that fluoroscopic L5–S1, the image intensifier should be rotated cranially
guidance is more efficient and faster than CT, but it to allow the needle to clear the iliac crest. The opera-
requires a familiarity with adjacent unseen soft ­tissue tor should visualize a triangle consisting of the bottom

A B
Figure 7-2 A: A 36-year-old man positive for human immunodeficiency virus and PPD (purified protein derivative) complained of back pain
and lower-extremity weakness. The presumed diagnosis was tuberculous epidural phlegmon. B: Computed tomography–guided needle biopsy
reveals Candida instead of tuberculosis, which dramatically alters the treatment. This is an example of how imaging without image-guided tissue
sampling is relatively nonspecific.
 Chapter 7 Spine Procedures: Biopsies 301

of the L5 vertebral body, the medial border of the iliac to adjacent critical structures such as the kidney, aorta, iliac

SECTION II
crest, and the lateral border of the superior ­articular arteries, or inferior vena cava; Figures 7-9 and 7-10).
facet. The needle must pass through this triangle.
A curve on the needle may help the needle to pass up Thoracic Spine Biopsies: Problem
and over the iliac crest. Upon reaching the level of the Solving, How Dangerous? How To
L5–S1 disc, a twist on the needle will allow it to pass
Perform?
into the disc parallel to the end plates. In cases of very
high iliac crests, the triangle may be very difficult to visu- Challenges to performing thoracic spine biopsies include
alize. Side bending the patient away from direction of avoiding the lung, aorta, inferior vena cava, heart, nerve
the needle entry may help to open this space (Figure roots, and spinal cord. Other challenges are complica-
7-4). In some situations, entry into the L5–Sl disc may tions related to extreme kyphotic curvatures, diminished
not be feasible. An alternative method would be trans- visualization because of large shoulders, and difficult
pedicular approach through the L5 pedicle. If the disc entries because of small pedicles. In addition, the tho-
needs to be sampled in addition to the bone, the trajec- racic pedicles are angled more superiorly to inferiorly
tory of the needle can be angled superiorly or inferiorly than are lumbar pedicles, which are oriented more hori-
to reach the suspicious disc. zontally. This makes it necessary to carefully scrutinize
Transpedicular biopsies use the same technique as the angle of entry, particularly of upper thoracic pedicles
vertebroplasty and kyphoplasty. The transpedicular on the lateral fluoroscopic view in order to avoid pierc-
entry is an extremely safe means of obtaining tissue ing the exiting nerve root and to set the proper starting
samples when done properly. However, you should be point on the skin (usually more superior that expected).
careful to avoid a path that enters too medially so as CT is frequently used for thoracic spine biopsies. CT
not to breach the spinal canal (lateral recess) or enters permits clear visualization of adjacent structures that
too inferiorly so as not to injure the exiting nerve in the need to be avoided (Figure 7-11).
neuroforamen (Figures 7-5 through 7-8). The typical entries for thoracic biopsies include the cos-
For facet joints biopsies, a posterior oblique approach tovertebral approach and the transpedicular approach.
is taken with the needle directed en face into the slit In the costovertebral approach, the needle passes just
of the joint. For sacroiliac joint aspirations, a medial to lateral to the pedicle and medial to the adjacent rib head
lateral approach usually is taken when performed by (Figure 7-12). This allows the needle pass from poste-
fluoroscopy. Remember that the synovial portion of the rior to anterior with a lateral to medial angulation for
sacroiliac joint is the more inferior portion, whereas the more centralized sampling. When this approach is taken
fibrous portion is the more superior portion. by fluoroscopy, the operator must concentrate on visual-
CT is advantageous over fluoroscopy when the targets are izing the pedicle (to stay away from the spinal cord) and
difficult to visualize fluoroscopically or when biopsies must the rib head (to keep the needle medial to the rib head
be done with very precise targeting (often to avoid injury so as to avoid injury to the lung) (Figures 7-13 and 7-14).

A B
Figure 7-3 A: A 43-year-old male with a history of intravenous drug abuse complained of low back pain and had an elevated temperature to
101.3°F. B: Prone oblique approach.
continued
302 Section II  Procedures

C D

E
Figure 7-3, cont’d C: En face view of the forceps guiding the needle to the target in typical discographic technique. The superior articular facet
bisects the diameter of the disc. The needle is started just anterior to the superior articular facet. This helps to target the needle on the center of the
disc. D: Lateral orthogonal confirmatory view. E: Anteroposterior orthogonal view confirms that the needle is centrally located.
 Chapter 7 Spine Procedures: Biopsies 303

SECTION II
A B

D E
Figure 7-4 A: For L5–S1 disc biopsy, discographic technique is used. In order to visualize the open triangle between the S1 superior articular
facet, the iliac crest, and the inferior end plate of L5, the fluoroscope must be turned not only obliquely but also cranially (tip of forceps points
to open triangle). B: An aid to L5–S1 disc entry is applying a bend on the end of the needle, which allows it to rise over the iliac crest and then
level out in the plane of the disc with a final twist of the wrist. C: Another aid to clearing the iliac crest is side bending the patient away from the
direction of entry. D: Anteroposterior view of L5S1 discogram demonstrating L5–S1 disc entry technique with curved needle rotated to parallel
the disc margins. E: Lateral view of L5–S1 discogram with curve of the needle finally rotated to parallel the axis of the disc after it had been passed
over the iliac crest and downward to the L5–S1 disc.
304 Section II  Procedures

C C
Figure 7-5 A: A 58-year-old man complained of low back pain and Figure 7-6 A: A 57-year-old woman complained of back pain and
had a low-grade fever. He was unable to complete the magnetic reso- had hematuria. This cases demonstrates a potential problem with the
nance imaging examination, so postcontrast scans were not available. posterolateral approach in that the renal mass might be inadvertently
He had six lumbar vertebra and very high iliac crests, which made punctured because it cannot be seen fluoroscopically. B: An alterna-
biopsy at L6–S1 difficult. B: A transpedicular approach was selected. tive to the posterolateral approach is the transpedicular approach
The needle is directed through the L6 pedicle. C: From the transpe- performed fluoroscopically. C: Lateral view. Pathologic diagnosis con-
dicular approach the needle is angled upward to include the L5–6 disc. firmed renal cell carcinoma metastasis. Making this diagnosis led to a
Pathologic diagnosis is Escherichia coli infection. less invasive treatment option.
 Chapter 7 Spine Procedures: Biopsies 305

SECTION II
Figure 7-7 Safe technique for transpedicular biopsy involves
engaging the pedicle by staying away from the medial border
(spinal canal) and inferior border (neuroforamen).

Cervical Spine Biopsies: Problem Anteroposterior approaches can be performed tran-

Solving, Isn’t This Risky? How To sorally. Challenges include airway integrity, sterility,
and oral access maintenance. For the airway, the patient
Perform?
should be intubated with a sealing cuff to prevent fluids
Challenges to performing cervical spine biopsies include (e.g., secretions, blood, sterilizing fluids) from entering
avoiding the carotid and vertebral arteries, jugular vein, the airway prior to the procedure. Preparation can be
nerve roots, cranial nerves, spinal cord, esophagus, and done with povidone–iodine (Betadine). We typically
trachea. use a plastic vaginal speculum to keep the mouth open.
A variety of approaches for cervical spine biopsies CT guidance is required because the targeting must be
can be used, all of which carry elevated risk compared very precise to avoid penetrating too deeply and injuring
to thoracic and lumbar approaches. The approaches the spinal cord (Figure 7-19).
include posterior oblique (through the pedicle), ante- For anterolateral approaches, fluoroscopy can be
rior lateral (similar to cervical discography), or direct used similarly to cervical discographic technique.
anterior to posterior (transoral). Because the esophagus is situated slightly to the left
Because of the critical targeting, CT guidance is most of the midline, the typical approach starts from the
frequently relied upon for cervical spine biopsies. right. The technique consists of pressing firmly along
For posterior lateral approaches, a smaller needle the anteromedial aspect of the sternocleidomastoid
may be needed because the pedicles are very small. Be muscle in such a way to displace the carotid sheath
aware of the course of the vertebral artery as it enters laterally and the visceral space (trachea and esopha-
the transverse foramen at C6 and exits at C1 to pass gus) medially. This permits a small window of oppor-
into the foramen magnum. The carotid sheath includes tunity in which to start the needle toward the center
the carotid artery, the jugular vein, cervical sympathet- of the spine. In the process of starting the needle,
ics, cranial nerves IX through XII, and internal jugu- the fluoroscope can be activated momentarily. Once
lar lymph nodes. The facial nerve and external carotid the needle has entered superficially past the carotid
artery run through the parotid gland and usually are sheath and visceral space, a set of forceps can be used
located posterior to the mandible. The cervical nerve to direct the needle either into the targeting disc space
roots exit the neuroforamen and take an anterolat- or onto the vertebral body. Because the cervical spine
eral–inferior course. Because of the complex nature of components are small, multiple orthogonal planes
­adjacent ­vascular structures that are frequently difficult should be frequently scrutinized in order to avoid
to visualize even by CT, iodine contrast may be neces- injury to vertebral artery, nerve roots, and spinal cord
sary (Figures 7-15 through 7-18). (Figure 7-20).
306 Section II  Procedures

A B

C D
Figure 7-8 A: A 66-year-old male complained of low back pain. Plain films reveal destruction of posterior elements of L1 and L2. B: Axial T1
at L2 level showing mass invading posterior elements. C: T2-weighted images demonstrating expansile masses of the posterior elements of L1
and L2. D: Even though this biopsy would be more clearly guided by computed tomography or magnetic resonance imaging, it still can be safely
performed under fluoroscopic guidance by keeping the needle in the midline and staying posterior to the spinal laminar line. Pathologic diagnosis
is adenocarcinoma metastatic.
 Chapter 7 Spine Procedures: Biopsies 307

SECTION II
B

E
Figure 7-9 A: A 48-year-old woman with a history of breast cancer presented with suspicious lesion. B: Identifying reference grids on skin sur-
face. C: Using the laser light at the cut level referable to the lesion, distances can be measured from the reference marks on the skin to the expected
starting point, after which angle of trajectory and depth of needle can be established. D: Setting local anesthetic needle along intended course.
E: Parallel (tandem) technique of guiding the biopsy needle along the course of the already satisfactorily set anesthetic needle to the target point is
used in this case. Coaxial passage is another option but requires initial placement of a needle larger than the biopsy needle. Pathologic diagnosis
is intraosseous disc (not metastasis).
308 Section II  Procedures

Figure 7-10 A 47-year-old man complained of right lower back

pain. The enlarged clinically painful psoas muscle would be difficult to
identify on fluoroscopy but can be easily identified and targeted under
computed tomographic (CT) guidance. Thus, one of the important con-
siderations favoring CT over fluoroscopy is a soft tissue target without
bony landmarks. Biopsy was performed with a 25-gauge thin needle,
which retrieved adequate cells to diagnose a transitional cell carcinoma
before the primary was found.

A B

C D
Figure 7-11 A: A 65-year-old man complained of weight loss and upper back pain. Computed tomography (CT) of the thorax reveals lytic
lesion of T8. B: CT guidance for biopsy is often preferred when precise targeting is needed, such as adjacent to lung or critical blood vessels (e.g.,
aorta). C: For thoracic spine biopsies, a costovertebral approach permits safe needle passage medial to the rib head and along the lateral base of
the pedicle. Staying medial to the rib head, whether by CT or fluoroscopy, helps to keep the needle out of the lung. D: Pathologic diagnosis is
squamous cell carcinoma metastasis.
 Chapter 7 Spine Procedures: Biopsies 309

SECTION II
Figure 7-12 Example of computed tomography–guided costoverte-
bral approach. Pathologic diagnosis is prostate cancer. Figure 7-13 Fluoroscopically guided needle biopsy at T5 level
using the costovertebral approach. Note how the needle tip is lateral
to the pedicle and medial to the rib head. The forceps controls the
needle deliberately, preventing the weight of the needle handle from
toppling the needle and possibly causing injury to the lung.

A B
Figure 7-14 A: A 40-year-old paraplegic man in urosepsis. Magnetic resonance imaging reveals worrisome appearance of discitis and osteomy-
elitis at T12–L1. B: Fluoroscopically guided large-core biopsy was performed at the level of the disc parallel to a costovertebral trajectory. Patho-
logic diagnosis was fibrosis, aseptic consistent with neuropathic changes.
310 Section II  Procedures

A B

C D
Figure 7-15 A: Odontoid view showing lytic defect at C2 level in a 77-year-old woman who complained of increasing neck pain. She had a
history of breast cancer 15 years prior and mycobacterium 5 years prior. She was told that she was cured of both. B: Axial T1 postgadolinium dem-
onstrates enhancing mass center of the vertebral body of C2. The trajectory for biopsy of this lesion is precarious with the vertebral artery, carotid
sheath, pharynx, spinal cord, and nerve roots surrounding the target. C: Axial T1 postgadolinium at the level of the neuroforamen demonstrating
a more accessible target on the pedicle–lamina junction. D: The most accessible and safest approach is often the best. Pathologic diagnosis is
breast cancer metastasis.
 Chapter 7 Spine Procedures: Biopsies 311

SECTION II
A B
Figure 7-16 A: A 42-year-old man complained of upper neck pain. B: Biopsy trajectory taken to avoid possible injury to vertebral artery exiting
nerve root and spinal cord should needle overshoot the target. Pathologic diagnosis is aneurysmal bone cyst.

A B

C
Figure 7-17 A: An 84-year-old man complained of upper neck pain. Computed tomographic (CT) scan reveals enlargement and altered min-
eralization of the right lateral facet of C1. B: Obtaining access to this lesion risks causing injury to the vertebral artery, facial nerve, carotid sheath,
exiting nerve root, and spinal cord. C: The needle is precisely directed through a tight space. Pathologic diagnosis is prostate carcinoma metastasis.
This example demonstrates the value of CT for precise targeting.
312 Section II  Procedures

A B

C D
Figure 7-18 A: A 77-year-old woman with a medical history of breast cancer and diabetes. B: Targeting challenges include the vertebral artery
and carotid sheath. Because the lesion could represent infection, a trajectory through the pharynx is avoided. C: A rigid 180-gauge needle is
directed posterior to the carotid sheath and then angled anteriorly. D: After shoving the carotid sheath anteriorly with the shaft of the needle, the
needle is redirected to sample the lesion. Pathologic diagnosis is Escherichia coli infection.
 Chapter 7 Spine Procedures: Biopsies 313

SECTION II
A B
Figure 7-19 A: A 54-year-old man positive for human immunodeficiency virus and with a history of lymphoma complained of neck pain.
His temperature was 99.9°F, and his white blood cell count was 9,900. Abnormal enhancement included odontoid, C1, and the clivus. Surgeons
were uncomfortable with performing biopsy. B: Percutaneous biopsy targeting is difficult from almost any angle. Challenges include the carotid
artery, facial nerve, mandible, pharynx, vertebral artery, nerve root, and spinal cord. A transoral approach was taken. Challenges, which include the
airway, sterility, and maintaining an open mouth, were resolved by tracheal intubation, use of Betadine preparation, and use of a plastic vaginal
speculum. Pathologic diagnosis is Enterobacter infection.

A B C
Figure 7-20 A: Anterolateral approaches for cervical spine biopsies can be performed under fluoroscopic guidance using cervical discographic
technique. Enter from right side of neck (because esophagus lies left of midline); press down between carotid sheath and visceral space (just ante-
rior to sternocleidomastoid muscle); and direct needle to target, checking on anteroposterior (AP) and lateral views for confirmation. B: AP view
confirming that needle is correctly positioned in center of target. C: Lateral view confirming that needle is correctly positioned in target (and not
elsewhere, e.g., in spinal cord).
314 Section II  Procedures

A B
Figure 7-21 A: A 27-year-old man complained of increasing weakness and spasticity. Differential diagnosis included syrinx versus neoplasm
such as astrocytoma. B: Intradural intramedullary needle biopsy was performed with 25-gauge needle and very gentle aspiration. Cerebrospinal
fluid (CSF) was acquired and confirmed the diagnosis of syrinx. Subsequently 11 ml of CSF was removed for syringe provocative drainage test. The
patient’s symptoms improved. This led to intraoperative syrinx drainage for long-lasting decompression.

INTRADURAL BIOPSIES: ISN’T as to avoid the spinal cord. The patient must remain
compliant and still during this procedure. In addition,
THIS FOR NEUROSURGEONS?
correct orientation without excessive rotation must be
Intradural biopsies may be simply a matter of collecting maintained. This may mean aligning the rami of the
cerebrospinal fluid (CSF) for diagnosis of meningitis. mandible as a reference so that consistent orientation is
However, if fluid is needed for diagnosis of ­intradural maintained. Orthogonal views should be obtained fre-
tumor (e.g., lymphoma or drop metastases), then a quently during the procedure.
large-volume sampling may be required in order to Intradural biopsies may also involve soft tissue masses
obtain a sufficient cells for diagnosis. intradurally. The introduction of myelographic contrast
A lumbar puncture is commonly performed under and/or the use of CT or even magnetic resonance imag-
fluoroscopic guidance. A straight down between the spi- ing (MRI) may be helpful in visualizing the target. Biopsy
nous processes approach usually works well on young of a lesion of the spinal cord is a high-risk procedure
patients. However, in older patients with degenerative that could lead to permanent neurologic injury, particu-
bony hypertrophy, a translaminar approach may be larly if bleeding occurs. If an intradural soft mass must
more reliable in gaining needle passage. A translaminar undergo image-guided biopsy, a thin 25-gauge needle
approach is taken from a slight lateral to medial angu- with very gentle movements and very conservative aspi-
lation with the needle directed to the sublaminar zone ration should be considered. In most cases, intradural
of the level above the entry site. Visualization under biopsies should be reserved for those with direct neuro-
­fluoroscopic guidance is usually accentuated by slight surgical expertise (Figures 7-21 and 7-22).
caudal angulation of the image intensifier.
WHAT TO BIOPSY WHEN THERE
Problem Solving: Canal Stenosis ARE MULTIPLE TARGETS?
and Lumbar Puncture
When multiple targets are present, target selection
Remember that the conus usually is situated about T12– should be considered in order of priority based on rela-
L1, and entry should be below that level. Older patients tive risk, accessibility, visualization, and operator confi-
often have limited flow of CSF below L4–5, not uncom- dence (competence) (Figures 7-15 and 7-23).
monly because of a higher degree of central canal steno-
sis at L4–5 and perhaps also at L3–4. Therefore, if CSF WHAT TO DO WHEN THE BIOPSY
fails to flow with a lumbar puncture at L5–S1, a second IS DONE?
attempt should be made perhaps at the L2–3 level.
If there is clinical evidence or suspicion of blockage Postbiopsy risks include bleeding, vasovagal responses,
to the flow of CSF, a C1–2 puncture, the needle should and anesthetic and sedation recovery. Therefore, patients
be placed in the posterior third of the spinal canals so should be watched either in a holding area or in a
 Chapter 7 Spine Procedures: Biopsies 315

SECTION II
A B C
Figure 7-22 T1 postgadolinium images in sagittal (A) and axial (B) views demonstrating densely enhancing mass surrounding the conus and
filling the subconus space in a 27-year-old woman who was progressively developing cauda equina syndrome. B: Axial image. C: Fine-needle
biopsy was gently performed intradurally with a 25-gauge needle. Pathologic diagnosis is chromic lymphocytic leukemia.

A B
Figure 7-23 A: A 47-year-old woman complained of low back pain. She had a low-grade fever of 100.8°F and a history of intravenous drug
abuse. Referring physicians requested a spine biopsy. An additional lesion was observed at the right acetabulum. Because the patient was hav-
ing difficulty laying still while she demanding more opiates, the more easily accessible and lower-risk target (the acetabular lesion) was chosen.
B: Biopsy of the acetabulum was performed in less than 5 minutes. Pathologic diagnosis is breast cancer metastasis. Targeting the more easily
accessible, lower-risk lesion first often is a better choice.
316 Section II  Procedures

­ ostanesthesia care unit for a reasonable period of time,

p necessary, particularly for delicate soft tissue abnormali-
possibly 1 to 2 hours, until established discharge criteria ties. Straight (e.g.. Chiba, Francine, Crown) needles in
are met. If a prebiopsy embolization for a hypervascular 25, 22, 20, and 18 gauges can be used for sampling cells
mass or an abscess drainage was performed, then a higher from soft tissue masses. Crown and Francine needles of
level of recovery care, such as inpatient admission or per- similar gauges have teeth at the tip that tend to shred and
haps even ICU admission, should be considered. How- cut tissue so that a small core of tissue can be obtained
ever, most needle biopsies are performed on an outpatient (Figure 7-24).
basis, so postbiopsy patient instructions more commonly Techniques for MRI-guided biopsies are similar
include answers to questions such as when it is safe for the to those for CT, but it is important to ensure that the
patient to eat, drive, bathe, and return to work. Follow-up patient has no contraindication to entering a magnetic
instructions should be given and appointments made. field and that the patient does not have any device or
product (e.g., ferromagnetic screws) that can cause pro-
WHAT ARE THE TOOLS OF THE found susceptibility artifact and thus obscure imaging
of the target. In addition, titanium rather than stainless
TRADE?
steel needles (of which the available variety is limited)
Depending on the nature of the biopsy, a variety of need to be used.
different types of biopsy needles can be used. In some For osseous lesions, bone biopsy needles from 17
situations, a thin 25-gauge needle may be all that is to 11 gauge and even larger may be chosen. For CT

A
B

C D
Figure 7-24 A: Straight needles are available in a variety of diameters and lengths. The needle used here was a 20-gauge, 6-inch Chiba needle,
which was moved in and out along the disc and angled superiorly and inferiorly to sample the subchondral end plates. Diagnosis is staphylococcal
discitis/osteomyelitis. B: This lytic lesion was easily sampled using a 20-gauge Crown needle, which has teeth at the tip and tends to yield a core rather
than simply cells. Pathologic diagnosis is adenocarcinoma. C: An 18-gauge Chiba needle was used to yield the diagnosis of breast cancer metastasis.
 Chapter 7 Spine Procedures: Biopsies 317

g­ uidance, the 17-gauge EZM or 15-gauge Ostycut nee- bone in young patients. In these situations, placement

SECTION II
dles, which do not have heavily weighted handles, may coaxially of the 17-gauge easy-M needle in the 11-gauge
be advantageous because they can be placed in soft tis- Jamshidi needle may help to loosen the bone core for
sues under CT guidance without falling out of trajectory retrieval. Alternatively, another consideration is use of
when released. For larger sampling of bone, 11-gauge a drill such as a 3-mm Kyphon drill through a cannula
Jamshidi type needles can be used (Figure 7-25). in order to obtain a bone core. When large amounts of
Bone cores may be difficult to retrieve when the bone material must be retrieved, the 9-gauge Kyphon biopsy
is extremely hard, such as osteoblastic bone or very dense device may be selected (Figures 7-26 and 7-27).

A B

C D
Figure 7-25 A: The 17-gauge EZM bone biopsy needle is available in different lengths (5, 7.5, 10, 12.5, 15 cm). It is ideal for computed tomog-
raphy–guided biopsies because it can be set in soft tissues along its intended trajectory and it does not have a heavy handle that would cause it
to fall off course. B: The tip of the EZM bone biopsy needle is sharp, constricted, and threaded so that it easily drills into hard bone and reliably
retrieves samples. C: EZM needles easily drilled into dense bone yield the diagnosis of non-Hodgkin lymphoma. D: The EZM bone biopsy needle
can be coaxially passed through a larger 11-gauge bone needle during vertebroplasty if a biopsy sample is needed.
318 Section II  Procedures

A B

C
Figure 7-26 A: For blastic bone lesions, the pathologist may require a substantial quantity for diagnosis. An 11-gauge needle may be needed
to provide a sufficient sample. However, retrieving a bone core may be difficult in cases with extremely dense bone. B: Washing bone out of the
grooves of the Kyphon drill. C: Numerous bone fragments from the Kyphon drill.

For difficult soft tissue biopsies in paraspinous soft A needle guide for coaxial passage may be neces-
tissue or for soft tissue masses invading bone, spring- sary (Figure 7-28). For fluid-filled abnormalities, a
loaded cutting-type needles (e.g., Temno) may be micropuncture set with placement of a guidewire and
selected for more reliable collection of core material. subsequent drainage catheter may be considered. For
However, these needles have a heavy handle and a cut- aspirating fluid, usually a large syringe will be chosen
ting extension that protrudes forward such that these over a small syringe because the amount of suction can
needles can be awkward and somewhat risky to use in be quite a bit greater. For drainage of an abscess pocket,
the spine. a cope-type looping catheter seated within the fluid
 A

B
Figure 7-27 A: To obtain very large samples needed by the pathologist for diagnosis, a 9-gauge Kyphon biopsy device can be passed through
an 8-gauge canula coaxially. B: The 9-gauge Kyphon biopsy device as it is passes through the 8-gauge canula.

A B

CUTTING
CANNULA

INNER
STYLET

C
Figure 7-28 A: A 67-year-old woman complained of upper neck pain. She had a medical history that included breast cancer, uterine cancer, and
lymphoma. Biopsy is needed because treatment is not the same for all three. B: Ten fine-needle passes fail to retrieve an adequate sample. C: The
spring-loaded cutting needle works well on soft tissue targets. Remember that the inner stylet projects a distance beyond the cutting canula. This
must be considered carefully when setting the depth from skin to target so as not to injure critical anatomy, especially in the neck. Also remember
that the handle has some weight that can cause the needle to deviate off course if not supported. Usually the safest technique consists of directing
the needle coaxially through an already established guiding needle. Pathologic diagnosis is uterine cancer (made on first pass).
320 Section II  Procedures

A B

D
C
Figure 7-29 A: A 36-year-old man 5 days post lumbar laminectomy complained of increased low back pain and fever. Determining the diag-
nosis was straightforward, but treatment could be effected percutaneously with image guidance. B: Cope drainage catheter was placed to drain a
large pus pocket. C: Cope drainage catheter was placed under ultrasound guidance. D: After the fluid was drained, the fever and back pain resolved
overnight. Pathologic diagnosis is Staphylococcus epidermidis infection.
 Chapter 7 Spine Procedures: Biopsies 321

pocket with drainage to suction (e.g., by Jackson-Pratt or, if antibiotics are present, delay the biopsy, if fea-

SECTION II
bulb) maybe be considered (Figure 7-29). sible, until the patient has been off the antibiotics for
1 week (Figure 7-30).
RESULTS: WHAT CAN BE To ensure that an adequate tissue sample is acquired,
the presence of a pathologist technician at the proce-
EXPECTED?
dure to receive samples is recommended. Ideally, the
Positive results: When infection was suspected sample is prepared and reviewed with the pathologist
N = 88 patients at the time of the procedure to determine if the sam-
71 positive (7 delayed up to 7 weeks because of ple is adequate and, in many situations, diagnostic. If
slow growth from underlying granulomatous this extra step is not taken at the time of the procedure,
disease) not infrequently the procedure needs to be repeated
80% positivity at a later time because samples are inadequate and/or
Positive results: When neoplasm was suspected ­nondiagnostic.
N = 92 patients Hypervascular neoplasms may pose a danger when
85 positive performing a biopsy because of potential ­uncontrollable
92% positivity hemorrhaging. If high vascularity (e.g., renal cell can-
Overall 86% positivity cer, thyroid metastases) is suspected, then preopera-
Complication Rate tive embolization may be prudent. This usually entails
2 small hematomas selective transarterial particle embolization, although in
1 needlestick to operator some situations coaxial biopsies with final injection of
1.6% rate Gelfoam down the outer guiding needle may suffice. If
osteoplasty is contemplated, then coaxial biopsy with
Problem Solving: What Are injection of polymethylmethacrylate will help to cause
hemostasis (Figure 7-31 and 7-32).
the Pitfalls?
Needle safety is extremely important for both the
Failure to diagnose is one of the more common pit- operator and the patient. Avoid leaving needles ­carelessly
falls. For neoplasm, this may be due to failure to on the patient or on the work table. Use caution when
sample the correct area of abnormality. This is more handling and passing needles so as not to cause needle-
likely to occur under fluoroscopic guidance than CT sticks. Avoid capping needles; a needle holder is worth-
guidance, in which case a repeat procedure under CT while to prevent inadvertent needlesticks. Dispose of
or even MR guidance may be worthwhile. For situa- needles properly. When pushing needles into a patient,
tions where infection is suspected, the presence of anti- have adequate control of the needle so as not to inadver-
biotics may hinder growth. Therefore, try to obtain a tently injure an organ that was not intended for penetra-
biopsy sample prior to the start of antibiotic therapy tion (Figure 7-33).

A B
Figure 7-30 A: A 57 year-old man complained of increased low back pain and low-grade fever 10 days post L5–S1 discectomy. He had been
started on antibiotics 3 days earlier. B: Biopsies performed at L4–5 and L5–S1 yielded scant Staphylococcus epidermidis that could be a contaminant.
An infectious disease consultation suggested discontinuing the antibiotics for 1 week. Repeat biopsy 1 week later revealed numerous colonies of
S. epidermidis. The lesson here is to try to biopsy before antibiotics are given or to discontinue the antibiotics for at least 1 week when biopsies
results are negative in the face of suspected spinal infection.
322 Section II  Procedures

A B

C
Figure 7-31 A: A 67-year-old man complained of low back pain. Computed tomographic (CT) scan reveals a large area of sacral lysis.
B: Magnetic resonance imaging reveals numerous serpentine flow voids suggesting considerable hypervascularity of the sacral mass. C: Angiogram
performed prior to biopsy confirms the hypervascular nature and the need to devascularize prior to biopsy.
 Chapter 7 Spine Procedures: Biopsies 323

SECTION II
D E

F
Figure 7-31, cont’d D: Superselective catheterization of feeder from the right internal iliac artery isolates the tumor blush. E: Embolization is
performed by flow-directing 200-μm polyvinyl alcohol (PVA) particles until tumor vascularity from this vascular supply ceased. F: Superselective
angiogram via microcatheter of feeder subbranch from left internal iliac artery demonstrating contralateral tumor blush prior to embolization
with 200-μm PVA particles.
Continued
324 Section II  Procedures

I
G

H
Figure 7-31, cont’d G: Postembolization angiogram of left internal iliac artery demonstrating devascularization of tumor mass from this
vascular territory. H: Biopsy is performed under CT guidance with 17-gauge EZM bone biopsy needle and 22-gauge Crown needle coaxially. Some
bleeding continued. I: Gelfoam is prepared to stop bleeding along needle tract. Gelfoam is first flattened. J: Gelfoam is cut into thin longitudinal
strips.
 Chapter 7 Spine Procedures: Biopsies 325

SECTION II
K L

M
Figure 7-31, cont’d K: Gelfoam is cut horizontally into small squares and dropped into a syringe. L: Gelfoam is mixed with iodine contrast
(Omnipaque 240) and injected back and forth through a three-way valve to form a slurry. The needle is replaced back along its original track, and
the Gelfoam slurry is injected along the track for hemostasis. M: Gelfoam can be seen post slurry embolization. Bleeding stopped shortly thereaf-
ter. Pathologic diagnosis is cordoma of sacrum and renal cell carcinoma of right kidney without metastasis.
326 Section II  Procedures

A B

C D
Figure 7-32 A: A 57-year-old man complained of middle back pain and weakness of the lower extremities.T2-weighted sagittal image reveals
lower thoracic epidural mass severely compressing the dural sac as well as a suspicious lower cervical mass. B: Magnified image of T10 demon-
strating a compression fracture with a retropulsing mass extending posteriorly as well as a flow void suspicious for increased vascularity. C: Spinal
angiogram demonstrating hypervascularity of the T10 mass. Embolization prior to biopsy would be prudent. D: Superselective microcatheteriza-
tion of left T10 intercostal. Coils are placed distally to protect the distal intercostal artery. Polyvinyl alcohol (PVA) particles (200 μm) are flow
directed into the tumor feeders until devascularization occurs.
 Chapter 7 Spine Procedures: Biopsies 327

SECTION II
E F
Figure 7-32, cont’d E: Post left T10 intercostal artery embolization image demonstrating absence of tumor vascularity on this side. The contra-
lateral side was subsequently embolized similarly. The biopsy proceeded without incident. Pathologic diagnosis is thyroid carcinoma metastasis
to T10. F: Identifying the artery of Adamkiewicz, which has a classic hairpin, is important because inadvertent embolization could cause spinal
cord infarction and subsequent paralysis.
328 Section II  Procedures

A B

C D

F
E
Figure 7-33 A: One the most hazardous aspects of performing spine biopsies is needle injury to the operator. This is hardly the scene conducive
to safe practice. Keep sharps neat and orderly to prevent accidents. B: Treat needles like firearms. Do not point them where they can cause injury. C:
When passing needles, hand them off with the nonsharp side first. D: Avoid capping needles. E: Keep needles in an orderly container. F: Dispose
of sharps responsibly so that nursing, technical, and janitorial personnel do not suffer injury.
 Chapter 7 Spine Procedures: Biopsies 329

Suggested Readings Raininko R, Sonninen P. Dorsal CSF space at CI-CII level: technique of cervical

SECTION II
myelography. Neuroradiology. 1987;29:73-75.
Babu NV, Titus VTK, Chittaranjan S, et al. Computed tomographically guided Rankine JJ, Barron DA, Robinson P, Millner PA, Dickson RA. Therapeutic
biopsy of the spine. Spine. 1994;21:2436-2442. impact of percutaneous spinal biopsy in spinal infection. Postgrad Med J.
Cameron DC. Percutaneous coaxial trephine bone biopsy. Austral Radiol. 2004;80:607-609.
2007;51:370-374. Robertson HJ, Smith RD. Cervical myelography: survey of modes of practice
Chen Y, Chang G, Chen W, Hsu H, Lee T. Local metastases along the tract and major complications. Radiology. 1990;174:79-83.
of the needle: A rare complication of vertebroplasty in treating spinal Rodriguez-Catarino M, Blimark C, Willen J, Mellqvist U, Rodjer S. Percutaneous
metastases. Spine. 2007;32:E615-E618. vertebroplasty at C2: case report of a patient with multiple myeloma and
Hadjipavlou AG, Kontakis GM, Gaitanis JN, Katonis PG, Lander P, Crow WN. a literature review. Eur Spine J. 2007;16:S242-S249.
Effectiveness and pitfalls of percutaneous transpedicle biopsy of the spine. Sachs DC, Inamasu J, Mendel EE, Guiot BH. Transoral vertebroplasty of renal
Clin Orthop Rel Res. 2003;411:54-60. cell metastasis involving the axis. Spine. 2006;31:E925-928.
Heyer CM, Al-Hadari A, Mueller K, Stachon A, Nicolas V. Effectiveness Schirmer CM, Malek AM, Kwan ES, Hoit DA, Weller SJ. Preoperative
of CT-guided percutaneous biopsies of the spine: An anaylsis of 202 embolization of hypervascular spinal metastases using percutaneous direct
examinations. Acad Radiol. 2008;15:901-911. injection of N-butyl cyanoacrylate: technical case report. Neurosurgery.
Huegli RW, Schaeren S, Jacob AL, Martin JB, Wetzel SG. Percutaneous cervical 2006;59:431-432.
vertebroplasty in a multi-functional image-guided therapy suite: Hybrid Tehranzadeh J, Tao C, Browning CA. Percutaneous needle biopsy of the spine.
lateral approach to C1 and C4 under CT and fluoroscopic guidance. Acta Radiol. 2007;8:860-868.
Cardiovasc Intervent Radiol. 2005;28:649-652. Uemura A, Matsusako M, Numaguchi Y, Oka M, Kobayashi N, Niinami C,
Jelinek JS, Kransdorf MJ, Gray R, et al. Percutaneous transpedicular biopsy of Kawasaki T, Suzuki K. Percutaneous sacroplasty for hemorrhagic metastases
vertebral body lesions. Spine. 1996;21:2035-2040. from hepatocellular carcinoma. AJNR Am J Neuroradiol. 2005;26:493-495.
Layton KF, Thielen KR, Wald JT. A modified vertebroplasty approach for spine van de Krats EB, van Walsum T, Verlaan J, Voormolen MH, Mali WPTHM,
biopsies. AJNR Am J Neuroradiol. 2006;27:596-597. Niessen WJ. Three-dimensional rotational x-ray navigation for needle
Layton KF, Thielen KR, Wald JT. Percutaneous sacroplasty using CT fluoroscopy. guidance in percutaneous vertebroplasty: an accuracy study. Spine.
AJNR Am J Neuroradiol. 2006;27:356-358. 2006;31:1359-1364.
Lis E, Bilsky MH, Pisinski L, Boland P, Healey JH, O’Malley B, Krol G. Wong W. personal experience 1996-97 oral presentation at ASNR “Common Spine
Percutaneous CT-guided biopsy of osseous lesion of the spine in Interventions: Percutaneous Biopsies” (Abstract). Philadelphia, Pennsylvania:
patients with known or suspected malignancy. AJNR Am J Neuroradiol. American Society of Neuroradiology 36th Annual Meeting; May 17-21,
2004;25:1583-1588. 1998.
Nourbakhsh A, Grady JJ, Garges KJ. Percutaneous spine biopsy: a meta-analysis. Wong W. Lumbar Spine Biopsy. PocketRadiologist: Interventional Top 100
J Boint Joint Surg Am. 2008;90:1722-1725. Procedures. Peter Rogers, Anne Roberts, Peter Schloesser, Wade Wong (eds).
Petsas T, Tsota T, Kalogeropoulou CP, Liatsikos EN. Application of a new W.B. Saunders Company, Salt Lake City, Utah, 2003, pps 250-252. Reprinted
guiding system in percutaneous biopsies. Cardiovasc Intervent Radiol. in: PDA Version: PocketRadiologist: Interventional 100 Procedures. W.B.
2007;30:276-280. Saunders Company, Salt Lake City, Utah, 2003, pp 250–252.
Pierot L, Boulin A. Percutaneous biopsy of the thoracic and lumbar spine: Wu L, Li C Chen L, Li C, Qiu X. Magnetic resonance imaging bone biopsies in
transpedicular approach under fluoroscopic guidance. AJNR Am J the iPath-200 system. Chin Med J. 2003;116(6):937-940.
Neuroradiol. 1999;20:23-25. Yaffe D, Greenberg G, Leitner J, Gipstein R, Shapiro M, Bachar G. CT-guided
Puri A, Shingade VU, Agarwal MG, Anchan C, Juvekar S, Desai S, Jambhekar percutaneous biopsy of thoracic and lumbar spine: a new coaxial technique.
NA. CT-guided percutaneous core needle biopsy in deep-seated AJNR Am J Neuroradiol. 2003;24:2111-2113.
musculoskeletal lesions: A prospective study of 128 cases. Skeletal Radiol.
2006;35:138-143.
 chapter 8

Neurodegenerative Disorders
Manzoor Ahmed and Michael Phillips

The term neurodegenerative disease generally refers to s­ yndrome characterized by slowness and depression.
evolving structural neuroanatomic changes with pro- Subcortical dementia is a sequela of processes primarily
gressive deterioration in the patient’s condition. Neu- affecting the thalamus, basal ganglia, and related brain-
rodegenerative disorders (NDDs) would be a relatively stem nuclei, with relative sparing of the cerebral cortical
simple subject if it comprised only Alzheimer disease functions. It typically is seen in PD, Huntington disease,
(AD) and Parkinson disease (PD). Although NDD and progressive supranuclear palsy (PSP).
clearly is a more complicated topic, AD and PD provide Presenile dementia: Also termed early-onset dementia.
a good basic framework for more complete discussion. Onset is before age 65 years. Commonly due to AD and
They are the predominant dementing and movement vascular dementia, followed by frontotemporal demen-
disorders, respectively, and serve as an excellent frame tia (FTD) and multiple acquired causes, some of which
of reference for consideration of other processes. may be reversible.
Brain NDDs are primarily a clinical diagnostic Senile dementia: Also termed late-onset dementia.
domain. Morphologic and functional imaging play Mostly due to AD and other less common NDDs.
a significant role in the diagnosis of NDDs. They (1) Movement disorders: A common but heterogenous
complement the clinical diagnosis, (2) act as a problem group of disorders. In the majority of patients, the clini-
solver in some difficult cases, (3) exclude treatable mim- cal diagnosis is not difficult (e.g., idiopathic Parkinson
ickers of a specific NDD, and (4) provide one means for disease [IPD] or essential tremor). PD is the second most
further research. common neurodegenerative disease after AD. Our focus
is on IPD and its mimickers, clinically termed atypical Par-
DEFINITIONS kinson disorders. The accuracy of clinical diagnosis of PD
and neurodegenerative mimickers is generally very good,
As with all fields of endeavor, it helps to know the vocab- but up to 10% to 20% of cases may still be misdiagnosed.
ulary. Following are some useful definitions to keep in Atypical Parkinson disorders: Several primary
mind when thinking about NDDs. NDDs have in common parkinsonian features such as
Dementia: Generally means loss of mental func- bradykinesia, rigidity, tremor, and gait disturbances.
tions, such as thinking, memory, and reasoning, which These neurologic conditions are associated with com-
is severe enough to interfere with a person’s daily func- plex clinical presentations that reflect degeneration in
tioning. Dementia is not a disease itself but rather a various neuronal systems resulting in the term Parkinson
group of symptoms that might accompany certain dis- plus. They include multisystem atrophy (MSA), progres-
eases or conditions. Diagnostic criteria is “impairment sive supra-nuclear palsy (PSP), corticobasal degenera-
in short and long term memory and at least one other tion (CBD), dementia with Lewy bodies (DLB), and PD
cognitive dysfunction or personality change, significant with amyotrophic lateral sclerosis (ALS). Vascular (usu-
social and occupational impairment and absence of ally due to striatal lacunar infarcts), drug-induced, and
organic factors causing the mental disorder” (Diagnostic viral encephalitis-related parkinsonisms are secondary
and Statistical Manual of Mental Disorders, Fourth Edi- causes of parkinsonism. Importantly, these processes
tion). Dementia is clinically divided into cortical and rarely respond to levodopa therapy, which often clini-
subcortical dementias. cally distinguishes them from IPD.
Cortical dementia: Primarily affects cognitive pro- Synucleinopathies: The term synucleinopathies is used
cesses such as memory, intellect, and language. AD and to name a group of NDDs characterized by fibrillary
Creutzfeldt-Jakob disease (CJD) are two definite forms aggregates of alpha-synuclein protein in the cytoplasm
of cortical dementia. Patients with cortical dementia of selected populations of neurons and glia. These disor-
typically show aphasia, agnosia, and apraxia in addition ders include PD, DLB, pure autonomic failure, and MSA.
to severe amnesia. However, the clinical differentiation Tauopathies: A class of NDDs resulting from the
of cortical from subcortical dementia may be difficult in pathologic aggregation of tau protein, a neuronal micro-
some cases. tubule stabilizing protein, resulting in a neurofibrillary
Subcortical dementia: Subcortical dementia con- tangles. In normal brain, tau protein is soluble and
trasts neuropsychologically and anatomically with nonfilamentous. Tau protein is found in AD and fronto-
Alzheimer-type dementia. It occurs in degenerative temporal degeneration. Other tauopathies include PSP,
extrapyramidal disorders as well as in inflammatory, CBD, and FTD-parkinsonism linked to chromosome 17.
infectious, and vascular conditions. It is a clinical Argyrophilic grain disease, a late-onset dementia, is a

333
334 Section III  Problem Solving: Disease Categories

tauopathy. It is similar to PSP and CBD on an immu- increase. However, these are general rules that are often
nohistochemical analysis but is different clinically, with difficult to apply directly to individuals. Successful aging
mild limbic dementia features mimicking AD. is a term often applied to subjects who demonstrate rel-
atively preserved functions compared to the age cohort.
Problem Solving: Is There Normal Although the term has become relatively popular, clear
rigorous definitions are not available. Importantly, there
Aging? (Figure 8-1, A)
is significant overlap in the imaging appearance of nor-
Normal brain aging is a relative term with regard to phys- mal aging and NDDs, particularly in the early stages of
ical and functional abilities, with declining mental func- disease progression. We divide the magnetic resonance
tions but no severe compromise of cognitive and motor (MR) appearance of aging brain into three categories:
performance. In general, during normal aging, cognitive 1. Normal brain except for mild volume loss. No white
functioning declines as cortical gray matter and hip- matter hyperintensities. This may be the imaging
pocampus decrease and white matter hyperintensities marker of “successful aging.”

A B

C D
Figure 8-1 Aging. A: Axial computed tomography in an asymptomatic case with bilateral dense symmetric globus pallidi calcifications, sparing
the putamina. B: Axial fluid-attenuated inversion recovery (FLAIR) image showing an unremarkable brain of an 80-year-old man with “successful
aging.” C: Axial FLAIR image of a 78–year-old man with mild diffuse patchy white matter T2 hyperintensities. D: Axial T2 image of an octogenar-
ian showing prominent perivascular spaces.
 Chapter 8 Neurodegenerative Disorders 335

2. Mild to moderate diffuse cerebral volume loss, vary- Susceptibility-weighted imaging is more sensitive than

SECTION III
ing grades of periventricular, and patchy white matter conventional axial T2* imaging and should be routinely
T2 hyperintensities. The majority of elder individu- performed in patients older than 50 years. Multiple cav-
als fall into this category. ernous malformations (type IV) as multiple susceptibil-
3. Profound diffuse cerebral volume loss, and varying ity foci, typically found in younger patients, can be a
grades of periventricular and patchy white matter T2 diagnostic challenge in rare cases. Similarly, multiple
hyperintensities. small hemorrhagic metastases presenting as pure hem-
Volume loss “atrophy”: We prefer the term volume orrhagic small foci are also very unusual.
loss to atrophy, although the terms are used interchange- Enlarged Virchow-Robin spaces: Virchow-Robin
ably in this review. Imaging is only capable of deter- (VR) spaces increase in size and frequency with advancing
mining volume loss at the present level of technology. age. Dilated VR spaces typically occur in three character-
Atrophy is really a histopathologic term suggesting istic locations. Type I VR spaces appear along the lenticu-
loss of neurons and axons in glial cells. Although vol- lostriate arteries entering the basal ganglia through the
ume loss is often produced by atrophy, other potential anterior perforated substance (”subcapsular”). Type II VR
causes include hydration status and drug therapy (e.g., spaces are found along the paths of the perforating med-
steroids). Volume loss clearly correlates with advanc- ullary arteries as they enter the cortical gray matter over
ing age. Cerebral volume loss is diffuse and generally the high convexities and extend into the white matter
mild, with more prominent ventricular enlargement. (“subcortical and subinsular”). Type III VR spaces appear
Volumetric magnetic resonance imaging (MRI) analysis in the midbrain (“peduncular”). Enlarged VR spaces is a
is a potential tool for serial longitudinal imaging. Mild nonspecific finding; they are seen in all age groups and
diffuse cerebellar hemispheric and posterior vermian in multiple neurodegenerative disorders as well as some
volume loss is consistently present in older individuals. inflammatory and metabolic storage disorders.
The rate of volume loss can vary considerably among MR spectroscopy: MR spectroscopy demonstrates
individuals. mild progressive changes in association with normal
White matter T2 changes: Aging brain shows grossly aging. Allowing for interregion and intersubject vari-
two types of white matter changes: (1) white matter ability, there is generally decreased percent N-acetylas-
hyperintensities in the deep and subcortical white mat- partate (NAA) and its ratios, specifically in the mesial
ter, graded as punctuate (grade 1), patchy or beginning temporal lobes, semiovale, and cortices, representative
confluent (grade 2), and confluent (grade 3); and (2) of diminished neuronal density and dysfunction. In
periventricular hyperintensities surrounding the lat- contrast, percent choline and its ratios are increased in
eral ventricles. Periventricular hyperintensity is graded these regions, reflecting increased glial activity.
as caps surrounding the frontal or posterior horns and Diffusion tensor imaging: Aging results in a mild
pencil-thin lining along the lateral ventricles (grade 1), but significant increase in the apparent diffusion coef-
bands along the lateral ventricles (grade 2), and irreg- ficient (ADC), whereas fractional anisotropy is progres-
ular changes extending into deep white matter (grade sively reduced. These findings appear to accelerate after
3). These findings are very nonspecific; however, in the age 70 years. The declines in fractional anisotropy and
absence of other risk factors or known existing condi- the increase in diffusivity reflect a loss of myelin and
tions, they are suggestive of changes related to underly- axonal fibers and an increase in extracellular space.
ing vascular processes. T2 hyperintensities can also be
seen in the corpus callosum with increasing aging and Problem Solving: Is There a Clinical
correlates with periventricular and deep white matter
Diagnosis of NDD?
hyperintensities.
Basal ganglia iron deposition and calcifications: A common indication for brain imaging is memory loss.
The brain progressively accumulates iron in both the Memory loss is clinically nonspecific and often reflects
gray and white matter. The most prominent increases the subjective symptoms of the patient rather than the
in iron levels occur in the globus pallidus, dentate, results of formal testing demonstrating memory loss
substantia nigra (pars reticulata), and red nuclei. Iron in comparison to age-matched cohort. It is important
accumulates to a lesser extent in the caudate, putamen, to interpret the imaging study in light of the provided
thalamus, cerebral cortex, and white matter after age 30 clinical diagnosis. Morphologic imaging helps in deter-
years. Hypointensity of the putamen usually does not mining the specific diagnosis by complementing the
appear until the seventh decade. Iron deposition corre- clinical diagnosis but should not be used as a primary
lates to T2 hypointensity. T2*-based imaging (e.g., gra- initial tool for diagnosis. For example, MRI of the brain
dient-echo T2 and susceptibility-weighted imaging) is of a patient with no history of degenerative disorder
more sensitive to iron deposition. Bilateral basal ganglia interpreted as “unequivocal bilateral temporo-pari-
calcifications are a common finding related to aging. etal volume loss as suggestive of either mild cognitive
Physiologic calcification is generally limited to globus impairment or Alzheimer’s disease” is appropriate only
pallidi, and the calcification can be asymmetric or pres- in the setting of a strong clinical history. If the patient
ent on only one side. is given a specific diagnosis by a neurologist, the neu-
Multifocal microhemosiderin deposits: Manifests roimager’s job is fairly easy. It is the group of patients
as susceptibility foci. They are seen with increasing age suffering from disorders with overlapping clinical pre-
but are confounded by hypertension and nonspecific sentations who require supplementary imaging that will
small-vessel disease including amyloid angiopathy. assist the clinician with a diagnosis. The categories of
336 Section III  Problem Solving: Disease Categories

NDDs discussed below, reflects the common indications Progressive ataxia: Spinal (e.g., Friedreich ataxia,
for acquiring an imaging study, usually as “a problem- Machado-Joseph disease). Hereditary cerebellar ataxia
solving tool.” (e.g., autosomal dominant or recessive olivopontocer-
Dementia-dominant disorders: Mainly includes AD, ebellar atrophy). Acquired cerebellar ataxia (e.g., para-
vascular dementia, FTD, and dementia with Lewy bodies neoplastic, alcohol-related, idiopathic cerebellar ataxia
(DLB). Evaluate the sulcal prominence and associated [usually late onset]).
ventricular dilatation with focus on the selectivity and
diffuse feature of the atrophy. If available, voxel-based Problem Solving: Are Cerebral
morphometry or other volumetric measures can be used. Atrophy, Hypoperfusion, and
Note that the methods require careful correction for cal- Hypometabolism Selective or
varial size as well as age. Coronal plane can be used for
Nonselective?
subjective assessment of hippocampal atrophy. Tools are
available for quantitative measures of hippocampal vol- Generally, we estimate the selectivity of volume loss, for
umes. Specify small- and large-vessel ischemic changes example, bilateral dominant occipital lobe volume loss in
in vascular dementia. Use susceptibility-weighted imag- PCA or bifrontal volume loss in FTD. We will be correct
ing for detection of hemosiderin parenchymal depos- in most cases if we follow the basic rule (i.e., interpreta-
its, a stigmata of small-vessel ischemic disease and/or tion in light of clinical diagnosis). If available, volumetric
hypertension and cerebral amyloid angiopathy. Exclude analyses should be used. Note that the routine use of bio-
focal frontotemporal focal lesions, which may clinically metric analysis in the clinical setting is somewhat limited
mimic FTD. due to the relative lack of software approved by the United
Rapidly progressive dementia: Rapidly progressive States Food and Drug Administration. Until recently, soft-
dementias develop subacutely over weeks to months, ware solutions for biometric analysis were largely research
but sometimes over days. The most important role of tools. The approved packages now available may provide
neuroimaging is to identify signs of prion disease (i.e., useful information in the evaluation of volume loss. In
CJD). Nonprion disorders constitute about 40% of rap- this section, we focus on diffuse versus localized distribu-
idly progressive dementias, nearly half of which are due tion of atrophy or hypoperfusion and hypometabolism
to rapidly progressive variants of AD, CBD, LBD, and in major NDDs. These changes constitute the core theme
FTD. CBD and LBD are more commonly confused clini- of structural and functional imaging in NDDs.
cally with CJD. The remainder of the nonprion rapidly Alzheimer disease (Figures 8-2 through 8-5): AD
progressive dementias either are of unknown origin is the most common cause of dementia. Clinical sub-
or are caused by autoimmune or infectious disorders. types (or stages) are (1) mild cognitive impairment
Autoimmune limbic encephalitis occurs with or with- (MCI)—mild memory impairment, no cognitive defi-
out associated malignancy. cits; (2) possible AD—secondary dementia in presence
Dementia with visual symptoms: The differential of secondary disease that does impair memory but is
diagnosis can be narrowed if a patient with dementia not the likely cause; and (3) probable AD—progressive
or movement disorders also presents with visual symp- memory loss with two or more cognitive dysfunctions.
toms. The major NDDs in this category include posterior AD is characterized neuropathologically by the presence
cerebral atrophy (PCA), LBD, PSP, and CBD. Imaging of amyloid-beta peptide–containing plaques, neurofi-
features can be localized in occipital lobes and brain- brillary tangles (tau protein aggregates), and amyloid
stem. The Heidenhain variant of CJD in a patient who angiopathy. Pathologic stages are (1) transentorhinal—
presents with visual symptoms should be remembered neurofibrillary tangles in parahippocampal gyri (clini-
because diagnosis can be made by diffusion-weighted cally asymptomatic); (2) limbic stage—neurofibrillary
imaging (discussed later). tangles increase in parahippocampal gyri and develop
Parkinsonian symptoms: In patients with parkinso- in hippocampus (MCI); and (3) neocortical stage—
nian symptoms, structural imaging is sometimes needed neurofibrillary tangles in temporal and parietal lobes
to differentiate PD from Parkinson plus disorders based and eventually the rest of the cortex (severe dementia).
on certain characteristic imaging features (discussed MRI shows bilateral parietotemporal volumes loss
later). In parkinsonian disorders (e.g., IPD, MSA, PSP, with disproportionate hippocampal volumes loss,
CBD), focus on the deep gray matter, brainstem, and cer- dilated temporal horns, and choroidal fissures. Hip-
ebellum, with emphasis on the external capsule, subtha- pocampal atrophy is a marker of cognitive dysfunc-
lamic nuclei, transverse pontine fibers, and cerebellum. tion, and the rate of this atrophy is higher in AD than
Do not forget associated dementia in these disorders, in controls and MCI. Atrophy of the posterior cingulate
which is thought to be predominantly subcortical but gyrus is an early finding of AD, and is possibly related
can have associated cerebral volume loss. to loss of afferent input from associated fibers since it is
Nonparkinson movement disorders: Examples not a site of primary pathology. MR spectroscopy shows
include Huntington chorea, dystonias, etc. decreased NAA and increased myoinositol and choline
Progressive atrophy and weakness: Example is ALS. in the medial temporal lobes and, to some extent, the
Evaluate the corticospinal tract, including the brainstem parietal lobes. These metabolites are hypothesized to be
and spinal cord, for T2 signal changes. surrogate markers of neuronal loss and increased glial
Spastic paraplegia without amyotrophy: Example is activity in patients with AD.
primary lateral sclerosis. Evaluate corticospinal tract for Positron emission tomography (PET) is a well-­
atrophy due to the long-standing course of the disease. established imaging modality for evaluation of AD.
 Chapter 8 Neurodegenerative Disorders 337

tional studies on voxel-by-voxel basis, individual brain

SECTION III
images need to be transformed into a standard coordinate
system with various methods, such as statistical paramet-
ric maps, easy Z-score imaging system, and NEUROSTAT.
The major advantages of these morphometric methods are
better intersubject comparisons and much higher sensitiv-
ity and specificity. PET can identify preclinical AD cases
with a strong family history, particularly with the apolipo-
protein E ε4 allele, which is a risk factor for familial AD.
Amyloid PET imaging is being used for the diagno-
sis of AD. Multiple radioligands have been introduced,
including 18F-FDDNP, 11C-PIB (Pittsburgh B com-
pound), SB13, FPIB, and 11C-BF-227. Pittsburgh B com-
pound and 18FDDNP are more studied and are shown to
be more useful in the diagnosis of clinical and preclini-
cal AD. Global increased retention of amyloid ligands
occurs predominantly in the frontal and temporopari-
etal association areas, posterior cingulated gyrus, and
caudate nuclei, with no significant increased retention in
white matter, cerebellum, brainstem, sensorimotor cor-
tex, and medial temporal lobes compared to the normal
controls. Recall that medial temporal lobe atrophy deter-
mines cognitive dysfunction rather than amyloid deposi-
tion. Also of note, there is not a 1:1 correlation between
the presence of brain amyloid and AD. Significant amy-
loid accumulation can be present in the absence of AD,
and not all AD patients have large amyloid deposits.
Figure 8-2 Alzheimer disease. Coronal T1 serial imaging showing Despite these findings, amyloid binding agents hold
progressive medial temporal lobe atrophy. (From Whitwell JL, Jack CR
Jr. Neuroimaging in dementia. Neurol Clin 2007;25(3):843-857, viii.) great promise as a potential tool for the diagnosis of AD.
Posterior cortical atrophy (Benson’s syndrome)
(Figure 8-6): A rare early-onset dementing syndrome
Regional cerebral glucose metabolism using PET 18F-flu- with predominant and progressive visual symptoms
orodeoxyglucose (FDG) in AD shows characteristic and later development of complex symptoms such as
reductions in neocortical association areas, including the ocular apraxia (Balint syndrome) and agraphia (Gerst-
posterior cingulate, precuneus, and temporoparietal and mann syndrome). Language, memory, insight, and judg-
frontal association regions. The primary visual cortex, sen- ment remain relatively preserved until late in the course
sorimotor cortex, basal ganglia, and cerebellum are rela- of the disease. A number of different neuropathologic
tively unaffected. Remember that there is no consistent disorders are associated with posterior cortical atrophy.
concordance between PET and histopathologic regional PCA is mostly associated with histopathologic changes
findings suggesting complex pathophysiology, mainly syn- similar to those found in AD and therefore is consid-
aptic dysfunction. The sensitivity and specificity for diag- ered a subtype of AD. Typically bilateral parietooccipital
nosis of AD is greater than 80% with both single-photon atrophy is demonstrated on MRI and computed tomog-
emission computed tomography (SPECT) and PET stud- raphy (CT). SPECT and PET show deficits of perfusion
ies, but the cost ­effectiveness is debatable. To analyze func- and metabolism in both parietal and occipital lobes.

A B C
Figure 8-3 Alzheimer disease. Multiplanar 18F-fluorodeoxyglucose positron emission tomographic images showing bilateral symmetric

diminished metabolic activity in temporoparietal lobes but normal activity in occipital lobes (partially shown).
338 Section III  Problem Solving: Disease Categories

11C-PIB

HC-1 HC-2 HC-3 AD

Plaque Progression

Stage A Stage B Stage C

Figure 8-4 Alzheimer disease (AD). Sagittal positron emission tomographic images showing regional uptake of [11C]-Pittsburgh compound B
(PIB) reflecting amyloid (A) burden in the brain in three asymptomatic healthy age-matched control subjects (HC1 to 3) and one patient with
Alzheimer disease (AD; top), and schematics showing the stages of amyloid deposition in the human brain as proposed by Braak and Braak (bottom).
All AD subjects matched stage C. About 20% of HC can have A deposition ranging from stage A to C. (From Rowe CC, Ng S, Ackermann U, et al.
Imaging beta-amyloid burden in aging and dementia. Neurology 2007;68(20):1718-1725.)

Figure 8-5 Alzheimer disease. Diagnostic Z-score mapping using normal database. Patient’s positron emission tomographic image set com-
pared with similarly processed normal patients database. Deviations of regional metabolic activity from normal values is expressed as Z scores
(bottom row). (From Minoshima S. Imaging Alzheimer’s disease: clinical applications. Neuroimaging Clin N Am 2003;13(4):769-780.)
 Chapter 8 Neurodegenerative Disorders 339

Dementia with Lewy bodies (Figure 8-7): Cortical campal regions with sparing of the superior temporal

SECTION III
neurodegenerative disease with established clinical cri- lobe (“temporal dominant FTD”). A new variant called
teria. Generally, more diffuse cerebral volume loss is logopenic progressive aphasia presents with a slow rate of
present compared to AD. The neuropathologic findings speech output and word-finding pauses. In addition, the
in DLB, a condition that may account for up to 15% atrophy is more posterior, including angular gyrus and
of dementia, frequently include amyloid-beta plaques posterior aspects of the middle temporal gyrus and supe-
and neurofibrillary tangles. Therefore, some authors rior temporal sulcus. Primary progressive aphasia, a more
prefer the term Lewy body variant of AD. Medial tempo- common term, overlaps with progressive nonfluent apha-
ral lobe atrophy is less prominent, particularly in the sia and SD. Some consider primary progressive aphasia to
mesial temporal lobes (hippocampus and parahippo- be the primary disorder and the other three its subtypes.
campal gyrus). Hypoperfusion and hypometabolism Absence of frontotemporal atrophy does not exclude
on SPECT and PET imaging are consistently found in the diagnosis of FTD. The occipital lobes are almost
the occipital cortex, primarily in association with visual always spared. Hypometabolism and hypoperfusion
areas, and in the posterior parietal cortex, especially the seen on functional studies correspond to the atrophy.
precuneus. Volume loss in these areas does not account FDG patterns can vary in the three aphasia subtypes.
for the hypoperfusion, and demonstration of choliner- Typically left temporoparietal hypometabolism is seen
gic receptor changes in the occipital lobe suggests that in logopenic progressive aphasia, left frontal hypome-
cholinergic loss may be important. tabolism in progressive nonfluent aphasia, and left ante-
Frontotemporal lobar degeneration (FTLD) (Figures rior temporal hypometabolism in SD.
8-8 and 8-9): Commonly referred to as ­frontotemporal Neuronal intermediate filament inclusion disease is
dementia (FTD), of which Pick disease is a pathologic a neuropathologically distinct, clinically heterogeneous
variant. Like AD, FTD is a tauopathy. About 20% of cases variant of FTD; parkinsonism is one of the presenta-
of presenile dementia are due to FTD. Another type of tions. Frontotemporal and caudate atrophy is common.
inclusion is only labeled by anti-ubiquitin antibodies, Vascular dementia (Figure 8-10): Also termed vas-
thus isolating a subgroup of frontotemporal dementia cular cognitive disorder. Generally considered the second
(FTDu, an ubiquitinopathy), which sometimes is familial most common cause of dementia in the elderly. Diagno-
and sometimes is associated with ALS. FTD is a syndromic sis is dependent on the presence of risk factors for isch-
diagnosis that includes at least three clinical variants: emic cerebrovascular disease and temporal relationship
behavioral variant FTD or the classic FTD; semantic of dementia to cerebrovascular events, focal neurologic
dementia (SD); and progressive nonfluent aphasia. deficits, and evidence of ischemic changes on imag-
Behavioral variant FTD causes bifrontal marked atro- ing. Based on pathophysiology, vascular dementia can
phy with hypometabolism predominantly in the ventro- be divided into macroangiopathic (large-vessel disease
medial medial frontal region, anterior cingulate gyrus, with large cortical infarcts), microangiopathic (small-
anterior corpus callosum, and dorsolateral prefrontal vessel disease with lacunar infarcts), and microhem-
cortex. However, the findings may be more widespread orrhagic (multifocal small hemosiderin parenchymal
or may be within the normal range on the other extreme deposits). Sequelae of large-vessel disease result in large
(the latter subgroup may have a more benign course). discrete defects in the brain parenchyma on structural
Progressive nonfluent aphasia shows dominant perisyl- and functional imaging: multiple infarcts (multiinfarct
vian atrophy. SD typically shows severe bilateral volume dementia) or single stroke dementia (strategic stroke
loss of the inferolateral temporal pole and parahippo- vascular dementia).

A B
Figure 8-6 Posterior cortical atrophy. Axial and medial sagittal 18F-fluorodeoxyglucose positron emission tomographic images showing bilat-
eral symmetric diffuse hypometabolism in the occipital and adjacent parietal lobes.
340 Section III  Problem Solving: Disease Categories

A B C
Figure 8-7 Dementia with Lewy body. A, B: Global hypometabolism including occipital lobes on 18F-fluorodeoxyglucose positron emission
tomographic scan. C: Axial T1 magnetic resonance image showing no occipital atrophy.

A B
Figure 8-8 Frontotemporal dementia. Axial T1 and T2 images demonstrating bilateral selective anterior frontal cortical atrophy, greater on
the right side. (From Gallucci M, Limbucci N, Catalucci A, Caulo M.Neurodegenerative diseases. Radiol Clin North Am 2008;46(4):799-817, vii.)

Striatal and particularly thalamic infarcts are easily (PDD) is considered a distinct entity from AD. Neu­
identified on MRI or CT. They can account for significant ropathologically, it is characterized by the degeneration
cognitive and behavioral dysfunction due to impaired of populations of nerve cells that develop filamentous
striatocortical and thalamocortical circuitry, particularly inclusions in the form of Lewy bodies and Lewy neurites.
in the premotor frontal cortex. Several white matter These inclusions are made of the tubular filamentous
grading scales for quantitating the degree of vascular dis- nonsoluble protein alpha-synuclein. PD demonstrates
ease have been developed. The methods range from very volume loss predominantly in the frontal lobes, whereas
simple assessments to highly detailed regional quantita- PDD affects temoroparietal as well as occipital regions
tive measures. Additionally, software methodologies for but less prominent medial temporal lobe/hippocampal
assessment of the total degree of white matter changes volume loss than AD and DLB.
are available. What role these methods will play in the The pattern of glucose hypometabolism on FDG PET
everyday assessment of clinical patients with potential in PDD resembles AD-dominant hypometabolism in
vascular-based dementia is unclear. the temporoparietal regions, predominantly in the pari-
Idiopathic Parkinson disease (Figures 8-11 and etal lobes (angular gyrus), in addition to global hypo-
8-12): Cognitive impairment and neuropsychiatric metabolism.
symptoms are frequent in PD, with a 70% cumulative Presynaptic denervation is the underlying patho-
incidence of dementia. Parkinson disease with dementia genesis of IPD. 18F-6-Fluorodopa on PET imaging as a
 Chapter 8 Neurodegenerative Disorders 341

SECTION III
A B

C D
Figure 8-9 Frontotemporal dementia. Multiplanar 18F-fluorodeoxyglucose positron emission tomographic images showing bilateral symmetric
frontal and temporal lobes hypometabolism.

marker of dopamine synthesis shows decreased striatal but ­cannot clearly differentiate PD from other parkin-
uptake, mainly in the posterior putamina, that is asym- sonian disorders.
metric early in the course of the disease. Uptake is pro- Multisystem atrophy (Figure 8-13): A sporadic, pro-
portional to the severity of motor deficits. Radiotracer gressive, neurodegenerative disease of undetermined
imaging of dopamine transporter (DAT) using SPECT- etiology. Parkinsonian features dominate in more than
(FP-CIT, beta-CIT, IPT, TRODAT) or PET-(11C CFT) 80% of patients with MSA, broadly termed as MSA-P,
provides a marker for presynaptic dopamine reuptake. whereas cerebellar features dominate in 20% to 50%,
Striatal DAT ligand SPECT uptake is markedly reduced termed MSA-C. The latter presents with gait ataxia, dys-
in PD. Brain imaging with DAT ligands helps to deter- arthria, akinetic limb ataxia, and cerebellar oculomotor
mine whether drug-induced parkinsonism is entirely disturbance. MSA patients also have autonomic failure
drug induced or is an exacerbation of subclinical PD. in the form of orthostatic hypotension and genitouri-
About 10% to 15% of the cases diagnosed as early PD nary/gastrointestinal disturbances. If autonomic failure
may have normal SPECT scans termed as “subjects with predominates, MSA is known as Shy-Drager syndrome. If
scans without evidence of dopaminergic deficit” and parkinsonism predominates, it is known as striatonigral
generally are determined to be non-PD cases. How- degeneration (SND). If cerebellar ataxia predominates,
ever, functional imaging has the potential to detect pre- MSA is known as sporadic olivopontocerebellar atrophy.
clinical disease in relatives of PD patients because the Although cognitive dysfunction may appear minimal,
clinical manifestations require significantly low levels most patients experience frontal system impairment, and
of dopaminergic dysfunction. Postsynaptic dopami- many develop dementia late in the course of the disease.
nergic (D2 receptor) imaging with SPECT-IBZM and Diffuse progressive cortical atrophy is seen particularly
PET-11C-raclopride also shows decreased striatal uptake in the SND subtype, with some frontal lobe dominance.
342 Section III  Problem Solving: Disease Categories

A B
Figure 8-10 Vascular dementia. A: Axial fluid-attenuated inversion recovery image of vasculopathy and clinical diagnosis of multiinfarct
dementia showing white matter change and right remote lateral occipital infarct. B: Axial T2 image showing typical pontine small vessel ischemic
sequela as well as chronic occlusion of left internal carotid artery lacking normal flow void.

A B C
Figure 8-11 Idiopathic Parkinson disease. Magnified axial T2 images showing normal width of substantia nigra (A, B) and marked attenuation
(C) in a patient with Parkinson disease.

There is characteristic subcortical and infratentorial Progressive supranuclear palsy (Figure 8-14): PSP
atrophy but overlaps in the clinical subtypes and even is a rare brain disorder that causes serious and perma-
some overlap with PD. Pontine flattening is seen on sag- nent problems with control of gait and balance. The
ittal imaging. Decreased anteroposterior diameter of the prominent clinical manifestation is an inability to aim
pons and middle cerebellar peduncles on axial imaging the eyes properly, resulting in visual symptoms. PSP
is generally seen. “Hot cross bun sign” is a pontine cru- patients often show alterations of mood and behavior,
ciform hyperintensity on axial T2 imaging that reflects including depression and apathy, as well as progressive
degeneration of transverse pontine fibers. Brachium mild dementia. Midbrain atrophy and periaqueductal
pontis, cerebellar hemispheric, and vermian atrophy T2 hyperintensity in the tegmentum and tectum of the
is a dominant feature of sporadic olivopontocerebel- brainstem are fairly characteristic features of PSP. Atro-
lar atrophy. Bilateral T2 hyperintensities in the pon- phy of the thalamus, striatum, and frontal cortex is also
tine base and brachium pontis is an additional feature seen. Midbrain structures are more atrophied in PSP
relatively specific to MSA compared to PD. Dorsolateral than in CBD. Typical (but not pathognomonic) find-
putaminal T2 hypointensity with lateral rim “slit-like” ings in PSP are decreased metabolism and flow in the
T2 hyperintensity reflects putaminal volume loss and/or frontal lobes (hypofrontalism), particularly the medial
gliosis and is more frequent in SND subtype. frontal lobes.
 Chapter 8 Neurodegenerative Disorders 343

SECTION III
A B
Figure 8-12 Idiopathic Parkinson disease. A: Normal striata visualized by 123I-β-CIT SPECT. Regions of interest include the whole striatum as
well as the putamen and caudate nucleus separately. Cerebellum used as a reference region. B: Striata of a patient with Parkinson disease. Note
interstriatal asymmetry and predominance of putaminal degeneration. (From Eerola J, Tienari PJ, Kaakkola S, Nikkinen P, Launes J. How useful
is [123I]beta-CIT SPECT in clinical practice? J Neurol Neurosurg Psychiatry 2005;76(9):1211-1216.)

A B C
Figure 8-13 Multisystem atrophy. A: Lateral putaminal rim T2 hyperintensity on axial fluid-attenuated inversion recovery image. B: Axial T2
image showing faintly visualized transverse pontine fibers hyperintensity due to degeneration (“hot cross bun sign”). C: Midline sagittal T1 image
showing ventral pontine flattening due to atrophy.

Corticobasal degeneration (Figure 8-15): Cortico­ (GABA)ergic neurons of basal ganglia. Presents with
basal ganglionic degeneration is a rare progressive the triad of dementia, choreoathetosis, and psychosis.
neurologic disorder characterized by a combination of MRI shows diffuse cerebral atrophy with frontal lobe
parkinsonism and cortical dysfunction with strikingly dominance. The characteristic imaging feature is bilat-
asymmetric features. CBD appears to be closely related eral caudate nuclear atrophy, which is objectively mea-
to PSP in clinical, pathologic, and genetic terms. In sured by calculating the ratio of intercaudate distance
CBD, cognitive symptoms dominate, whereas in PSP, to the distance between the lateral margins of the fron-
eye movement symptoms dominate. Eye movement tal horns or inner tables; the latter is more specific and
abnormalities are common, as in PSP, and a supranu- sensitive. Putaminal atrophy is another major imaging
clear gaze palsy can be seen, as in PSP. Parasagittal and feature. Decreased FDG uptake in the basal ganglia can
paracentral atrophy (perirolandic gyri) is a distinctive be seen before the development of atrophy and can be
feature of CBD and distinguishes it from AD. Asymmet- used in gene-positive patients at risk for Huntington
ric parietal and dorsal frontal atrophy (contralateral to disease.
the side more severely affected), third ventricle dilata- Amyotrophic lateral sclerosis (Figure 8-17): Also
tion, and lenticular T2 hypointensity are useful aids to called Lou Gehrig disease. A rapidly progressive, invari-
careful clinical evaluation. Hyperintensity in the subcor- ably fatal neurologic disease affecting upper and lower
tical white matter in the rolandic region on fluid-atten- motor neurons. The muscles gradually weaken, waste
uated inversion recovery (FLAIR) images, asymmetric away, and twitch. Degeneration of the corticospinal
midbrain, and cerebral peduncle atrophy may be pres- tract is manifested by posterior limb internal cap-
ent. Asymmetric glucose hypometabolism and 18F-dopa sule and white matter T2 and FLAIR hyperintensities;
uptake are seen on PET imaging in the parietal lobe, internal capsule hyperintensity is a specific sign on
striatum and thalamus. PD images. Hypointense line along the posterior rim
Huntington disease (Figure 8-16): Autosomal of the precentral gyri gray matter is seen in patients
dominant NDD with loss of γ-aminobutyric acid with ALS. Subcortical white matter T2 hyperintensity
344 Section III  Problem Solving: Disease Categories

A B
Figure 8-14 Progressive supranuclear palsy. A: Midline sagittal T1 image showing pontomesencephalic disproportion with marked midbrain
atrophy resulting in a penguin or hummingbird profile. B: Mickey Mouse sign on axial T1 midbrain image.

is a useful sign in clinically verified ALS and is bet- Problem Solving: Reversible versus
ter seen on FLAIR images, but both of these signs can Irreversible Dementia (Figures 8-18
also be seen in normal older patients. Hyperintense
through 8-21)
T2 changes in the body of the corpus callosum rep-
resent degeneration of the commissural fibers inter- One of the most important roles of structural imaging is
connecting the motor cortices bilaterally. Progressive ruling out dementia mimickers. Reversible dementia is
symmetric frontotemporal atrophy, particularly of a relative term, because some disorders included in this
the sensorimotor strip, is seen in ALS with or with- category may not be completely reversible. The percent-
out dementia (termed ALSD). Typically, bifrontal but ages of reversibility in dementia vary, up to 23% for par-
more extensive hemispheric hypometabolism and tial reversal and up to 10% for full reversal. Depression,
hypoperfusion can be demonstrated on SPECT and drug intoxication, and metabolic and neurosurgical dis-
PET studies. orders are the major causes of reversible dementia.

A B C
Figure 8-15 Corticobasal degeneration. A: Axial computed tomographic image showing asymmetric left parietal cortical atrophy. Axial fluid-
attenuated inversion recovery (B) and T2 (C) images in another patient showing symmetric parietal atrophy. (From Gallucci M, Limbucci N,
Catalucci A, Caulo M. Neurodegenerative diseases. Radiol Clin North Am 2008;46(4):799-817, vii.)
 Chapter 8 Neurodegenerative Disorders 345

are seen in dementia due to vitamin B12 deficiency and

SECTION III
hypothyroidism.
Infectious dementia is seen less frequently now,
although a resurgence has taken place in the past three
decades with the emergence of acquired immunodefi-
ciency syndrome (AIDS) and variant CJD. Endemic or
high-risk groups or dementia at younger ages warrants
workup for an infectious etiology. Human immunodefi-
ciency virus (HIV) dementia, also known as AIDS demen-
tia complex, an AIDS defining illness, is caused by direct
infection of the macrophages and microglia of the central
nervous system by the HIV retrovirus, with likely indirect
neurotoxic effects on the neurons. The most common
imaging feature is a generalized cortical atrophy, which
is unusual for younger patients. Diffuse patchy white
matter T2 hyperintensity is another prominent feature,
mainly in the peritrigonal and subinsular regions. The
incidence of HIV dementia is reduced from about 20%
to 5% after introduction of highly active antiretroviral
therapy (HAART). A severe form of nonspecific leukoen-
cephalopathy can be seen in patients who do not respond
to HAART. Neurosyphilis, a somewhat forgotten disease
Figure 8-16 Huntington disease. Axial computed tomographic in the western world, is caused by Treponema pallidum,
image demonstrating typical bilateral frontal horn lateral flattening which invades the central nervous system early in the
due to caudate atrophy. course of disease but causes persistent infection in only
a subset of infected persons. Individuals with persistent
infection or asymptomatic meningitis are at risk for devel-
Imaging is negative in most of these conditions except oping symptomatic neurosyphilis. The forms of presenta-
for neurosurgical conditions, which comprise subdu- tion of neurosyphilis can be grouped in two categories:
ral hematoma (typically, chronic subdural hematomas early (asymptomatic, meningeal, and meningovascular
with rebleeds and fluctuating mental status), normal neurosyphilis) and late (progressive general paralysis or
pressure hydrocephalus, and intracranial tumors (e.g., dementia paralytica and tabes dorsalis). Meningovascular
anterior fossa large olfactory groove meningioma). This type manifests as subacute encephalitis syndrome with
group of disorders also validates the cost effective use of vasculitis pattern causing infarcts that result in demen-
noncontrast CT head for workup of dementias. tia. Dementia paralytica shows diffuse cerebral atrophy
Alcohol is a common identifiable cause of cognitive predominantly in the mesial temporal lobes. Mesial tem-
dysfunction. Amnestic syndrome, alcohol dementia, poral T2 hyperintensity may be present in addition to
and Wernicke-Korsakoff syndrome (WKS) constitute nonspecific white matter T2 changes. T2 signal changes
distinct entities. Diffuse cerebellar atrophy is a con- improve after penicillin therapy. Lyme disease can result
sistent marker of alcohol abuse. Specifically, look for in frontal dementia with subcortical degeneration.
mamillary bodies atrophy in chronic cases of Wernicke- CJD, a rapidly progressive and fatal disease, is caused
Korsakoff syndrome. No specific brain imaging findings by a protease-resistant prion protein. A characteristic

A B C
Figure 8-17 Amyotrophic lateral sclerosis. A: Axial T2 image showing bilateral corticospinal tract (CST) hyperintensities. B: Sagittal T2 image
showing subcortical CST hyperintensity. C: Axial T2 image demonstrating bilateral motor cortex diffuse hypointensity.
346 Section III  Problem Solving: Disease Categories

A B

C D
Figure 8-18 Normal pressure hydrocephalus. A: Coronal T1 image showing callosal angle (CA <90 degrees). Mean CA is 65 degrees with
semantic dementia of 15 degrees compared to 105 degrees in Alzheimer disease. B: Axial T2 image demonstrating measurement of the Evan ratio
(>0.3). C, D: Sagittal midline representative images from cine cerebrospinal fluid (CSF) flow study showing subjective evidence of robust aque-
ductal CSF flow (alternating phases manifested by black and white colors).
 Chapter 8 Neurodegenerative Disorders 347

SECTION III
A B

C D
Figure 8-19 Wernicke’s encephalopathy. Axial fluid-attenuated inversion recovery image (A) showing hypothalamic and axial T2 image
(B) showing periaqueductal T2 hyperintensity in an acute case of Wernicke encephalopathy. C, D: A chronic case showing severe mamillary body
atrophy on sagittal and axial imaging. Note that mamillary bodies are consistently seen in normal patients.
348 Section III  Problem Solving: Disease Categories

A B
Figure 8-20 Creutzfeldt-Jakob disease. A: Axial diffusion tensor image showing bilateral typical striatal and thalamic hyperintensity in a case
of variant Creutzfeldt-Jakob disease. B: Selective bilateral parietooccipital lobe (posterior) cortical hyperintensity in another patient (Heidenhain
variant of Creutzfeldt-Jakob disease).

A B C
Figure 8-21 Neurosyphilis. Multiplanar 18F-fluorodeoxyglucose positron emission tomographic images showing nonspecific finding of global
cortical hypometabolism in a patient with dementia and neurosyphilis.

triad of myoclonus, progressive dementia, and periodic Problem Solving: Mild Cognitive
sharp-wave patterns are signs of cortical dysfunction. The Impairment to Alzheimer Disease
course of the disease is the key to suspecting CJD. CJD is (Figure 8-22)
classified into sporadic, variant, familial, and iatrogenic
types. Diffusion-weighted imaging is the MRI sequence MCI is an intermediate state between normal cog-
of choice. Interpretation pearls are to: use narrower dis- nitive aging and dementia and is a major risk factor
play windowing for DWI, focus on mesial cortices, think for dementia. Diagnosis is based on clinical criteria of
of other disorders if cortical or pial enhancement is a nondemented patient with subjective and objective
present, and recommend follow-up study if the clinical memory impairment but largely intact cognition and
suspicion is high and the current study is negative. Spo- preserved daily activities. MCI is divided into single or
radic CJD, the most common type, occurs worldwide multiple domain amnestic MCI (aMCI) and nonamnes-
and causes hyperintensity of the putamen and caudate tic MCI (naMCI). The risk is higher in aMCI progressing
nuclei. The variant form typically causes bilateral dor- to AD, with rates of 10% to 15% per year and 50% at
sal thalamic T2 hyperintensity (“pulvinar and hockey- 5 years. Other risk factors are degree of cognitive dys-
stick signs”). As in PCA, the Heidenhain variant of CJD function, presence of a specific apolipoprotein E gene
presents with visual symptoms and dementia with allele, and severity of hippocampal atrophy. About 10%
domi­nant occipital cortical diffusion hyperintensity. to 25% of MCI cases progress to dementia in 10 years;
 Chapter 8 Neurodegenerative Disorders 349

SECTION III
Figure 8-22 Amnestic mild cognitive impairment (aMCI). Top: Patterns of cortical atrophy shown on a three-dimensional surface rendering,
based on voxel-based morphometry. Bottom: Results shown on a sagittal and coronal slice through the customized template, selected to highlight
changes in the cingulate cortex and the medial temporal lobes. (From Whitwell JL, Shiung MM, Przybelski SA, et al. MRI patterns of atrophy asso-
ciated with progression to AD in amnestic mild cognitive impairment. Neurology 2008;70(7):512-520.)
350 Section III  Problem Solving: Disease Categories

RT. LAT LT. LAT RT. MED LT. MED

AD
(mild)

AD
(severe)

PDD

DLB

FTD

PSP

VD

NPH

0 7
Z-score

Figure 8-23 Dementias (three-dimensional stereotactic surface projection [3D-SSP] 18F-fluorodeoxyglucose positron emission tomography). Meta-
bolic abnormalities in various dementing disorders as demonstrated by 3D-SSP Z-score maps. Parkinson disease with dementia and dementia with Lewy
bodies show metabolic reductions similar to Alzheimer disease in the lateral cortices but additional significant metabolic reduction in the occipital cor-
tex. Frontal dominant reduction in frontotemporal dementia. Mild frontal reduction in progressive supranuclear palsy. Vascular dementia shows patchy
reduction related to ischemic foci. Normal pressure hydrocephalus (NPH) shows mild diffuse reduction. (From Minoshima S. Imaging Alzheimer’s
disease: clinical applications. Neuroimaging Clin N Am 2003;13(4):769-780.)
 Chapter 8 Neurodegenerative Disorders 351

SECTION III
DVR
3.0

1.5

0.0

HC DLB AD FTD

Figure 8-24 Amyloid imaging. Positron emission tomographic images (using distribution volume ratio) showing nonspecific Pittsburgh com-
pound B (PIB) binding in white matter in human control and frontotemporal dementia subjects compared with PIB binding in the frontal, tem-
poral, and posterior cingulate/precuneus cortex of patients with Alzheimer disease and those with dementia with Lewy bodies. (From Rowe CC,
Ng S, Ackermann U, Gong SJ, et al. Imaging beta-amyloid burden in aging and dementia. Neurology 2007;68(20):1718-1725.)

80% of them are diagnosed with AD. About one fourth ders. FTD is intermediate between focal disorders of the
of the remaining MCI cases are due to reversible condi- brain and more generalized neurodegenerative diseases.
tions, and the remaining half improve or remain stable. Some patients experience only aphasia, whereas others
Remember that MCI is an identifiable prodrome for all progress to dementia within a few years. As alluded to
dementia subtypes rather than just AD (e.g., vascular earlier, motor neuron disease develops in a subset of
dementia and Parkinson–LBD). FTD. This subgroup (FTDu) has a higher mortality rate
Voxel-based morphometry is preferably used to from FTD than other affected patients. Patients with pri-
detect and objectively measure mesial temporal atrophy. mary progressive aphasia typically have preserved mem-
More prominent medial and inferior temporal atrophy ory and visuospatial functions, whereas those with AD
is present in aMCI compared to naMCI. More extensive have nearly universal involvement of these functions. In
parietotemporal and cingulate atrophy in addition to general, the differences between FTD or its variant and
hippocampal atrophy in aMCI predicts progression to AD reflect the pathologic involvement of the frontal and
AD. Cortical thinning as a surrogate marker of cognitive temporal lobes, particularly in the left hemisphere, com-
impairment is being used in quantitative studies. pared to the early involvement of the hippocampi and
High hippocampal diffusivity is associated with a parietal lobes in AD. Besides the more common diffuse
greater risk of progression to AD in aMCI. Mesial tem- dementing disorders such as AD, FTD must be differenti-
poral metabolite pattern in aMCI is similar to AD (i.e., ated from focal processes such as brain tumors, abscesses,
decreased NAA and elevated ratios of myoinositol to and strokes on conventional structural imaging.
creatine levels). AD can present in the early stage with disproportion-
Both PET and SPECT studies show reduced blood ate frontal lobe symptoms (“frontal variant of AD”)
flow and/or glucose metabolism in the temporoparietal mimicking FTD. FDG PET as metabolic study and SPECT
lobes, hippocampus, and posterior cingulate gyrus in as perfusion study have been useful tools in clinically
MCI and represents a higher risk of progressive cognitive difficult cases of AD versus FTD, with greater than 80%
decline and thus, development of AD. Pittsburgh com- accuracy. Posterior cingulate atrophy and hypometabo-
pound B (N-methyl-[11C]2-(4′-methylaminophenyl)-6- lism are specific markers of AD. Remember that AD with
hydroxybenzothiazole ([11C]PIB) PET uptake is similar associated depression or advanced cases show bilateral
to AD, with global increased binding predominantly frontal lobe deficits on functional studies. Similarly,
in frontal association areas. These two groups of func- advanced FTD shows temporoparietal hypometabolism.
tional/molecular studies potentially can be used to Amyloid radioligands (e.g., 11C-PIB Pittsburgh B com-
identify high-risk patients in the preclinical stage. pound and 18F-BAY94-9172) are useful for differentiat-
ing FTD and AD. Generally, FTD shows no significant to
Problem Solving: FTD versus mild retention of radiotracer.
AD “Frontotemporal versus Structural imaging has a supplementary role with
Temporoparietal Dementia” the increasing use of volumetric and quantitative tech-
niques. Atrophic features favoring FTD include asym-
(Figure 8-23 and 8-24)
metric frontotemporal atrophy, usually on the left side,
The average age of onset is younger in FTD than in AD. “knife-edge atrophy” in the anterior temporal lobes (in
FTD, unlike AD, lacks cholinergic deficiency, highlighting SD subtype), left perisylvian atrophy (in progressive
the clinical significance in differentiating the two disor- non-fluent aphasia [PNF]), anterior or diffuse corpus
352 Section III  Problem Solving: Disease Categories

callosum atrophy, and anterior cingulate atrophy. AD is leptics. DLB in earlier stages is dominated by cognitive
characterized by atrophy of callosal posterior body. Gen- ­symptoms with absent or minimal parkinsonism and
erally, FTD has severe frontotemporal atrophy (left side therefore is easily confused with AD. Compared to PD,
dominant) and mild hippocampal atrophy compared to there is progressive cognitive decline with particular def-
moderate hippocampal, temporal, and mild frontal lobe icits of visuospatial ability as well as frontal executive
atrophy in AD. Remember that hippocampal atrophy can function with less prominent parkinsonism and with-
be present in both FTD and AD. out the classic parkinsonian rest tremor.
More diffuse cerebral volume loss is seen compared to
Problem Solving: Vascular AD. Relative preservation of medial temporal lobe with
Dementia versus AD “Mixed less pronounced atrophy is seen compared to AD and vas-
cular dementia. Relatively more atrophy in the midbrain,
Dementia” (Figures 8-5, 8-10, and 8-23)
substantia innominata, hypothalamus, and putamina is
The diagnosis of vascular dementia requires the presence seen in DLB compared to AD. However, medial temporal
of faster changes and the absence of causes of dementia. lobe atrophy is present and more pronounced compared
Hence, the absence rather than the presence of ischemic to normal controls, PD, and even PDD.
changes on imaging is more helpful in distinguishing vas- Occipital lobe hypoperfusion and hypometabolism are
cular dementia from AD. Diagnosis of vascular dementia major differentiating features from AD on SPECT and PET
requires the following criteria: cognitive loss, often pre- studies. FP-CIT as a marker of presynapatic dopaminergic
dominantly subcortical; vascular brain lesions demon- dysfunction may be used to differentiate DLB from AD
strated by imaging; a temporal link between stroke and with very high accuracy. However, FP-CIT should not be
dementia; and exclusion of other causes of dementia. injudiciously used in dementia patients to avoid a high
Unlike AD, executive functions are dominantly involved, incidence of false positives. Bilateral striatal diminished
with mild memory impairment. Binswanger disease or uptake on FP-CIT is a similar finding to PD and there-
subcortical chronic encephalopathy is considered a vari- fore not helpful in differentiating these two disorders.
ant of multiinfarct dementia with periventricular white 123I-Meta-iodobenzylguanidine (MIBG) cardiac uptake is

matter T2 hyperintensities typically due to incomplete significantly reduced in DLB and PD compared to AD. As
infarcts and presenting with dementia, gait, and blad- alluded to before, DLB can have amyloid deposition. Dis-
der symptoms. Cerebral amyloid angiopathy is an over- tribution of the amyloid ligands is generally similar to AD
lapped condition between vascular diseases and AD. but the degree of binding is comparatively mild and varied.
Large territory infarcts in the middle cerebral artery
(MCA) and anterior cerebral artery (ACA) distribution Problem Solving: MSA-P versus PD
result in dementia in about 30% of stroke survivors.
(Figures 8-12 and 8-25)
Superficial watershed infarcts such as superior frontal
gyrus (MCA–ACA watershed) and inferior temporal PD has a relatively long course compared to the rapid
gyrus (MCA–posterior cerebral artery watershed) can progressive course of MSA, a major component of Par-
result in cognitive dysfunction. Single stroke dementia kinson plus syndromes. Generally, a small portion of
is caused by a single strategically located infarct and usu- patients with MSA and vascular parkinsonism show an
ally affects the left hemisphere with thalamic involve- initial response to levodopa. Clinical differentiation from
ment. Small-vessel ischemic disease manifests as patchy PD can be difficult if the parkinsonism symptoms are
deep white matter and deep gray matter T2 hyperinten- dominant (MSA-P), typically due to SND. Wenning et al.
sities (complete and incomplete microvascular infarcts). showed the following clinical features suggestive of MSA:
The differentiation may be very difficult in some poor response to levodopa, autonomic features, speech
cases due to mixed AD and vascular dementia patholo- or bulbar dysfunction, absence of dementia, absence of
gies, termed mixed dementia. Subcortical T2 changes are levodopa-induced confusion, and falls. Misdiagnosis of
seen in both vascular dementia and AD; however, in MSA is usually due to its confusion with PD or PSP.
mixed dementia, large/hemispheric infarcts in addition IPD shows diffuse cerebral volume predominantly
to multiple microinfarcts are more frequent. in the temporoparietal lobes overlapping with normal
aging. In contrast, atrophy and signal changes of the
Problem Solving: DLB versus AD subcortical structures are dominant features of MSA on
and PDD (Figures 8-3, 8-5, 8-7, 8-23, structural imaging, seen as lateral putaminal slit-like T2
hyperintensity, dorsolateral putaminal T2 hyperinten-
and 8-24)
sity, dominant pontine atrophy, transverse pontine fibers
As many as 20% of elderly individuals may suffer from degeneration (“hot cross bun sign”), cerebellar atrophy,
DLB. The consensus criteria for DLB state that the cen- and middle cerebellar peduncle T2 hyperintensities as
tral feature of the condition is a progressive cognitive described above. Frontoparietal atrophy is seen in MSA.
decline accompanied by two of three additional core The pathophysiology of PD centers on striatonigral cir-
features, which include fluctuating cognition, recurrent cuitry, but conventional MRI usually is unremarkable.
visual hallucinations, and spontaneous motor features Normal laminated zones of substantia nigra on T2 imag-
of parkinsonism. LBD has often been misdiagnosed as ing show hypointense posterior pars reticulata (SNPr)
AD or vascular dementia or confused with idiopathic and hyperintense anterior pars compacta (SNPc). Axial
PDD. Diagnosis of DLB is important for clinicians T2 imaging can show decreased SNPc width. Character-
given the high incidence of adverse response to neuro- istic MSA features, such as reduced middle cerebellar
 Chapter 8 Neurodegenerative Disorders 353

SECTION III
A B

C D E
Figure 8-25 Parkinson disease, dementia with Lewy bodies, and Alzheimer disease (FP-CIT)-123I-radiolabeled 2-carbomethoxy-3-(4-
iodophenyl)-N-(3-fluoropropyl) nortropane with single-photon emission computed tomographic images. A: Healthy older control subject. B:
Subject with Alzheimer disease. C: Subject with dementia with Lewy bodies. D: Subject with Parkinson disease. E: Subject with Parkinson disease
with dementia. (From O’Brien JT, Colloby S, Fenwick J, et al. Dopamine transporter loss visualized with FP-CIT SPECT in the differential diagnosis
of dementia with Lewy bodies. Arch Neurol 2004;61(6):919-925.)

peduncle width, are useful for distinguishing patients ­ eurodegenerative PD mimickers. The findings are related
n
with MSA from those with PD. MR parkinsonian index to postganglionic cardiac sympathetic nerve denervation
based on pons and middle cerebellar peduncle area in PD and DLB compared to MSA, PSP, CBD, and AD.
ratios to midbrain and superior cerebellar peduncle
has very high accuracy in differentiating MSA from PD. Problem Solving: PSP versus PD
Increased ADC values in middle cerebellar peduncle can
(Figures 8-25 and 8-26)
add to the differentiation of MSA-P from PD.
Iodine-123 fluoropropyl (FP)-CIT is highly accurate in PSP is often misdiagnosed because some of its symp-
diagnosing neurodegenerative parkinsonism but usually toms are very much like those of PD, AD, and more rare
is not helpful in differentiating MSA from PD. Symmetric NDDs, such as CJD. The key to diagnosing PSP is iden-
or asymmetric decreased striatal uptake is seen in MSA and tifying early gait instability and difficulty in moving the
PD, with more prominent reduction of midbrain uptake eyes, the hallmark of the disease. Problems with speech
in MSA and PSP on advanced volumetric techniques. The and swallowing are much more common and severe in
tracer can be very helpful in patients with atypical charac- PSP than in PD. Tremor, almost universal in patients
teristics of parkinsonism (termed clinically uncertain par- with PD, is rare in those with PSP. Patients with PSP
kinsonian syndromes [CUPS]), excluding postsynaptic-like respond poorly and only transiently to levodopa. There
psychogenic, drug-induced, or vascular parkinsonism. is currently no effective treatment of PSP.
18F-6-Fluorodopa PET shows a greater decrease in caudate Prominent midbrain tegmentum atrophy on midsagit-
relative to putamen in MSA-P compared to PD. 123I-MIBG tal section (“penguin silhouette sign”) compared to pon-
myocardial scintigraphy is another useful tool because tine atrophy is highly accurate in differentiating PSP from
patients with PD and LBD have significantly lower cardiac PD and MSA-P; the latter shows more prominent pontine
123I-MIBG uptake than do patients with MSA and other atrophy. Remember the periaqueductal T2 hyperintensity
354 Section III  Problem Solving: Disease Categories

A B C
Figure 8-26 Midbrain profiles. Midline sagittal T1 images showing mesencephalic atrophy in progressive supranuclear palsy (A), pontine atro-
phy and flattening in multisystem atrophy (B), and normal pontomesencephalic profile in Parkinson disease (C).

seen in PSP. Increased ADC values in the putaminal and Problem Solving: ALS versus
superior cerebellar peduncles can add to the differentia- Atypical Motor Neuron Diseases
tion of PSP from PD. Increased MR parkinsonian index (Figure 8-17)
based on pons and middle cerebellar peduncle area ratios
to midbrain and superior cerebellar peduncle has very ALS may be mimicked by disorders that affect different
high accuracy in differentiating PSP from PD and MSA-P. levels of the motor system from cortex to muscle. They
Typically, decreased FDG metabolism and flow in do not fall into the clinical profile of typical ALS and
the frontal lobes (hypofrontalism) plus hypometabo- are collectively termed atypical motor neuron diseases. The
lism in the midbrain and thalami are seen compared to atypical motor neuron diseases are divided into three
dominant parietal hypometabolism in PD. Reduction of groups: (1) upper motor neuron—primary lateral scle-
medial frontal metabolism may be a valuable diagnos- rosis, hereditary spastic paresis, and lathyrism; (2) lower
tic imaging parameter in distinguishing PSP from PD. motor neuron—progressive muscular atrophy, adult-
Anterior cingulate hypoperfusion seems to be an early, onset spinal muscular atrophy (spinal muscular atrophy
distinct brain abnormality in PSP compared with PD. type IV), Kennedy disease, Hirayama disease, multifocal
Using 123I-FP-CIT, PSP patients show more severe and motor neuropathy, and postpolio muscular atrophy; and
symmetric dopamine transporter loss in the entire stria- (3) overlap syndromes—dementia and ALS, dementia
tum compared to patients with PD. parkinsonism and ALS, RPD, CJD, and ALS, and FTD
with ALS (FTDu). The distinction is primarily clinical,
Problem Solving: CBD versus PSP including electrophysiologic studies, with a limited role
of imaging. Primary lateral sclerosis shows more severe
and PD (Figures 8-14 and 8-15)
bilateral frontoparietal, particularly precentral, atrophy
CBD is difficult to diagnose in the early stages (<50% due to a prolonged course of primary lateral sclerosis
sensitivity) and more commonly is confused with PSP. compared to ALS. FTDu is closely related to ALS, with
CBD shares the same tau haplotype as PSP patients, dominant frontotemporal dysfunction. Dementia is
suggesting that both CBD and PSP share the same more common in western pacific-type ALS; however, it
genetic background and possibly the same pathologic can also be seen in classic sporadic and familial types
mechanism. CBD patients do not respond to levodopa (ALS-D). ALS is now grouped together with ALS-D, FTLD-
treatment. Management is mainly supportive. In CBD, U, and ALS/parkinsonism–dementia complex of Guam
cortical involvement results in dominant cognitive and and Kii as TDP-43 proteinopathy. Pure imaging mimick-
other cortical dysfunctions compared to impaired eye ers of ALS include bilateral wallerian degeneration with
movement in PSP. Assessment of orofacial apraxias can atrophy and T2 hyperintensity of the corticospinal tract,
aid in the clinical differentiation of CBD from PD, PSP, typically due to proximal ischemic or demyelinating
LBD, and MSA, reflecting involvement of supplemen- lesions. A pitfall to remember is normal corticospinal
tary motor areas and the superior parietal lobule. Clin- tract hyperintensity on 3-T and higher field systems.
ical findings in CBD are more commonly asymmetric.
Asymmetry is also a key imaging feature. Usually SUMMARY OF CHARACTERISTIC
asymmetric frontoparietal atrophy is seen and in combi-
IMAGING FEATURES IN NDDS
nation with lack of midbrain atrophy helps in differen-
tiating PSP and PD. Asymmetric atrophy of the cerebral Atrophy
peduncles and midbrain is also seen. Functional stud-
ies show asymmetric hemispheric cortical glucose Diffuse parenchymal volume loss may be seen in any
­metabolism and decreased 18F-dopa uptake in the pari- NDD. Imaging characteristics based on symmetry and
etal lobe, striatum, and thalamus. preferential involvement are enumerated as follows.
 Chapter 8 Neurodegenerative Disorders 355

Dominant cortical atrophy: AD, LBD, FTLD Frontal lobes (hypofrontalism): PSP, frontal variants

SECTION III
Dominant subcortical atrophy: Putamina in MSA, of FTLD and AD
caudate nuclei in Huntington disease Occipital lobes: DLB and PCA
Nonselective diffuse atrophy: Aging, PD, any other
NDD in advanced stages Specific Radiotracer Uptake
Selective atrophy: Bilateral parietotemporal in AD,
bilateral frontotemporal in FTLD and ALS. Local- 18F-6 Fluorodopa: Marker of presynaptic dopamine
ized pontocerebellar atrophy in MSA(sporadic synthesis. Bilateral decreased posterior putaminal
olivopontocerebellar atrophy) or midbrain teg- uptake in IPD, asymmetric in early course, asymmetry
mental atrophy in PSP can be related to increased uptake due to up-regula-
Asymmetric atrophy: Asymmetric frontoparietal tion of receptors. Usually similar findings in atypical
hemispheric atrophy in CBD; FTLD subtypes can Parkinson disorders (e.g., MSA, PSP, CBD).
show asymmetric atrophy DAT ligands: Marker of presynaptic dopaminergic dys-
Side dominant atrophy: Left side dominant anterior function as seen in neurodegenerative Parkinson disor-
temporal and perisylvian atrophy in SD and pro- ders. Generally does not differentiate IPD from atypical
gressive non-fluent aphasia (PNFA), subtypes of Parkinson disorders. Bilateral striatal decreased uptake
FTLD, respectively in PD (putaminal uptake more reduced than caudate).
Uptake may be asymmetric in early course of disease.
Striatal reduced uptake (caudate greater than putam-
T2 White Matter Hyperintensities
ina) in MSA and PSP plus more prominent midbrain
Common finding in advanced age compromising its reduction compared to PD. More extensive diminished
specificity for NDDs. Multiple sclerosis is included uptake in LBD with left hemispheric asymmetry com-
because of its common incidence and as an important mon. Reduced striatal uptake helpful in differentiating
imaging differential diagnosis. from AD. Uptake is generally normal in essential tremor.
Multiple sclerosis: Pericallosal, perithalamic, cal- Pittsburgh B compound: AD shows global increased
losal, anterior temporal periventricular, brachium retention of amyloid ligands predominantly in fron-
pontis, and brainstem surface typical locations. Per- tal and temporoparietal association areas, posterior
pendicular direction relative to corpus callosum. cingulate gyrus, and caudate nuclei with no significant
Laminated T2 architecture, also referred to as sur- increased retention in white matter, cerebellum, brain-
rounding dirty white matter. Edge enhancement. stem, sensorimotor cortex, and medial temporal lobes.
Binswanger disease: Overlapped features. Dominant FTD: No significant radiotracer retention.
deep white matter patchy T2 hyperintensities com- DLB: Similar to AD but with milder degree of radio-
pared to well-defined T1 hypointense complete tracer retention.
microvascular infarcts (lacunes) mostly in the deep
gray matter. Specific Imaging Signs in NDDs
CADASIL (cerebral autosomal dominant arteriopa-
thy with subcortical infarcts and leukoencephalop- Hot cross bun sign (Figure 8-13, A): Cruciform hyper-
athy): Confluent white matter T2 hyperintensity in intensity sign is due to selective loss of myelinated
the periventricular white matter, extension into bilat- transverse pontocerebellar pontine tegmentum and
eral external capsules, internal capsules, and anterior corticospinal tracts. The sign is highly specific to
temporal pole with sparing of frontoorbital white MSA-C in differential diagnosis from PD and MSA-P.
matter. Striatocapsular lacunae. Microhemorrhages. Hyperintense putaminal rim sign (Figure 8-13, C):
ALS: Bilateral corticospinal tract hyperintensity HPR is a specific sign for MSA in a proper clinical set-
including precentral gyrus subcortical white matter ting and has a high negative predictive value. HPR is
and sometimes in ventral spinal cord. commonly seen in normal old-age patients on 3-T sys-
tems, attributed to differential putaminal iron deposi-
tion rather than true pathologic rim hyperintensity.
Putaminal T2 Hypointensity
Rarely seen in other NDDs (e.g., CBD, PSP, old-age
Bilateral putaminal T2/T2* hypointensity in combina- PD). HPR is caused by a combination of gliosis and
tion with hyperintense putaminal rim (HPR) is a specific extracellular interstitial fluid due to atrophy. Presence
marker of MSA in presenile patients. Bilateral putam- of HPR on FLAIR imaging likely indicates gliosis, dif-
inal and globus pallidus T2 hypointensity is commonly ferentiating MSA from false positives.
seen in normal old-age subjects and in other NDDs due Penguin silhouette and Mickey Mouse signs (Figure
to increasing use of susceptibility-weighted imaging. 8-14): Signs relatively specific to PSP. Penguin or
hummingbird side profile appearance on midsagittal
Hypoperfusion and image highlights the hallmark morphologic change
in PSP (i.e., midbrain atrophy). Axial image of the
Hypometabolism
midbrain looks like Mickey Mouse and is due to
Diffuse hypometabolism and hypoperfusion may be seen dominant midbrain tegmentum atrophy and sparing
in any of the NDDs particularly in the advanced stages. of cerebral peduncles and tectum.
Temporoparietal: MCI, AD, PD/PDD Pulvinar and hockey-stick signs (Figure 8-20): Bilateral
Frontotemporal: FTD, ALS, and advanced AD with dorsal thalamic focal hyperintensities on T2, FLAIR,
diffuse hypometabolism and hypoperfusion and diffusion-weighted imaging sequences result in
356 Section III  Problem Solving: Disease Categories

ism is seen predominantly in adult-onset patients

whereas dystonia seems to occur more frequently in
earlier-onset cases. The pallidal central hyperintensity
of the eye sign may develop before rim hypointensity
in patients with mutations. The term ­neurodegeneration
with brain iron accumulation (NBIA) has replaced the
eponym Hallervorden-Spatz disease. NBIA is a hetero-
geneous group of progressive extrapyramidal disor-
ders characterized by ­neurodegeneration and excessive
focal iron accumulation in the basal ganglia due to
spheroid neuronal degeneration. The known causes of
NBIA include pantothenate kinase-associated neuro-
degeneration, neuroferritinopathy, infantile neuroax-
onal dystrophy, and aceruloplasminemia.
Face of the giant panda sign (Figure 8-28): Consists of
high signal intensity in the tegmentum except for red
nucleus, preservation of signal intensity at the lateral
portion of the pars reticulata of the substantia nigra,
and hypointensity of the superior colliculus. It is one
of the specific imaging findings in Wilson disease.

Suggested Readings
Figure 8-27 Tiger-eye sign. Axial FSE T2 image showing bilateral
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 chapter 9

Infection/Inflammation
Majda M. Thurnher, Julia Frühwald-Pallamar, and Stefan B. Puchner

Infection involving the brain is considered an emer- neurologic signs, or impaired consciousness. A CSF
gency that requires rapid and accurate diagnosis, absolute neutrophil count greater than 1,000/mm3 is
followed by an appropriate surgical and medical inter- predictive of bacterial meningitis.
vention. Because of the potentially devastating neuro-
logic deficits, it is imperative to image patients with Pyogenic Meningitis
clinical suspicion of infectious disease of the central ner-
vous system (CNS). The development of an intracranial CT and magnetic resonance imaging (MRI) can be nor-
infection is dependent on the virulence of the organism mal in early cases of meningitis. Meningeal enhancement
and the host’s immune system. Some of the CNS infec- usually is seen on postcontrast MR sequences, which
tions, such as invasive aspergillosis, are among the most are more sensitive than CT. Fluid-attenuated inversion
frequent, frightening, and life-threatening opportunistic recovery (FLAIR) MRI has proved to be of great value in
infections in immunocompromised patients. Although the detection of meningeal diseases, with high signal in
the management of patients with suspected CNS infec- the subarachnoid spaces that reflects a high protein con-
tions has been revolutionized in recent years with new tent in the CSF, which causes a decrease in T1 relaxation
and better antiviral and immunomodulatory therapies, time and results in hyperintensity (Figure 9-1). The dif-
the frequency of CNS infections is not declining. The ferential diagnosis includes leptomeningeal carcinoma-
increasing number of immunocompromised patients tosis and subarachnoid hemorrhage. Communicating
who may have CNS infections as a result of acquired hydrocephalus is the most common complication of
immunodeficiency syndrome (AIDS) as well as organ meningitis, with the inflammatory debris obstructing the
transplantation and bone marrow transplantation flow and reabsorption of CSF. A serious complication of
(BMT) presents new challenges to clinicians and radi- pyogenic meningitis is pyogenic ventriculitis, which can
ologists. be recognized on imaging as periventricular high signal
This chapter outlines the major clinical and key intensity on FLAIR MRI, ependymal enhancement on
radiologic findings in infections of the CNS. postcontrast images, and fluid–fluid levels in the ven-
tricles. The presence of ventricular debris will be seen
in the dependent parts of the ventricles as a nonlinear
MENINGITIS
fluid–fluid interface on T1-weighted imaging (T1-WI).
Streptococcus pneumoniae is found in 50% of cases of adult In acute blood, a straight level will be seen. In pyocepha-
meningitis. Other common organisms that cause bacte- lus, an irregular level within the ventricle is highly sug-
rial meningitis are Neisseria meningitides and Haemophi- gestive of pus. Venous thromboses can lead to infarction
lus influenzae. S. pneumoniae and N. meningitidis remain with an accompanying hemorrhagic component. Due
the most common causes of bacterial meningitis in to the infection of small arteries and veins on the surface
children. In neonates, group B streptococcus is the most of the brain, extraaxial fluid collections can occur.
common pathogen associated with meningitis, and Lis-
teria monocytogenes also causes disease. Physical exami- When to Suspect Pyogenic Meningitis
nation alone is not sufficient to accurately diagnose or Imaging findings of
rule out meningitis, and lumbar puncture results must High signal intensity of the subarachnoid spaces on
be interpreted with care when attempting to differenti- FLAIR MRI
ate viral from bacterial disease. The classic triad of fever, Meningeal enhancement on postcontrast CT or
neck stiffness, and a change in mental status is present T1-weighted MRI
in less than 50% of cases; however, 95% of patients will Obstructive hydrocephalus
present with at least two of the four symptoms of head- Subdural or epidural fluid collections
ache, fever, neck stiffness, and altered mental status. Complications (infarcts, venous thrombosis, pyo-
Despite the fears of herniation several or many hours cephalus)
after lumbar puncture, cerebrospinal fluid (CSF) analy-
sis is necessary for the specific diagnosis in a majority Subdural Empyema
of the cases. Computed tomographic (CT) scanning of
the head is recommended before lumbar puncture for Extraaxial collections can be sterile fluids (effusions) or
patients with high-risk factors, such as new-onset sei- infected purulent fluids (empyema). Subdural empy-
zures, immunocompromised status, papilledema, focal emas are infected CSF collections between the dura and

361
362 Section III  Problem Solving: Disease Categories

A B

C D
Figure 9-1 Meningitis in a 5-year old child who has suffered from anemia (since her second year of life) and multiple infections. A, B: On axial
fluid-attenuated inversion recovery images, all subarachnoid spaces have high signal intensity (including the basal cistern). Note dilatation of
the temporal horns with a normal-sized fourth ventricle, indicating obstructive hydrocephalus due to the infectious exudates in the basal cistern.
C, D: Meningeal enhancement is observed on postcontrast T1-weighted images are consistent with meningitis.

arachnoid membranes (subdural space). Clinical signs imaging (DWI) has proved useful in the differentia-
include fever, vomiting, meningeal signs, and focal tion between infected collections (empyemas) that are
neurologic signs (e.g., hemiparesis). Bridging veins can bright, with low apparent diffusion coefficient (ADC)
become infected from infected meninges, hematogenous values, and subdural CSF effusions, which have low sig-
spread may occur, and direct extension of infection from nal and ADC values similar to CSF (Figure 9-2).
adjacent structures will lead to infection of the super-
ficial veins. On CT, subdural empyemas are isodense When to Suspect Subdural Empyema
to hypodense extraaxial collections with rim enhance- Patients with meningitis, sinus infection, or ear infec-
ment. MRI has a higher sensitivity for detection of small tion
subdural fluid collections and should be performed Imaging findings:
when subdural collection is suspected. On MRI, subdu- High signal intensity of subdural space on FLAIR MRI
ral empyemas are isointense to the brain parenchyma Rim enhancement on postcontrast images
on T1-WI (increased protein content) and hyperintense High signal of subdural collection on DWI (restricted
on T2-weighted imaging (T2-WI). Diffusion-weighted diffusion)
 Chapter 9 Infection/Inflammation 363

SECTION III
A B

C D
Figure 9-2 Bilateral subdural empyemas in a patient after a tooth implantation procedure. A: Bilateral, high signal intensity, extraaxial collec-
tions are observed on axial fluid-attenuated inversion recovery in the frontal region. Subarachnoid spaces have high signal intensity indicative of
meningeal disease. B, C: On trace diffusion-weighted imaging, subdural fluid collections have high signal with low apparent diffusion coefficient
values (C) representing restricted diffusion due to high viscosity pus in the subdural space. D: On coronal postcontrast T1-weighted magnetic
resonance image, rim enhancement of the subdural empyemas is demonstrated. Note enhancement and signal intensity changes in the left maxil-
lary sinus and left ethmoid cells (source of infection with contiguous spread to meninges and subdural space).

Epidural Empyema Tuberculous Meningitis

Epidural abscesses are the result of contiguous spread of The increased incidence of tuberculosis is clearly
infection from mastoids or paranasal sinuses. The infec- related to the incidence of AIDS, which is considered
tion is located in the epidural space (between the dura the main risk factor for the development of tuberculo-
and the overlying bone). Patients present with fever, sis. Tuberculous infection of the CNS starts as tuber-
mental status changes, and neck pain. On CT, epidural culous meningitis (TBM), with a thick gelatinous
abscess appears as a hypodense epidural mass of lenti- exudate with a predilection for the meninges cover-
form configuration with midline shift and compression ing the base of the brain. Occlusions of the vessels
of the brain parenchyma. On MRI, epidural abscesses that course through the subarachnoid space result in
have iso-signal on T1-WI and high signal on T2-WI, with infarction, most commonly in the region of the basal
enhancement of the thickened dural surface. Epidural ganglia. Communicating-type hydrocephalus is the
abscesses will have restricted diffusion with high signal most common complication in meningeal tuberculo-
on trace DWI and low ADC values. sis. Hydrocephalus will be seen in 51% of patients with
364 Section III  Problem Solving: Disease Categories

A B

C
Figure 9-3 Proven tuberculous meningitis in an HIV-positive patient. A: Hyperintensity of the subarachnoid spaces is demonstrated on axial
fluid-attenuated inversion recovery magnetic resonance image. Bilateral, frontal subdural fluid collections also are seen. B: After gadolinium injec-
tion, meningeal enhancement in the region of the vermis cerebelli is clearly depicted on postcontrast T1-weighted imaging (T1-WI) with magne-
tization transfer contrast (MTC). C: On postcontrast T1-WI without MTC, no meningeal enhancement can be detected.

AIDS-related CNS tuberculosis. Meningeal enhance- show that 56.7% of patients with TBM have infarcts.
ment on en­hanced CT in the basal cisterns and over Hydrocephalus occurs in about one third of patients
the convexity of the brain can be seen in approximately with CNS tuberculosis. The majority of patients have
36% to 61% of TBM cases. Associated tuberculosis epen- large fourth ventricles with adhesive obstructions in
dymitis can be recognized on postcontrast CT scans as the basal cisterns (Figure 9-4).
abnormal enhancement of the ventricular ependyma.
A high prevalence of miliary nodules with a predomi- When to Suspect TBM
nantly leptomeningeal distribution will be seen in the Patients in endemic areas, immunosuppressed patients,
CNS of children with TBM. The most common loca- human immunodeficiency virus (HIV)-positive patients
tions of leptomeningeal nodules are between the cer- Imaging findings:
ebellar folia (86%) and in the region of the vermis and Meningeal enhancement (basal regions of the brain)
quadrigeminal cistern (86%) (Figure 9-3). Children Infarcts (most commonly in the basal ganglia region),
with miliary tuberculosis and TBM usually are younger best depicted with DWI
than those with TBM only. Arteries that course through Obstructive hydrocephalus
the exudate in the basal cisterns become involved, with Enhancement of the cranial nerves
spasm and infarction as a consequence (Figure 9-4). Miliary pattern of meningeal enhancement in small
Studies using DWI and conventional MRI sequences children
 Chapter 9 Infection/Inflammation 365

SECTION III
A B

C D
Figure 9-4 Tuberculous meningitis in a 3-year-old child who presented with impairment of consciousness. Computed tomographic scan of the
brain showed hydrocephalus. On subsequent magnetic resonance imaging of the brain, meningeal enhancement, hydrocephalus, and bilateral
infarcts were detected. A: Marked meningeal enhancement is clearly seen on postcontrast T1-weighted imaging (T1-WI) in the axial plane. Note
dilatation of the temporal horns as a sign of hydrocephalus. B: On axial trace diffusion-weighted imaging, high signal intensity lesions are dem-
onstrated in the basal ganglia region on both sides as well as in the right occipital cortex. C: The lesions have low apparent diffusion coefficients
indicating restricted diffusion in ischemic lesions. D: On T1-WI with fat suppression, enhancement of the subacute ischemic lesion is seen.
366 Section III  Problem Solving: Disease Categories

Cryptococcal Meningitis Table 9-1 

Cryptococcus neoformans is an opportunistic fungus that typ- A. Causative Agents of Acute Viral Encephalitis
ically affects HIV-positive and other patients with compro- 1. Herpes viruses
mised immune systems. Infection of the CNS is a result of Herpes simplex virus types 1 and 2, varicella-zoster virus,
an acquired infection, with hematogenous dissemination Epstein-Barr virus, cytomegalovirus, human herpes virus types
of the infection from the lung to the CNS. Immunocom- 6 and 7
2. Enteroviruses
promised patients may present with headache, nausea, Coxsackie viruses, echoviruses, enteroviruses 70 and 71, pare-
vomiting, altered mental status, personality changes, con- chovirus, poliovirus
fusion, lethargy, obtundation, or even coma. However, 3. Paramyxoviruses
patients may also present with minimal or nonspecific Measles virus, mumps virus
symptoms. Symptoms suspicious for infection, such as 4. Other
Influenza viruses, adenovirus, parvovirus, lymphocytic chorio-
fever and nuchal rigidity, are characteristically absent. meningitis virus, rubella virus
The most common form of cryptococcal CNS infection
B. Causative Agents of Acute Viral Encephalitis (Geographically
is cryptococcal meningitis. Pathologically, subarachnoid Related)
spaces are thickened and filled with multiple organisms
and capsular material. Dilatation of the Virchow-Robin 1. The Americas
West Nile, La Cross, St. Louis, Rocio, Powassan encephalitis,
spaces is a result of the extension of fungus along the Vir- Venezuelan, eastern and western equine encephalitis, Colorado
chow-Robin perivascular spaces into the basal ganglia, tick fever virus, dengue, rabies
thalami, midbrain, and cerebellum. The Virchow-Robin 2. Europe/Middle East
spaces become dilated. With disease progression, dilated Tick-borne encephalitis, West Nile, Tosana, rabies
3. Africa
perivascular spaces become confluent and cystic lesions West Nile (Rift Valley fever virus, Crimean-Congo hemorrhagic
develop called gelatinous pseudocysts or soap bubbles. These fever, dengue, chikungunya), rabies
types of lesions do not have a capsule, and they con- 4. Asia
tain mucinous material and fungal organisms. Crypto- Japanese encephalitis, West Nile, dengue, Murray Valley
coccoma is the only parenchymal form of cryptococcal encephalitis, rabies
5. Australasia
CNS infection. The lesions result from the direct inva- Murray Valley encephalitis, Japanese encephalitis
sion of the brain by the fungus, with the development
of a granulomatous reaction. In cases of cryptococcal­ Modified from Solomon T, Whitley RJ. Arthropod-borne viral encephalitides.
In: Scheld M, Whitley RJ, Marra C, eds. Infections of the central nervous system.
meningitis, enhanced T1-weighted MRI may demon- 2nd ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2004.
strate meningeal enhancement, which usually is nodu-
lar. Dilated Virchow-Robin spaces will be recognized on
MRI as multiple, bilateral, small round- or oval-shaped neurologic signs. In encephalitis, the CSF opening pres-
lesions, usually located in the basal ganglia, which show sure often is slightly raised, and there is usually a mild to
high signal on T2-WI and have a signal slightly higher moderate CSF pleocytosis of 5 to 1,000 cells/mm3. An
than the CSF on T1-weighted MRI. Gelatinous pseudo- electroencephalogram usually shows nonspecific, dif-
cysts are slightly bigger in size and do not differ in mor- fuse, high-amplitude slow waves of encephalopathy, but
phology from the dilated Virchow-Robin spaces on MRI. it is useful to look for subtle epileptic seizures.
The most common locations of gelatinous pseudocysts
are the basal ganglia and the dentate nucleus. Enhance- Herpes Simplex Virus Encephalitis
ment and mass effect will not be present.
Herpes simplex virus type 1 (HSV-1) is the most com-
When to Suspect Cryptococcal Meningitis mon cause of viral encephalitis in adults. Untreated
HIV-positive patients (especially those with a high viral herpes simplex virus encephalitis (HSVE-1) has a high
load level) mortality rate, and the prognosis is dependent on early
Imaging findings: recognition. Pathologically, hemorrhagic encephalitis
Meningeal enhancement (nodular appearance) begins in the inferior and medial temporal lobes and
Dilated Virchow-Robin spaces (basal ganglia) spreads to the frontal lobes in the insular region.
Cystic lesions without enhancement and mass effect Petechial hemorrhages are present in almost every
(signal slightly higher than CSF) representing gelat- case at histopathology. The diagnosis can be confirmed
inous pseudocysts by CSF polymerase chain reaction, with sensitivity
greater than 95% and specificity approaching 100%.
Approximately 3 to 5 days after onset of symptoms,
ENCEPHALITIS
an area of low attenuation in the temporal lobe may be
Viral agents that can cause encephalitis are listed in Table detected. MRI contributes to early diagnosis, with the
9-1. The most common viruses that can cause encepha- earliest imaging findings apparent on FLAIR images 48
litis are the herpes family viruses (HIV, cytomegalovirus hours after onset of symptoms (Figure 9-5). High sig-
[CMV], herpes-zoster virus). The classic presentation of nal intensity lesions will be observed on T2-WI, with
viral encephalitis is generally characterized by an acute low signal on T1-WI. In the acute phase, the enhance-
flu-like prodrome that develops into an illness with high ment usually is not present, and gyriform enhancement
fever, severe headache, nausea, vomiting, and altered on enhanced T1-WI will be observed with disease pro-
consciousness, often associated with seizures and focal gression (Figures 9-5 and 9-6). On DWI, two distinct
 Chapter 9 Infection/Inflammation 367

SECTION III
A B C
Figure 9-5 Herpes simplex virus encephalitis (HSVE-1) in a patient who presented with seizures and consciousness impairment. A, B: Axial
fluid-attenuated inversion recovery image showing high signal intensity in the right insular cortex, cingulated gyrus, and right hippocampal
region. C: No enhancement is observed on postcontrast T1-weighted magnetic resonance image.

types of findings are described in HSVE: lesions ­similar white matter. Two distinct MRI patterns on T2-WI are
to ­cytotoxic edema, and lesions similar to vasogenic observed: (1) diffuse, bilateral, and symmetric high sig-
edema. In the early stage, the majority of HSV-1 enceph- nal intensity involvement of the white matter (butterfly-
alitis cases will have restricted diffusion with high signal like); and (2) bilateral, scattering high signal intensity
(Figure 9-6). DTI analysis has shown slightly reduced lesions in the white and gray matter (patchy) (Figure
mean diffusivity and increased fractional anisotropy 9-7). On T1-weighted MR sequences, the lesions are
values in the earliest phase of HSVE. isointense or slightly hypointense to the white matter.
Enhancement and mass effect are not present. Data
When to Suspect HSVE from recent studies suggest that proton 1H-magnetic
Seizures, impaired consciousness resonance spectroscopy (MRS) could potentially be
Imaging findings: more sensitive than MRI in detecting early CNS involve-
Acute stage: Hyperintensity in the temporal lobe on ment in HIV. Decreased N-acetylaspartate (NAA) level
FLAIR images (unilateral or bilateral), nonenhanc- and elevated choline (Cho) and myoinositol (MI) levels
ing, restricted diffusion (high signal on DWI), measured in the basal ganglia region have been observed
swollen hypointense cortex on T1-WI in patients with HAD (lower NAA/Cr ratio, increased
Subacute stage: Hyperintensity on T2-WI and FLAIR Cho/Cr ratio, increased MI/Cr ratio). Potent antiretro-
with peripheral gyriform enhancement viral combination therapy (highly active antiretroviral
Signs of hemorrhage therapy [HAART]) in patients with HAD may result in
stabilization/regression of white matter abnormalities.
Human Immunodeficiency Virus First follow-up MR examination will reveal a progres-
sion of white matter changes as a result of postinflam-
HIV enters the CNS soon after exposure and resides matory reactions due to immune reconstitutive effects
primarily in microglia and macrophages. Pathologic after the initiation of HAART.
correlates of HIV-related injury include multinucleated
giant cell encephalitis and progressive diffuse leukoen- When to Suspect HIV Infection of the CNS
cephalopathy. Clinically, patients present with demen- HIV-positive patients (especially those with a high viral
tia, designated as HIV-associated dementia (HAD). load level)
The most common reported imaging finding in HIV Imaging findings:
encephalitis is cerebral atrophy, which is seen in 85% of Nonenhancing, bilateral hyperintensities of the white
symptomatic patients. Cortical atrophy is relatively spe- matter (pons, cerebellum, and basal ganglia might
cific to patients with neuropsychological impairment. be involved)
Enlargement of the ventricular system may be seen in Diffuse atrophy
some patients, with or without cortical atrophy. White Patchy, high signal intensity white matter lesions
matter lesions are the second most common MRI find- without enhancement and mass effect
ing in patients with HAD, with an average frequency of Increased MI/Cr ratio on MRS measured in the basal
78%. These lesions have been described in the supra- ganglia
tentorial but also the infratentorial locations, with high Initial progression of SI abnormalities after initiation
signal intensity abnormalities in the pons and cerebellar of HAART; regression with time
368 Section III  Problem Solving: Disease Categories

A B

C D
Figure 9-6 A 43-year-old male patient with severe herpes simplex virus encephalitis (HSVE-1). A: Axial nonenhanced computed tomographic
scan showing bilateral hypodensity of the insular and frontal cortex. B, C: Axial fluid-attenuated inversion recovery magnetic resonance images
demonstrating extensive high signal intensity changes in the insular region, frontobasal region, and both temporal lobes. D, E: On trace diffusion-
weighted imaging (D), high signal with low apparent diffusion coefficient values (E) is observed in the involved cortex, indicating cytotoxic
edema.
Continued
 Chapter 9 Infection/Inflammation 369

SECTION III
E F

G H
Figure 9-6, cont’d F: On susceptibility-weighted imaging, punctuate low signal intensity changes are shown in the affected regions, represent-
ing a hemorrhagic component. G: On postcontrast T1-weighted imaging (T1-WI), no enhancement is observed (acute stage). H: On follow-up
magnetic resonance examination 10 days later (subacute stage), gyriform enhancement can be demonstrated on coronal enhanced T1-WI.
370 Section III  Problem Solving: Disease Categories

infection are retinitis, myelitis/polyradiculopathy, diffuse

micronodular encephalitis, ventriculoencephalitis, and
mononeuritis multiplex. In CMV diffuse micronodular
encephalitis, small microglial nodules and inclusion-
bearing cytomegalic cells are widely distributed in the cor-
tex, basal ganglia, brainstem, and cerebellum. The most
common imaging findings in patients with CMV enceph-
alitis are cortical atrophy, periventricular enhancement,
and diffuse white matter abnormalities. Generalized
atrophy is the most commonly reported CT abnormality.
In ventriculoencephalitis, periventricular enhancement
has been described. The presence of thin linear enhance-
ment suggests a viral etiology (CMV or varicella-zoster
virus), whereas the presence of nodular enhancement
suggests a diagnosis of primary CNS lymphoma. In an
AIDS patient, a case of cerebral mass lesion due to CMV
has been reported. In immunocompromised patients,
CMV-induced cerebellitis can occur with swollen cerebel-
lar cortex and linear enhancement (Figure 9-8).

When to Suspect CMV Infection of the CNS

HIV-positive patients, patients after BMT or organ trans-
Figure 9-7 Human immunodeficiency virus (HIV) encephalopathy plantation
in a 39-year-old male HIV-positive patient who presented with signs Imaging findings:
of subcortical dementia. Cerebrospinal fluid analysis revealed high Generalized atrophy
viral load level. Axial fluid-attenuated inversion recovery magnetic White matter lesions
resonance image showing bilateral, nonenhancing (not shown), high
signal intensity abnormalities in the frontal white matter. Subcortical Periventricular enhancement
fibers are not involved. Note enlargement of the ventricles and sub-
arachnoid spaces in HIV-associated diffuse atrophy.
Progressive Multifocal
Leukoencephalopathy
Cytomegalovirus
Progressive multifocal leukoencephalopathy (PML) is
CMV belongs to the family of herpes viruses. In adults, an opportunistic infection caused by the JC Polyomavirus.
the infection is the result of reactivation of a latent infec- The incidence of PML ranges between 0.7% and 11% in
tion. Five distinct neurologic syndromes related to CMV the HIV population. Histopathologic features of PML

A B
Figure 9-8 Acute viral cerebellitis in an immunocompromised patient 2 months after liver transplantation who presented with nystagmus,
dysarthria, and vertigo. Cytomegalovirus was suspected to be the causing agent. A: Coronal T2-weighted magnetic resonance image showing
diffuse increased signal intensity involving both cerebellar hemispheres. B: On coronal enhanced T1-weighted magnetic resonance image, faint
enhancement is observed only in the left cerebellar hemisphere.
 Chapter 9 Infection/Inflammation 371

SECTION III
AS

A B C

D E F

Figure 9-9 Cerebrospinal fluid–proven progressive multifocal leukoencephalopathy (PML) in a 42-year-old male HIV-positive patient. A: On
nonenhanced computed tomographic scan of the brain, a hypodense area is observed in the right temporal region. Mass effect is not present. B:
On fluid-attenuated inversion recovery magnetic resonance (MR) image in the axial plane, the scalloped lesion is hyperintense with no mass effect
on the right occipital horn. C, D: Marked hypointensity is demonstrated on T1-weighted MR image (C) with no enhancement on postcontrast
T1-weighted image (D). E, F: On trace diffusion-weighted imaging, PML lesion has low signal with peripheral high signal outlining the lesion (E).
Corresponding apparent diffusion coefficient (ADC) values can be measured on the ADC map (F), indicating higher diffusivity in the demyelinat-
ing part of the lesion and restricted diffusion on the border of the lesion where the advancing edge of the lesion occurs.

include demyelination with enlarged oligodendroglial effect is mild or absent. Lesions have been reported in the
nuclei and bizarre astrocytes. Patients present with any supratentorial and infratentorial locations. On MRS, PML
combination of weakness, speech disturbances, limb lesions have significantly reduced NAA, lactate presence,
uncoordination, cognitive deficits, or visual impairment. and increased choline and lipids. Without treatment, the
The disease presents usually with multifocal white mat- prognosis for PML usually is poor. A more benign clini-
ter lesions that occur in any location in the white matter. cal course has been reported in only a small number of
On CT scans, PML lesions are recognized as patchy, scal- patients. Recent studies have shown clinical and radio-
loped, low-density lesions located in the white matter. logic improvement in patients with PML who underwent
PML lesions are patchy, scalloped, hyperintense lesions potent antiretroviral therapy regimens. On DWI, PML
on T2-weighted MRI, located in the white matter, with lesions are characterized by a central core of low signal
finger-like extension along the white fibers (Figure 9-9). intensity (increased diffusivity) surrounded by a rim of
The lesions have marked low signal on T1-weighted MRI signal hyperintensity (restricted diffusivity) (Figure 9-9).
and show only rarely peripheral, faint enhancement (Fig- Restricted diffusion has been identified as a characteristic
ure 9-9). Subcortical fibers usually are involved, and mass finding in phases of rapid progression in PML.
372 Section III  Problem Solving: Disease Categories

A B

C D
Figure 9-10 Listeria brainstem encephalitis in a 60-year-old patient. A–C: On axial fluid-attenuated inversion recovery images, high signal
intensity abnormalities are seen in the pons, midbrain, and thalamus on both sides. Slightly increased intensity is noted in both hippocampal
regions. Pons is not enlarged. D: No enhancement is observed on enhanced T1-weighted magnetic resonance image in the axial plane.

When to Suspect PML Infection of the CNS Brainstem Encephalitis

HIV-positive patients; rarely, patients after BMT or organ
(Mesenrhombencephalitis)
transplantation
Imaging findings: Mesenrhombencephalitis is a form of brainstem inflam-
Multifocal high signal intensity white matter lesions mation predominantly involving the deep and vital
on T2-WI portions of the brain (mesencephalon and rhomb-
Involvement of subcortical arcuate fibers encephalon). Suggestive clinical features of brain-
No enhancement (rarely faint peripheral enhance- stem encephalitis are lower cranial nerve involvement,
ment) myoclonus, autonomic dysfunction, or even locked-in
No mass effect syndrome. The cause is rarely detected, but potentially
Fast progression on follow-up images causative agents are enteroviruses (especially EV71), fla-
Enhancement after initiation of HAART (responders) viviruses, Listeria, M. tuberculosis, Brucella, and Borrelia.
Elevated diffusivity (low signal on DWI and high L. monocytogenes and HSV are two known causes of mesen-
ADC), with restricted diffusivity of the lesion bor- rhombencephalitis that must be treated early to prevent
ders (high signal on DWI with low ADC values) devastating consequences. On MRI, patchy areas of T2
 Chapter 9 Infection/Inflammation 373

SECTION III
A B

C D
Figure 9-11 Cerebritis and pyocephalus in a 30-year-old patient. A: Axial fluid-attenuated inversion recovery image showing large area of
high signal intensity in the right temporal lobe. B: No enhancement is seen on axial postcontrast T1-weighted magnetic resonance image. C: On
diffusion-weighted imaging, marked hyperintensity was seen with additional high signal in both occipital horns. D: Low apparent diffusion coef-
ficient (ADC) value on an ADC map in the temporal region suggests restricted diffusion in an area of cerebritis. Signal changes in the occipital
horns suggest pyocephalus with intraventricular purulent fluid.

signal hyperintensity usually are scattered throughout sinuses, middle ear, or the mastoid air cells is the most
the affected brainstem regions. Brainstem swelling will common source of brain abscess. Approximately 10%
be present in only 30% of the cases. Contrast enhance- of all abscesses will be seen after trauma, and in 25%
ment usually will not be present (Figure 9-10). A pattern of patients brain abscess is the result of hematogenous
of patchy enhancement has been described in cases of dissemination. Otogenic and dental source abscesses
L. monocytogenes infections. usually are caused by anaerobic organisms (Streptococ-
cus and Bacteroides spp). Staphylococcus aureus is the most
commonly identified organism after trauma. Fungal
BRAIN ABSCESS
brain abscesses are most commonly caused by Aspergil-
Brain abscess is a life-threatening condition. Approxi- lus spp, which usually is detected in severely immuno-
mately 2,500 cases are reported annually in the United compromised patients. Toxoplasma gondii abscesses are
States. Contiguous spread of infection from the ­paranasal common in patients with AIDS.
374 Section III  Problem Solving: Disease Categories

Most brain abscesses are the result of a single organ- enhancement. However, the target sign on CT can also
ism, although 30% to 60% of infections are polymi- be seen in other infectious processes. The MRI character-
crobial. istics of intracranial tuberculoma are extremely diverse.
An isointense or hypointense core with a hyperintense
Pyogenic Brain Abscess rim on T2-weighted and FLAIR images is the most com-
mon presentation (Figure 9-14).
Evolution of an abscess in the brain occurs in four Three histologic types of tuberculous granulo-
stages: (1) early cerebritis stage, characterized by a mas with corresponding radiologic findings on MRI
poorly demarcated area of brain softening with vas- have been described: (1) noncaseating granuloma (T1
cular congestion, petechial hemorrhage, and edema; hypointense, T2 hyperintense, nodular enhancement);
(2) late cerebritis stage; (3) early capsule formation stage; (2) caseating granuloma with a solid center (T1 isoin-
and (4) late capsule formation stage, with a collagenous tense/hypointense, T2 isointense/hypointense, rim
capsule. In the late cerebritis stage, low attenuation will enhancement); and (3) caseating granuloma with a
be recognized on CT scans, with gyral enhancement. On liquid center (T1 hypoin­tense, T2 hyperintense, rim
precontrast CT images, formed abscesses may show a enhancement).
smooth, complete capsular ring, which enhances with Tuberculomas will have a nonspecific appearance on
contrast in a ring-like fashion. Perifocal hypodense DWI, with ADC values ranging from 0.406 to 2.64 × 10−3
edema is always present. On MRI, a hyperintense, ill- mm2/s (Figure 9-14). Lesions with hyperintense centers
defined area will be seen on T2-weighted MRI, without on T2-WI are likely to have increased signal on DWI,
enhancement (Figure 9-11). In the later stage, peripheral whereas those with hypointense centers on T2-WI will
enhancement might be seen. have decreased signal intensity on DWI. DWI and MRS
MRI findings of brain abscess will depend on the may help to determine the nature of cerebral tubercular
abscess stage. In the early cerebritis stage, a poorly lesions; however, they do not help in specific character-
demarcated area of high signal intensity will be seen on ization. On MRS, lipids will be present in approximately
T2-weighted MRI. During the late cerebritis and abscess 86% of cerebral tuberculomas. Calcification might be
stages, a thin-walled hypointense ring representing a seen in old tuberculous abscesses.
capsule will be recognized on T2-WI. A mature abscess
has a well-defined ring with marked perifocal edema When to Suspect Tuberculoma
and mass effect delineated on postcontrast images Patients in endemic areas, HIV-positive patients, immu-
­(Figure 9-12). nosuppressed patients
Untreated pyogenic brain abscesses have a charac- Imaging findings:
teristic appearance on DWI, demonstrating a central Ring-enhancing masses with mass effect and perifocal
­hyperintensity on trace images and low ADC (Figure edema
9-13). Restricted diffusion in abscesses has been attrib- Various signal on T2-WI (depending on stage)
uted to the high viscosity of pus due to the presence of Various signal on DWI
inflammatory cells, bacteria, and macromolecules. Lipid peak on MRS
Additional findings that suggest tuberculous infec-
When to Suspect Pyogenic Brain Abscess tion of the CNS (meningitis with hydrocephalus,
Young male adult infarcts in basal ganglia region, involvement of cra-
Imaging findings: nial nerves)
Intracerebral (intraaxial) mass lesion with smooth Healed tuberculoma may calcify
ring-like enhancement
High signal intensity center on T2-WI Aspergillus Brain Abscess
Marked perifocal edema and mass effect
Homogenously high signal on DWI with low ADC Aspergillus abscesses account for 18% to 28% of all
values (restricted diffusion) fungal brain abscesses and are the most common CNS
Amino acids (succinate, pyruvate, alanine) and lipid complication occurring after BMT. Meningitis, abscess
peaks on MRS or granuloma, vascular invasion with thrombosis and
infarction, and hemorrhage and aneurysm formation
Tuberculosis are manifestations of cerebral aspergillosis. Pathologi-
cally, hyphal elements invade cerebral vessels, result-
Tuberculomas, tuberculous abscesses, and focal tuber- ing in thrombosis and infarctions. Sterile infarctions
culous cerebritis are parenchymal forms of CNS tuber- become septic when the fungus erodes the wall of the
culosis. In focal tuberculous cerebritis, intense gyral vessel, with extension into the brain parenchyma with
enhancement will be seen on postcontrast CT scans. inflammatory reactions and necrosis. The incidence of
Tuberculomas may be solitary or multiple. They can aspergillosis in patients after BMT who present with
be located anywhere in the brain but predominantly stroke is reported to be 25%.
in the supratentorial compartment. On CT, mature The most common findings in cerebral aspergillosis
granulomas are ring-enhancing lesions. The “target are multiple T2-WI homogeneous hyperintense lesions
sign” has also been described in CNS tuberculoma, smaller than 1 cm and central hypointensity with sur-
representing central calcification or punctate enhance- rounding hyperintensity in lesions larger than 1 cm.
ment surrounded by a zone of hypodensity and a rim of On MRI, intracerebral lesions in aspergillosis usually
 Chapter 9 Infection/Inflammation 375

SECTION III
A B C

D E
Figure 9-12 Cerebellar brain abscess in a 3-year-old child. The abscess was surgically drained, but no definite organism could be isolated.
A: Axial fluid-attenuated inversion recovery magnetic resonance image showing intermediate signal intensity mass in the right cerebellar
­hemisphere, with perifocal edema and mass effect. B: The lesion has low signal intensity rim on coronal T2-weighted image, representing an
abscess capsule. C, D: On trace diffusion-weighted imaging (C), the abscess has high signal, with low apparent diffusion coefficient (ADC) on the
ADC map (D). E: Smooth enhancement of the abscess capsule is seen on postcontrast T1-weighted imaging.
376 Section III  Problem Solving: Disease Categories

A B

C
Figure 9-13 Bacterial brain abscess in the left frontal lobe of a 40-year-old female patient who had a stereotactic biopsy of a lesion 2 months
before the onset of headache, hallucinations, nausea, and gait disturbances. A: On gadolinium-enhanced, T1-weighted axial magnetic resonance
image, ring-like enhancing lesion is seen in the left frontal lobe with mass effect and surrounding edema. B: Abscess formation has marked high
signal on trace diffusion-weighted imaging. C: On apparent diffusion coefficient (ADC) map, low ADC values can be measured in the abscess
cavity due to restricted diffusion.
 Chapter 9 Infection/Inflammation 377

SECTION III
A B C

D E F
Figure 9-14 Central nervous system tuberculosis in a 5-year-old child with multiple tuberculomas and hydrocephalus. A: Multiple low signal
intensity lesions with sharp margins are seen in the posterior fossa on axial fluid-attenuated inversion recovery image. B: On coronal T2-weighted
image, the lesions show marked hypointensity and subsequent hydrocephalus. C: On axial T1-weighted image, the lesions are slightly hyperintense.
D: Marked widening of the ventricles is present due to obstruction of the fourth ventricle. E: Ring-enhancing lesions demonstrated on gadolinium-
enhanced T1-weighted image represent multiple tuberculomas. F: Smaller ring-enhancing tuberculomas are present in the frontal and occipital lobes.
378 Section III  Problem Solving: Disease Categories

A B
Figure 9-15 Proven cerebral aspergillosis in a patient with acute myelocytic leukemia (A, B). Multiple ring-like or nodular enhancing lesions
are seen on postcontrast T1-weighted magnetic resonance images.

have low signal centrally or peripherally on T2-WI,

Cryptococcoma
probably due to accumulation of fungi containing
iron, magnesium, and manganese, as well as blood Cryptococcomas usually are seen in immunocompro-
breakdown products (Figure 9-15). However, low sig- mised individuals (Figure 9-18). However, isolated
nal on T2-WI is not specific for aspergillosis; it may be cryptococcomas of the CNS have also been described
seen in various infections (tuberculoma) as well as in in immunocompetent adults, as occurs in the presence
neoplastic brain lesions. Contrast enhancement usu- of underlying sarcoidosis. Imaging characteristics of
ally is missing and is seen only in patients with rela- cryptococcomas can overlap with those of tumors and
tively preserved immune status. On DWI, aspergillus abscesses of other origin. Cryptococcomas are hypodense
abscesses might be bright with low ADC values, indi- on CT with high signal on T2-WI and low signal on
cating restricted diffusivity, and are indistinguishable T1-weighted MRI. On enhanced images, the lesions usu-
from bacterial abscesses (Figure 9-16). ADC values ally demonstrate a ring-like or nodular enhancement
measured in bacterial abscesses usually are lower than and cannot be distinguished from granulomas of other
those measured in fungal lesions. This may be due origin. They occur most commonly in the cerebellum,
to the lower cell density in fungal abscesses and, to brainstem, basal ganglia, and ­temporoparietal regions.
a lesser extent, to the presence of hemorrhage. Some Hypointensity on diffusion-weighted MRI scans, with
have low signal with high ADC values and can mimic elevated ADC, has been reported in one case.
necrotic neoplasms.
Fungal abscesses may also present as microabscesses, When to Suspect Cryptococcoma
which are seen more frequently in candida infection HIV-positive patients, patients with sarcoidosis
(Figure 9-17). Imaging findings:
Ring-enhancing masses with mass effect and perifocal
When to Suspect Aspergillus Brain Abscess edema
Patients after BMT or organ transplantation, HIV-­ Low signal on DWI (high ADC values)
positive patients In combination with gelatinous pseudocysts or
Imaging findings: dilated Virchow-Robin spaces
Ring-enhancing masses with mass effect and perifocal
edema in an immunocompetent patient
Toxoplasmosis
Nonenhancing lesions in an immunocompromised
patient Cerebral toxoplasmosis results from infection by the
High signal on T1-WI or low signal on susceptibility- intracellular protozoan T. gondii. After acute infection,
weighted imaging, indicating hemorrhage the latent form, called encysted bradyzoites, remains
Cortical location in the tissues until a decline in immunity. Rupture of
Low signal on T2-weighted MRI the cysts releases the free tachyzoite, which causes
High or intermediate signal on DWI acute illness. In AIDS patients, Toxoplasma causes
 SECTION III
A B C

D E
Figure 9-16 Cerebral aspergillosis in 16-year-old girl with acute lymphoblastic leukemia (ALL) who suffered from invasive aspergillosis, with
aspergillus granuloma in the lung and liver. A: On axial fluid-attenuated inversion recovery magnetic resonance (MR) image, hyperintense corti-
cal lesion is detected in the right parietal region. B: The lesion has a ring-like appearance on postcontrast MR images. C, D: On trace diffusion-
weighted imaging (C), a high signal is seen, with a low apparent diffusion coefficient value (D), indicating restricted diffusivity. E: On coronal
T2-weighted MR image, a low signal intensity centrally is observed and may be due to iron, magnesium, manganese, or blood products found in
the aspergillus fungus.

A B
Figure 9-17 Candida brain abscesses in an immunocompromised patient (A, B). Postcontrast T1-weighted magnetic resonance images in the
axial plane showing multiple small abscesses (microabscesses) in the white matter of the frontal lobe.
380 Section III  Problem Solving: Disease Categories

Figure 9-18 Cerebral cryptococcosis in a patient with acquired

immunodeficiency syndrome. Axial enhanced T1-weighted magneti-
zation transfer contrast magnetic resonance image showing nodular
enhancing lesion (cryptococcoma) in the region of the third ventricle,
with slightly enlarged ventricular system.

­ ecrotizing ­encephalitis. Lesions characteristic of toxo-

n thallium-201 (201Tl) brain single-photo emission com-
plasma-induced necrotizing encephalitis have three puted tomography (SPECT) in AIDS patients has proved
well-defined zones: avascular; necrotic center, with an to be helpful in distinguishing toxoplasmosis from
intermediate zone with intense inflammatory reaction; lymphoma. A positive 201TI brain SPECT is suggestive
and peripheral zone with the encystic form of Toxo- of CNS lymphoma, and negative uptake suggests infec-
plasma. On nonenhanced CT scans, Toxoplasma lesions tion (toxoplasmosis) in AIDS patients. The potential
are hypodense, with edema and mass effect. Solid, nod- use of 18F-fluorodeoxyglucose (FDG) positron emission
ular, or ring-enhancing lesions typically are observed on tomography (PET) in differentiating lymphoma from
postcontrast studies. The most common locations are toxoplasmosis in AIDS patients also has been examined.
the basal ganglia and the corticomedullary junction. On The results of the studies have shown that FDG-PET can
T1-weighted MRI, Toxoplasma lesions have isointense to accurately differentiate lymphoma from infections. The
low signal centrally. Signal intensity on T2-WI depends standardized uptake values over cerebral lesions were
on the stage of the lesion, which could be isointense, much higher in lymphomas than in Toxoplasma lesions.
hypointense, or hyperintense (Figure 9-19). Enhanced
T1-WI reveals ring or nodular enhancement. Approxi- When to Suspect CNS Toxoplasmosis
mately 10 days after initiation of therapy, a decrease in HIV-positive patients; patients after BMT or organ trans-
the number and size of the lesions, with a reduction in plantation
edema and mass effect, should be observed on follow- Imaging findings:
up MR examinations. Calcifications are often seen in Single/multiple ring-enhancing lesions
healed foci. Toxoplasmosis shows a wide spectrum of Mass effect and marked perifocal edema
diffusion characteristics, with ADC ratios ranging from Low signal or isotensity on T1-weighted MRI
0.8 to 2.8, which have significant overlap with those No specific pattern on T2-weighted MRI (low/isointe­
of lymphoma (Figure 9-19). The MRS pattern of Toxo- nse/high)
plasma lesions is nonspecific, consistent with anaerobic Hemorrhagic after antitoxoplasma therapy
inflammation within the abscess (Figure 9-19). Based Nonenhancing or primarily hemorrhagic lesions in
on conventional MRI, cerebral toxoplasmosis cannot be patient after BMT
distinguished from primary cerebral lymphoma. Use of Varied appearance on DWI and ADC map
 Chapter 9 Infection/Inflammation 381

SECTION III
A B C

ppm
4 3 2 1
D E F
Figure 9-19 Central nervous system toxoplasmosis in a patient with acquired immunodeficiency syndrome. A: On axial fluid-attenuated
inversion recovery image, cortically located lesion in the left frontal lobe is seen. The lesion has a multilayer (target-like) appearance and marked
perifocal edema. Note small subcortical signal abnormalities in the right frontal lobe. B: On T1-weighted magnetic resonance (MR) image, the
lesions and surrounding edema have low signal. C: On postcontrast T1-weighted MR image, peripheral ring-like enhancement is seen. D, E:
Inhomogeneous signal is observed on trace diffusion-weighted imaging and apparent diffusion coefficient map. F: 1H-Magnetic resonance spec-
troscopy shows low N-acetylaspartate peak, increased choline peak, and large lipid peak.
382 Section III  Problem Solving: Disease Categories

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2003;13:1876-1890. coefficient values in distinguishing central nervous system toxoplasmosis
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1987;75:185-198. cerebral infarction in tuberculous meningitis by diffusion weighted
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1994;162:425-430.
 chapter 10

Metabolic Disorders
Robert J. Young, Sofia S. Haque, and John K. Lyo

INTRODUCTION
typically is seen as hypodense lesions on computed
Metabolic diseases of the brain represent a diverse group tomographic (CT) scan and as T1 hypointense and
of diseases caused by inherited (inborn) and acquired T2 hyperintense lesions on magnetic resonance imag-
(radiation, toxic) errors in metabolism. Many metabolic ing (MRI). These abnormalities may be symmetric or
diseases consist of otherwise heterogeneous groups of
disorders with varied pathophysiologies that interrupt
critical metabolic pathways in different ways but with Table 10-1 Inherited Metabolic Disorders
the common end result of abnormal accumulation or Mitochondrial • Mitochondrial myopathy, encepha-
insufficient production of a critical brain compound. disorders lopathy, ­lactic acidosis, and stroke-
Imaging of metabolic disorders often has high sensi- like episodes (MELAS)
tivity but poor specificity. The end stage of most meta- • Myoclonic epilepsy with ragged red
bolic diseases is diffuse atrophy, enlarged ventricles, and fibers (MERRF)
abnormal white matter. This is true for both the leuko- • Subacute necrotizing encephalomy-
elopathy (Leigh)
dystrophies, which primarily involve the white matter, • Kearns-Sayre syndrome (KSS)
and the poliodystrophies, which primarily involve the • Trichopoliodystrophy (Menkes
gray matter. The greatest potential for differential accu- ­syndrome)
racy and a positive impact on patient therapy lies in early • Progressive cerebral poliodystrophy
imaging of these diseases, when distinctive patterns may (Alpers syndrome)
be identified. Despite frequent limitations in establish- • Neurogenic weakness, ataxia, and
retinitis pigmentosa (NARP)
ing a definite diagnosis, imaging has a critical role in the • Hearing loss, ataxia, myoclonus
triage, diagnosis, prognosis, and management of these (HLAM)
patients. The diseases may be grouped according to the • Leber hereditary optic neuropathy
common biochemical defect (Table 10-1). (LHON)
Although this categorization is accurate, it is imprac- • Mitochondrial myopathy, neuropa-
tical from an imaging approach due to the high vari- thy, and gastrointestinal encephalo-
myopathy (MNGIE)
ability and overlapping abnormalities of many diseases.
In order to provide a practical radiographic framework Lysosomal ­storage • Mucopolysaccharidosis
from which a reasonable differential diagnosis may be ­disorders • GM2 gangliosidosis
formed, this chapter organizes the metabolic disorders • Metachromatic leukodystrophy (MLD)
• Globoid cell leukodystrophy (Krabbe
into groups based on the most distinctive radiologic disease)
abnormality: white matter disease, cortical gray matter
disease, and deep gray matter disease. These are followed Peroxisomal • Zellweger disease
disorders • Adrenoleukodystrophy/
by a discussion of magnetic resonance (MR) diffusion
adrenomyeloneuropathy
and MR spectroscopy. When a disorder displays mul-
tiple manifestations and may fall into more than one Organic acide- • Glutaric acidemia
category, the disorder may be mentioned in different sec- mias and amino • Proprionic acidemia
acidurias • Canavan disease (spongiform
tions with the emphasis on the most characteristic imag-
­degeneration of the brain, von
ing feature(s). As with the rest of this book, the purpose Bogaert-Bertrand disease)
of this chapter is not to provide an extensive review but • Maple syrup urine disease (MSUD)
rather to suggest a systemic approach for radiologic inter- • Urea cycle disorders (UCD)
pretation. The classic or most common manifestations • Methylmalonic acidemia (MMA)
are discussed with the focus on the inherited metabolic • Alexander disease
disorders; the acquired metabolic and toxic metabolic • Phenylketonuria (PKU)
disorders are briefly presented for comparison purposes. Other • van der Knaap leukoencephalopathy
• Neurodegeneration with brain iron
­accumulation (NBIA)/Hallervorden-
PART I: WHITE MATTER DISEASE Spatz syndrome (HSS)
Bilaterally symmetric white matter signal abnormalities • Huntington disease
• Wilson disease
suggest hereditary leukoencephalopathy, the primary
• Pelizaeus-Merzbacher disease
white matter diseases. On imaging, white matter ­disease

383
384 Section III  Problem Solving: Disease Categories

Table 10-2 L
 eukodystrophies Categorized by White
Matter Abnormality

Hypomyelination • Pelizaeus-Merzbacher disease (PMD)

Dysmyelination • Mitochondrial disorders
Delayed myelination • Amino acidurias
Phenylketonuria (PKU)
 Maple syrup urine disease
(MSUD)
Methylmalonic acidemia (MMA)
 Nonketotic hyperglycinemia
(NKH)
 Hydroxymethylglutaryl-coenzyme
A (HMG-CoA) lyase deficiency
• Organic acidopathies
Glutaric acidemia
Proprionic acidemia
Demyelination • Globoid cell leukodystrophy (Krabbe
Primary disease)
Secondary • Metachromatic leukodystrophy
• Adrenoleukodystrophy /
­Adrenomyeloneuropathy
• Cerebrohepatorenal syndrome
­(Zellweger disease)
• Alexander disease
• Lysosomal storage disorders Figure 10-1 Adrenoleukodystrophy. Axial fluid-attenuated inver-
GM2 gangliosidosis sion recovery image showing symmetric regions of hyperintensity in
the peritrigonal white matter, splenium of the corpus callosum, and
Niemann-Pick disease
along the corticospinal tracts in the posterior limbs of the internal
Fabry disease capsules, with typical central and posterior distribution of disease.
• Mucopolysaccharidosis
• Sjoögren-Larsson syndrome
• Cerebrotendinous xanthomatosis i­ ndistinguishable in the late stages due to diffuse sym-
• Canavan disease metric white matter signal abnormalities and volume
Vacuolating ­ • Megaloencephalic loss. Thus, early imaging offers the best possibility for
myelinopathies ­leukoencephalopathy with subcorti- detection of patterns that favor one or a few diagnoses,
cal cysts (van der Knaap syndrome) and imaging is generally suggestive (and aids in narrow-
• Leukoencephalopathy with vanish- ing down clinical and laboratory tests for confirmation)
ing white matter (LVWM)
rather than diagnostic.

g­ eographic, patchy or confluent, and may be associated Central White Matter Disorders
with swelling or volume loss. The wide range of bio-
chemical disturbances includes peroxisomal disorders, Is There Symmetric Peritrigonal Involvement
lysosomal storage disorders, organic acidurias, and ami- Crossing the Posterior Corpus Callosum?
noacidemias. The three main pathophysiologic mecha- X-linked adrenoleukodystrophy is part of a spectrum
nisms affecting myelin are (1) deficient or abnormal of diseases that include adrenomyeloneuropathy and
myelin formation, (2) loss or destruction of previously adrenoleukomyeloneuropathy. Adrenoleukodystrophy
normal myelin, and (3) vacuolation with rarefaction commonly presents with bilateral symmetric low atten-
and replacement of myelin by cerebrospinal fluid (CSF) uation of the peritrigonal white matter and the poste-
(Table 10-2). rior corpus callosum, corticospinal tracts, and optic
The imaging changes reflect increased water content tracts. On MRI, corresponding areas of T2 hyperinten-
within the white matter tracts due to destruction or sity with early sparing of the subcortical U fibers are
malformation of the myelin sheaths around the axons seen (Figure 10-1). Centrifugal disease progression later
running in the white matter or due to edema related to involves the subcortical white matter. Three discrete
abnormal water balance between the white matter and zones of central gliosis, intermediate active demyelin-
the extracellular spaces. A similar appearance can be ation with enhancement, and peripheral leading edge
caused by abnormal cellular infiltration (with or with- of active demyelination without enhancement have
out demyelination and axonal loss) from processes such been described. Administration of steroids may cause
as inflammation due to infection or autoimmune dis- the leading edge of enhancement to disappear. The
ease, gliosis related to chronic insult to the white mat- nonenhancing abnormality peripheral to the enhanc-
ter from radiation, trauma, or medication, or infiltrating ing margins may represent early demyelination that has
neoplasms. not yet developed an inflammatory response. Decreased
Distinguishing the heritable leukoencephalopathies ­fractional anisotropy (FA) and increased mean diffusiv-
from each other is difficult due to the broad overlap ity by diffusion tensor imaging (DTI) may be a more
in the distribution of white matter signal abnormal- sensitive marker for demyelination. The nonenhancing
ity and enhancement characteristics, and they are signal abnormality central to the rim of enhancement
 Chapter 10 Metabolic Disorders 385

SECTION III
Cho

0.10

NAA

0.05
Cr
Cr2

0.00

A B 4 3 2 1 ppm
Figure 10-2 Adrenomyeloneuropathy. A: Fluid-attenuated inversion recovery image showing symmetric regions of hyperintensity in the hemi-
spheric white matter with mild frontal lobe predominance and involvement of the corpus callosum. B: Spectroscopy of the posterior periventricu-
lar white matter reveals decreased N-acetylaspartate and increased choline, which are nonspecific but consistent with the demyelinating diseases.

may represent gliosis and scarring from burned out dis- BOX 10-1 X-Linked Adrenoleukodystrophy
ease. Less frequently, the disease process begins in the ­(Spectrum: Adrenomyeloneuropathy,
frontal lobes and progresses posteriorly to resemble Adrenoleukomyeloneuropathy)
Alexander disease (Figure 10-2 and Box 10-1).
nn X-linked mutations in ABCD1 gene
Is There Focal Involvement of Bilateral nn ABCD1 is a peroxisomal transporter for very long
Caudothalamic Grooves? chain fatty acids, which are degraded within the per-
Zellweger syndrome (cerebrohepatorenal syndrome) oxisome
shows profound diffuse hypomyelination with dif- nn Accumulation of undegraded very long chain fatty
fuse white matter T2 signal hyperintensity and CT acids
low attenuation. Small germinolytic cysts in the cau- nn Both males and females have noninflammatory axo-
dothalamic grooves and subependyma of the lateral nal loss; heterozygotes females are resistant to the
­ventricles are visible on fluid-attenuated inversion inflammatory demyelinating disease
recovery images (also visible by ultrasound) (Figure nn Many clinical forms exist, including those without
10-3). Abnormal signal in the basal ganglia can be seen neurologic involvement, such as Addison disease
related to hyperbilirubinemia from the related liver nn 31%–50%; childhood cerebral adrenoleukodystro-
disease and can confuse the picture. Zellweger syn- phy (CCALD) onset at 3–10 years with ”bronzed”
drome can be distinguished from the other leukodys- skin, behavioral and learning problems, and gait,
trophies by the presence of disorganized cortical gyri, hearing, and vision disturbances, with rapid progres-
pachygyria, and other neuronal migration disorders. sion to dementia and death
Optic nerve atrophy may be seen. Enhancement is not nn 40%–46%; adrenomyeloneuropathy onset at 30 years
typical for Zellweger disease but can be seen with the with a chronic course that does not benefit from bone
related processes of neonatal adrenoleukodystrophy marrow transplantation (as opposed to CCALD)
and infantile Refsum disease. This may be due to the
earlier and more severe course of Zellweger with death
before the inflammatory component becomes appar-
ent (Box 10-2). sparing of the subcortical U fibers. There is also early
sparing of the perivascular white matter, leading to
Is There Symmetric Anterior and Posterior radial stripes of spared white matter extending later-
Distribution? ally from the edges of the lateral ventricles reminiscent
Metachromatic leukodystrophy shows symmetric con- of a “tigroid” appearance on T2-weighted sequences
fluent areas of T2 hyperintensity in the anterior and (a nonspecific finding also noted with Pelizaeus-
posterior periventricular and peritrigonal white mat- Merzbacher disease) (Figure 10-4). Late disease dem-
ter in a confluent butterfly pattern, which may also onstrates widespread white matter T2 hyperintense
involve the cerebellar white matter. There is early demyelination involving both deep and peripheral
386 Section III  Problem Solving: Disease Categories

A B
Figure 10-3 Zellweger syndrome. A, B: Axial T2-weighted images showing microgyria in the right frontal and parietal cortex and left rolandic
cortex (arrows, A). Bilateral symmetrical laminar heterotopia is seen as a thin line of gray matter between the ventricle and the cortex in the frontal
and parietal lobes (arrows, B). (From Huybrechts SJ, Van Veldhoven PP, Hoffman I, et al. Identification of a novel PEX14 mutation in Zellweger
syndrome. J Med Genet 2008;45:376-383.)

commonly involves the splenium and peritrigonal

BOX 10-2 Zellweger Syndrome (Cerebro- white matter. Occasionally, T2 hypointense changes
hepatorenal Syndrome) and Other are seen in the thalamus, posterior limb of the inter-
­Peroxisomal Disorders nal capsule, and cerebellum (Box 10-3).
nn Spectrum of autosomal recessive mutations in one of
Is There Early Predilection for the Posterior
several genes for peroxin proteins necessary for per-
White Matter?
oxisome assembly
Phenylketonuria demonstrates primarily supratentorial
nn Mutation leads to near-complete absence of peroxi-
diffuse white matter T2 hyperintensity involving the
somes within cells
posterior white matter with initial sparing of the sub-
nn Present at birth, with craniofacial dysmorphism, high
cortical white matter. The T2 signal abnormality often
forehead, ocular anomalies, hepatomegaly, severe
spares the frontal lobes or eventually may involve them
hypotonia, and seizures
as the disease worsens. The abnormal signal is thought
nn Polymicrogyria and pachygyria with occasional
to reflect abnormally high phenylalanine levels and
abnormal clefting
may resolve with adequate dietary control. Involvement
nn Diffuse hypomyelination may be caused by accumu-
of the brainstem and cerebellum is less common but
lation of abnormal compounds in brain, such as very
may occur in the setting of more severe supratentorial
long chain fatty acids and pipecolic acid, or by lack of
abnormalities. Restricted diffusion has been reported
sufficient myelin precursors
within the areas of signal abnormality and may be
nn Controversy as to whether Zellweger syndrome is dis-
related to acute decompensation or very elevated serum
tinct from infantile Refsum disease and neonatal adre-
phenylalanine concentrations. Enhancement is rare
noleukodystrophy (NALD) or whether Zellweger is
because there is no inflammatory component. There
the most severe early-onset form of a common process
may be late volume loss related to white matter atrophy
(Box 10-4).

white matter, including the subcortical U fibers with Is There Early Predilection for the Anterior White
associated cerebral atrophy. The corpus callosum, Matter?
internal capsules, and descending corticospinal tracts Alexander disease is a progressive nonfamilial demy-
can also be involved. There is no abnormal enhance- elinating leukodystrophy characterized by increased
ment, perhaps due to a lack of an inflammatory astrocytic eosinophilic Rosenthal fibers and increased
component to the demyelination/dysmyelination, glial fibrillary acid protein. The rapidly fatal neonatal
although cranial nerve enhancement on MRI has been form presents with early megalencephaly and dispro-
reported. The lack of enhancement allows separation portionate frontal lobe disease. Contrast enhancement
from X-linked adrenoleukodystrophy, which also may occur at the margins of the symmetric bifrontal
 Chapter 10 Metabolic Disorders 387

SECTION III
A B
Figure 10-4 Metachromatic leukodystrophy. A, B: Fluid-attenuated inversion recovery images showing symmetric hyperintense regions in the
periventricular white matter and corpus callosum that has not yet involved the subcortical U fibers. Sparing of the perivascular white matter creates
a tigroid pattern of radiating linear hypointensities (arrows, A), which when seen end-on in the higher white matter can have a spotted leopard
skin pattern (not shown). (Case courtesy of Azad Ghassemi, MD, and Nicholas D’Ambrosio, MD, New York Presbyterian Hospital / Weill Cornell
Medical College, New York, NY.)

BOX 10-3 Metachromatic Leukodystrophy BOX 10-4 Phenylketonuria

nn Autosomal recessive mutations in lysosomal enzyme nn Autosomal recessive mutations of phenylalanine
arylsulfatase A (ARSA), which hydrolyzes intracellular hydroxylase, an enzyme that allows conversion of
sulfatides, or mutation of ARSA cofactor saposin B excess amino acid phenylalanine into tyrosine
nn Accumulation of undegraded sulfatides in oligoden- nn Defective enzyme leads to accumulation of toxic phe-
drocytes and Schwann cells causing demyelination nylalanine compounds that damage the developing
of brain and spinal cord white matter and peripheral brain and can cause mental and growth retardation,
nerves eczema, epilepsy, ”mousy” odor of urine and skin,
nn Late infantile, juvenile, and adult forms and hypopigmentation
nn Infantile form shows most severe and rapidly fatal nn Damage to brain may result from delayed myelination
disease or malformed myelination with spongiotic changes,
nn Late infantile form is the most common, presenting although mental retardation also may be due in part
at 2 years and progressing to death within 4 years to reduced neurotransmitter production as a result of
decreased tyrosine production
nn Treatment involves dietary restriction of phenylalanine
regions of T2 hyperintensity and then progresses pos-
teriorly to the parietal lobes and internal and external
capsules. The subcortical U fibers typically are involved. g­ anglia, corona radiata, and cerebellar dentate nuclei
In the late stages of the disease, cysts may develop. The on CT scan of unknown etiology. Hyperdensity limited
more mild juvenile and adult forms do not show macro- to the thalami may be seen with GM2 gangliosidosis.
cephaly because the head has already formed. The adult Patchy hypodense changes occur in the deep and peri-
form is characterized by areas of T2 hyperintensity and ventricular white matter with early sparing of the sub-
late atrophy of the medulla oblongata and upper spinal cortical white matter. MRI shows corresponding areas
cord (Figure 10-5). The basal ganglia and thalami may of T2 hyperintensity that also involve the cerebellar
also be involved. Hemispheric white matter disease and white matter, cerebellar nuclei, corticospinal tracts, and
patchy enhancement may be seen in patients younger posterior limbs of the internal capsules. The cerebellar
than 40 years (Box 10-5). white matter and deep gray matter changes only occur
in early-onset disease before 2 years. Parietal periven-
Are the Thalami and Basal Ganglia Also Too tricular white matter T2 signal abnormality and corpus
Dense? callosal involvement are seen over time along with late
Globoid cell leukodystrophy (Krabbe disease) can be T2 hyperintensity of the thalami (Figure 10-6). Adult-
separated from other leukodystrophies by early tran- onset disease may present with fewer areas of signal
sient faint hyperdensity within the thalami, basal abnormality, and there have been reports of normal
388 Section III  Problem Solving: Disease Categories

A B
Figure 10-5 Adult-onset Alexander disease. A: Sagittal T2-weighted image showing atrophy and signal abnormalities in the medulla oblongata
(arrow). The hyperintensity fades away in the upper cervical cord, whereas the entire spinal cord is also atrophic. B: Fluid-attenuated inversion
recovery image in another patient showing increased signal intensity of the periventricular white matter, which is more extensive in the posterior
regions. (From Pareyson D, Fancellu R, Mariotti C, et al. Adult-onset Alexander disease: a series of eleven unrelated cases with review of the litera-
ture. Brain 2008;131:2321-2331.)

within the symmetric and patchy white matter lesions

BOX 10-5 Alexander Disease (Fibrinoid (Figure 10-7 and Box 10-7).
­Leukodystrophy) Megaloencephalic leukoencephalopathy (MLC) with
nn Mutation of glial fibrillary acid protein on chromo- subcortical cysts is a slowly progressive disease that pres-
some 17q21 ents with early diffuse brain swelling in infancy. The white
nn Pathologic features are increased astrocytic eosino- matter changes follow a centripetal course, with severe
philic Rosenthal fibers in subependymal, subpial, and peripheral changes characterized by early large subcorti-
perivascular regions cal cysts, particularly in the frontal parietal and temporal
nn Glial fibrillary acid protein increases lobes. The subcortical cysts and white matter lesions show
nn Periventricular rim of high signal intensity T1, low facilitated diffusion with high apparent diffusion coeffi-
signal intensity T2 cient (ADC) as well as decreased FA at DTI. The cortical
and deep gray matter structures are spared (Box 10-8).
The central cystic changes of Lowe syndrome and the
peripheral cystic changes of MLC should be ­differentiated
MRI scans or initial T2 hyperintensity limited to the from the diffuse cribriform dilated perivascular spaces
bilateral corticospinal tracts and posterior corpus cal- of the mucopolysaccharidoses. The cystic destruction in
losum. Bilateral isolated corticospinal tract abnormali- advanced Alexander disease and Leber hereditary optic
ties are also seen in amyotrophic lateral sclerosis. The neuropathy has strong frontal lobe predominance.
globoid cells of Krabbe disease can cause enlargement
of the optic nerves and enhancement of cranial nerves Peripheral White Matter Disorders
(Box 10-6).
The thalami and basal ganglia may show hyperin- Is There Early Subcortical White Matter Disease?
tense abnormalities in the peripheral white matter leu- Leukodystrophies with early subcortical white matter
kodystrophies, as in Alexander disease and Canavan involvement include Alexander disease, Canavan dis-
disease. ease, and galactosemia. The subcortical U fibers may be
abnormal in Cockayne syndrome, but their involvement
Are There Cystic Lesions within the Involved usually occurs later.
White Matter? Canavan disease is a spongiform or vacuolating
The diagnosis of Lowe syndrome usually is made based myelinopathy that shows diffuse demyelination that
on clinical findings at birth; thus this disease does not classically shows subcortical U-fiber white matter T2
typically present an imaging or diagnostic quandary. hyperintense changes and symmetric involvement of the
There is nonenhancing central white matter T2 signal globi pallidi and thalami. The white matter disease has
hyperintensity that spares the subcortical U fibers. Mul- a centripetal progression pattern that extends into the
tiple cystic or punctate CSF signal lesions can be found central white matter as well as the internal and ­external
 Chapter 10 Metabolic Disorders 389

SECTION III
A B
Figure 10-6 Late-infantile Krabbe disease. A, B: Axial T2-weighted images through the basal ganglia showing involvement of the occipital
white matter and posterior limbs of the internal capsules (curved arrows, A). The thalamus and globus pallidus show symmetric decreased signal.
The midbrain reveals small cerebral peduncles and increased signal along the course of the corticospinal tract (arrows, B). (From Zafeiriou DI,
Michelakaki EM, Anastasiou AL, Gombakis NP, Kontopoulos EE. Serial MRI and neurophysiological studies in late-infantile Krabbe disease. Pedi-
atr Neurol 1996;15:240-244.)

elevation in NAA, whereas MLC typically develops

BOX 10-6 Krabbe Disease (Globoid Cell prominent subcortical cysts.
­Leukodystrophy)
nn Autosomal recessive mutation of galactosylceramide Are the Subcortical U Fibers and Bilateral Optic
β-galactosidase (GALC) at chromosomal location Nerves Involved?
14q24 Bilateral optic nerve involvement is typical for Leber
nn GALC deficiency leads to cytotoxic accumulation of hereditary optic neuropathy, a maternally inherited mito-
cerebrosides within oligodendrocytes and Schwann chondrial disorder. Patients present with severe acute or
cells causing demyelination of central nervous system subacute bilateral visual loss in early adulthood. Although
and spinal cord white matter and peripheral nerves the disease usually is isolated to the optic nerves, some
nn Clinical subtypes (infantile, late infantile, juvenile, patients have Leber hereditary optic neuropathy plus dis-
adult) categorized by age of onset, with infantile form eases with widespread involvement of the central nervous
most common system (CNS). They include multiple sclerosis-like demy-
nn Later-onset forms may be due to less severe reduc- elinating disease with otherwise indistinguishable lesions
tions in GALC activity, and the disease may be inci- of the brain and spinal cord, Leigh-like encephalopathy
dentally diagnosed in midlife due to presence of gait with lesions of the brainstem, and dystonia disease with
unsteadiness, paraparesis, or hyperreflexia striatal necrosis in children. Patients may also demonstrate
striking symmetric cystic destruction in the frontal lobes
involving the subcortical U fibers and in the anterior cor-
capsules (Figure 10-8). This demyelinating process is pus callosum (Figure 10-9). The frontal lobe lesions with
not accompanied by abnormal enhancement. Late cyst formation may mimic Alexander disease (also shows
disease may show tiny cysts in the subcortical U-fiber early subcortical U-fiber involvement) and MLC (reveals
layer. MR spectroscopy shows a dramatic increase in early sparing of subcortical U fibers), both of which cause
N-acetylaspartate (NAA) that contrasts with the nearly macrocephaly in the infantile form (Box 10-11).
universal decrease in almost all other white matter
­diseases (Box 10-9). Nonspecific, Diffuse, Other
Galactosemia shows areas of T2 hyperintensity in the
cerebral peripheral white matter with delayed myelina- Is There a “Tigroid” Pattern of the Perivascular
tion and diffuse atrophy (Box 10-10). White Matter?
The tigroid pattern is formed by linear T2 hypointense
Is Macrocephaly Present? stripes of spared perivascular white matter that extend
Subcortical white matter disease and macrocephaly are from the ventricles in a radial pattern. This pattern is
seen in the infantile forms of Canavan disease, Alexan- seen in metachromatic leukodystrophy, Pelizaeus-Mer-
der disease, and MLC. Canavan disease has a unique zbacher disease, and trichothiodystrophy. The tigroid
390 Section III  Problem Solving: Disease Categories

100

80

60

40

20

–20

–40
A B 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
Figure 10-7 Lowe syndrome. A: Fluid-attenuated inversion recovery image revealing periatrial hyperintensities with multiple small, cyst-like
structures. B: Spectrum from the left periatrial region showing the peak of myoinositol (at 3.56 ppm) is greater (arrow) than that of nearby choline
(at 3.22 ppm). (From Sener RN. Lowe syndrome: proton MR spectroscopy, and diffusion MR imaging. J Neuroradiol 2004; 31:238-240.)

BOX 10-7 Lowe Syndrome (Oculocerebrorenal BOX 10-8 Megaloencephalic Leukoencephalopa-

Syndrome [OCRL]) thy with Subcortical Cysts (van der
Knaap disease)
nn X-linked recessive mutations of OCRL1 on chromo-
some Xq26 nn Autosomal recessive
nn OCRL1 encodes a Golgi body protein that modulates nn Myelin splitting and intramyelinic vacuolization
cellular trafficking and cytoskeleton remodeling nn >60 mutations in MLC1 gene on chromosome
nn High death rate in first months of life with failure to 22q13.33
thrive, electrolyte imbalances, seizures, and recurrent nn Slow clinical progression despite marked radio-
pneumonias graphic abnormalities
nn Present at birth with cataracts, hypotonia, absent
deep tendon reflexes, and typical facies

demonstrate decreased FA (Figure 10-11). The structural

pattern may be caused by sparing of myelin in the abnormalities are otherwise usually mild despite severe
perivascular areas in the setting of diffuse white matter clinical disabilities. They include mild nonspecific atro-
abnormality (Figure 10-4). phy of the cerebrum, cerebellum, and brainstem and
areas of T2 hyperintensity in the hemispheric white mat-
Is There Diffuse Hypomyelination? ter, striatum, and brainstem (Box 10-13).
Pelizaeus-Merzbacher disease shows diffuse hypomy-
elination of the central and peripheral white matter that Is There Diffuse Cerebral, Cerebellar, and
resembles the appearance of a newborn brain. Some Brainstem Disease?
myelination may occur and then disappear with dis- Maple syrup urine disease demonstrates diffuse white
ease progression. The most severe form is the “conna- matter hypodensity that is more marked in the cerebel-
tal” or infantile form, which presents at birth without lum and brainstem than in the cerebral hemispheres.
any evidence of myelination (Figure 10-10). There is This edema may be seen on transfontanelle ultrasound
no abnormal enhancement or evidence of white mat- as diffuse white matter echogenicity. Early on, maple
ter destruction. Late in the disease, there may be diffuse syrup urine disease can also present with a normal CT
white matter atrophy (Box 10-12). scan. MRI shows T2 hyperintense changes in the deep
cerebellar white matter and dorsal brainstem, cerebral
Is There Severe Atrophy of the Superior peduncles, posterior limbs of the internal capsule and
Cerebellar Peduncles? corticospinal tracts (to the cortex), and, to a lesser extent,
Myoclonus epilepsy with ragged red fibers (MERRF) the supratentorial white matter and occasionally globus
may present with severe atrophy that is limited to the pallidi (Figure 10-12). Some of this signal abnormality
superior cerebellar peduncles, which by DTI can also may be related to cerebral edema from ­hyponatremia
 Chapter 10 Metabolic Disorders 391

SECTION III
NAA

Ins

Cr/PCr
Lac + Lip
Cho

Chemical shift (ppm)

A

Figure 10-8 Canavan disease. Short (A) and long (B) TE

spectra showing diffuse white matter changes and a nearly
pathognomonic increase in N-acetylaspartate, which is
nearly double the normal values from age-matched controls
and even higher than the value seen in adults. (From Dezor-
Chemical shift (ppm) tova M, Hajek M. 1H MR spectroscopy in pediatrics. Eur J
B Radiol 2008;67:240-249.)

BOX 10-9 Canavan Disease (Spongiform BOX 10-10 Galactosemia

­Leukoencephalopathy, Canavan–van
Bogaert-Bertrand disease) nn Autosomal recessive disorder
nn Kinase, transferase, or epimerase deficiency; most
nn Autosomal recessive common is galactose-1-phosphate-uridyl transferase
nn Increased N-acetylaspartate due to deficiency of aspar- deficiency
toacylase on chromosome 17p nn Treatment is dietary restriction of galactose
nn Infantile form >> congenital and juvenile forms
392 Section III  Problem Solving: Disease Categories

A B
Figure 10-9 Leber hereditary optic neuropathy. Axial T2-weighted (A) and sagittal T1-weighted images (B) showing destructive cystic lesions in
the frontal lobe deep and subcortical white matter. The genu and the rostral third of the corpus callosum are severely involved. (From Kovacs GG,
Hoftberger R, Majtenyi K, et al. Neuropathology of white matter disease in Leber’s hereditary optic neuropathy. Brain 2005;128:35-41.)

v­ irtually any end-stage white matter disease. Nonke-

BOX 10-11 Leber Hereditary Optic Neuropathy totic hyperglycemia is a hereditary amino acidopathy
nn Most common mitochondrial disorder to affect vision characterized by glycine accumulation. Patients pres-
(acute or subacute) ent in early infancy with diffuse volume loss, abnormal
nn >30 point mutations in mitochondrial DNA (11,778 white ­matter, thinned corpus callosum, and delayed
>> 3460 > 14,484) myelination. The urea cycle disorders include ornithine
nn Males >> females; 40% in children carbamyl transferase deficiency, carbamyl phosphate
nn Bilateral optic nerve atrophy with degeneration of synthetase deficiency, arginosuccinic aciduria, citrul-
retinal ganglion cells and optic nerve axons linemia, and hyperargininemia. These disorders of
increased ammonemia manifest with diffuse cerebral
edema that involves the cortex and white matter, includ-
ing the subcortical U fibers that develops into diffuse
and may resolve with therapy or progression to sub- white matter lesions and marked atrophy.
acute stage. Diffusion imaging shows restricted diffu- Chemotherapy and radiation therapy often show early
sion within the areas of T2 signal abnormality acutely, central white matter changes, although the subcortical U
particularly the ventral lateral thalami, posterior limbs fibers may also be involved with diffuse toxic effects. The
of the internal capsules, and globus pallidi. Contrast destruction of intrinsically normal myelin usually is asym-
enhancement is not present because there is no inflam- metric, with T2 hyperintense lesions that do not show sig-
matory component (Box 10-14). nificant mass effect or enhancement (Figure 10-14).
Central pontine myelinolysis is an acquired disorder
that classically demonstrates abnormal T2 hyperinten- Are Dilated Perivascular Spaces Present?
sity within the central pons that spares the peripheral Mucopolysaccharidosis is the only metabolic disor-
brainstem and corticospinal tracts (Figure 10-13). This der to have dilated perivascular spaces in a symmetric
entity is more accurately referred to as osmotic demy- cribriform pattern, although this may be seen in other
elination syndrome due to the common involvement of nonmetabolic disorders. The dilated perivascular spaces
­extrapontine structures, including the basal ganglia, may involve the periventricular white matter, thalami,
cerebral white matter (including subcortical U fibers), basal ganglia, corpus callosum, and brainstem (Figure
cerebellar peduncles, and cortex. Imaging abnormalities 10-15). They are thought to result from the macro-
may lag behind clinical symptoms; restricted diffusion scopic accumulation of glycosaminoglycans, although
may occur prior to T2 hyperintense lesions. they also may reflect defective CSF resorption as part
of communicating hydrocephalus. Other abnormalities
Other of impaired CSF resorption include enlarged subarach-
Nonspecific white matter patterns (diffuse, unilat- noid spaces, arachnoid cysts, and mega cisterna magna.
eral, bilateral, asymmetric) can be seen with nonke- Brain abnormalities include diffuse atrophy and areas
totic hyperglycinemia, the urea cycle disorders, and of T2 hyperintensity in the periventricular white
 Chapter 10 Metabolic Disorders 393

SECTION III
A B
Figure 10-10 Pelizaeus-Merzbacher disease. Axial T1-weighted (A) and T2-weighted (B) images showing diffuse hypomyelination with abnor-
mal T2 hyperintensity of the cerebral white matter. (Case courtesy of Yvonne W. Lui, MD, Montefiore Medical Center, New York, NY.)

BOX 10-12 Pelizaeus-Merzbacher Disease

Is the White Matter More T2 Bright than the
Gray Matter?
nn X-linked recessive disorder of proteolipid protein 1 Although white matter lesions and atrophy are variably
(PLP1) gene on chromosome Xq22 present in all the poliodystrophies, the white matter
nn Pelizaeus-Merzbacher disease and spastic paraplegia disease may be the most severe in NCL. Infantile NCL,
2 (SPG2) share PLP1 gene defects along a spectrum, which is the most severe form of NCL, causes extreme
with SPG2 showing milder and later onset symptoms cortical atrophy and marked white matter T2 hyperin-
nn PLP1 proteolipid protein makes up 50% of protein tensity that becomes higher than that of gray matter. The
mass of myelin in oligodendrocytes progressive cortical atrophy is most marked in the cer-
nn Defective folding or transport of PLP to cell surface ebellum and frontal lobes. The white matter changes are
results in PLP accumulation that leads to oligoden- thought to reflect myelin loss, wallerian degeneration,
drocyte and axonal cell death and gliosis after neuronal death. These changes occur
rapidly during the first 4 years of life in parallel with
clinical and histopathologic progression. The thalamus
­ atter, which along with the hydrocephalus correlate
m shows T2 hypointensity in infantile NCL and variant
with disease duration and severity (Figure 10-16 and subtype (not classic) late infantile NCL. Late infantile
Box 10-15). NCL shows extensive T2 hyperintense lesions in the
hemispheric white matter including the internal cap-
PART II: CORTICAL GRAY MATTER sule. Whole-brain ADC measurements reveal facilitated
diffusion (increasing ADC values) in patients with late
DISEASE
infantile NCL that correlates with disease severity and
Poliodystrophies or disorders of the cortical gray matter duration; ADC values normally decrease with increasing
often manifest with marked cortical atrophy and sulcal age due to normal myelination (Box 10-17).
widening. Disorders include Alpers syndrome, Menkes
syndrome, and neuronal ceroid lipofuscinosis (NCL). Vari- PART III: DEEP GRAY MATTER
able white matter lesions and atrophy are often present.
DISEASE
Alpers syndrome usually affects infants and very
young children with progressive neurologic disorders, The combination of deep gray matter disease and periph-
including refractory epilepsy and severe liver disease. eral white matter disease in a child or young adult strongly
Older children and teenagers may have juvenile Alpers suggests the diagnosis of a mitochondrial disorder. Mito-
syndrome, which has a more protracted clinical course. chondrial disorders represent a spectrum of clinically
The brain shows necrotizing lesions with severe neuro- similar diseases that involve mutations in mitochondrial
nal loss and gliosis, decreased white matter volume, and or nuclear deoxyribonucleic acid (DNA). Mitochondrial
delayed myelination. Marked cortical thinning is most DNA has a maternal inheritance pattern. Mutations in
conspicuous in the posterior temporal, occipital, and mitochondrial DNA result in marked ­phenotypic hetero-
frontal lobes (Figure 10-17 and Box 10-16). geneity due to heteroplasmy, in which variable amounts
394 Section III  Problem Solving: Disease Categories

A B

Figure 10-11 Myoclonus epilepsy with ragged red fibers.

T2-weighted images showing characteristic severe atrophy of
the superior cerebellar peduncles (arrows). Mild diffuse atrophy
C and symmetric areas of hyperintensity are present in the medial
thalami and periaqueductal gray matter.

BOX 10-13 Myoclonus Epilepsy with Ragged Red Fibers (MERRF)

nn Myoclonus epilepsy, cerebellar ataxia, myopathy, and hearing loss
nn A8344G >> A3243G mitochondrial DNA mutations
nn A8344G is associated with slower, less severe disease than A3243G
nn No cerebral lactic acidosis and no stroke-like episodes (unlike MERRF)
nn Radionuclide single-photon emission computed tomography shows decreased, potentially reversible perfusion, par-
ticularly in the parietal occipital lobes (normal perfusion in most other mitochondrial disorders)
nn Diffusion tensor imaging reveals decreased fractional anisotropy in the abnormal areas of the brain and spinal cord,
although fiber tracking may be preserved
 Chapter 10 Metabolic Disorders 395

SECTION III
A B
Figure 10-12 Maple syrup urine disease. Axial T2-weighted images showing diffuse hyperintense T2 signal involving the supratentorial white
matter, basal ganglia, mesencephalon, and cerebellum. (From Schönberger S, Schweiger B, Schwahn B, Schwarz M, Wendel U. Dysmyelination in
the brain of adolescents and young adults with maple syrup urine disease. Mol Genet Metab 2004;82:69-75.)

BOX 10-14 Maple Syrup Urine Disease (MSUD)

nn Multiallelic autosomal recessive disorder of the mitochondrial enzymatic complex
nn Neurotoxic accumulation of branched-chain amino acids (BCAA) and their ketoacid metabolite forms
nn Excess BCAA in urine gives urine a maple syrup smell
nn Five clinical phenotypes: classic, intermediate, intermittent, thiamin-responsive, and dihydrolipoamide dehydroge-
nase (E3) deficient
nn Classic form has the most severe BCAA defect (<2% enzymatic activity) and presents within the first week of life
nn Treatment involves restriction of dietary BCAA and/or oral thiamine

Figure 10-13 Central pontine myelinolysis. Axial T2-weighted

image showing central hyperintensity and swelling that spares the
peripheral brainstem.
396 Section III  Problem Solving: Disease Categories

A B
Figure 10-14 Methotrexate-based chemotherapy– and radiation therapy–induced necrotizing encephalopathy in a patient with treated brain
and leptomeningeal metastases from non–small cell lung carcinoma. A, B: Fluid-attenuated inversion recovery images showing diffuse areas of
hyperintensity involving the cerebral white matter, basal ganglia, cerebellum, and brainstem. Susceptibility artifact over the right sylvian region is
due to an Ommaya reservoir (not shown).

A B
Figure 10-15 Mucopolysaccharidosis type IH (Hurler syndrome). Computed tomography (A) and T2-weighted images (B) showing cribriform
dilated perivascular spaces in the hemispheric white matter as well as small cysts in the basal ganglia.
 Chapter 10 Metabolic Disorders 397

SECTION III
A B
Figure 10-16 Mucopolysaccharidosis type IIA (Hunter syndrome). Axial fluid-attenuated inversion recovery images. A: Initial image showing
cerebral atrophy, communicating hydrocephalus, and symmetric areas of hemispheric white matter hyperintensity, which all progressed after 1
year (B). (Case courtesy of Vinh Nguyen, MD, Long Island Jewish Medical Center, New Hyde Park, NY.)

BOX 10-15 Mucopolysaccharidosis (MPS) syndrome; Kearns-Sayre syndrome (KSS); mitochondrial

myopathy, encephalopathy, lactic acidosis, and stroke
nn Heterogeneous group of lysosomal storage disorders (MELAS); MERRF; mitochondrial neurogastrointestinal
nn Accumulation of incompletely degraded glycosami- encephalopathy; and Leber hereditary optic neuropathy.
noglycans in multiple organs The abnormal white matter may include small cyst-like
nn Autosomal recessive, except for MPS II (X-linked lesions and involvement of the cerebral and cerebellar
recessive) white matter. This should be contrasted from the leu-
nn Seven discrete MPS disorders, caused by 11 lysosomal koencephalopathies, which primarily involve the deep
enzyme deficiencies cerebral white matter with relatively less involvement of
nn α-l-Iduronidase deficiency on chromosome 4p16.3 the deep gray nuclei.
shared by severe MPS IH (Hurler syndrome), inter- Disorders of the deep gray matter may be separated
mediate MPS IHS (Hurler-Scheie), and mild MPS IS by primary (or mixed) involvement of the individual
(Scheie) components of the basal ganglia (caudate, putamen,
nn MPS IH Hurler syndrome is the prototype MPS dis- corpus striatum [caudate and putamen], globus palli-
order dus) and of the thalamus.
nn Severe MPS with mental retardation: MPS IH (Hurler),
MPS IIA (Hunter), MPS III (Sanfilippo), MPS VII
Caudate Nucleus
nn MPS IV (Morquio) spares the central nervous system
Are the Caudate Nuclei Atrophic?
Marked disproportionate atrophy of the caudate nuclei
of mutant and normal copies are present in each cell is the imaging hallmark of Huntington disease. Severe
through the process of replicative segregation. Ragged red neuronal loss may also involve the putamen and less
fibers may be found in many of these disorders, although so the globus pallidus (Figure 10-18). The caudate
only one incorporates this descriptive terminology into nucleus atrophy results in ex vacuo dilatation of the
its name (myoclonic epilepsy associated with ragged red frontal horns, which assume a boxcar-like configura-
fibers) (Table 10-3). Mitochondrial encephalopathies tion, and increased bicaudate ratio (minimum inter-
often involve the globus pallidus, which may be more caudate distance divided by brain width, measured on
susceptible to injury due to the relatively high baseline an axial image at level of third ventricle). Early disease
metabolism of the pallidal neurons. shows areas of T2 hyperintensity in the caudate heads
The white matter is commonly abnormal, with areas and putamina prior to the atrophy. The striatum may
of T2 hyperintensity that may spontaneously resolve and also show areas of T2 hypointensity due to iron depo-
subsequently recur. These changes are thought to reflect sition. Advanced Huntington disease has generalized
either mitochondrial cerebral angiopathy–induced involvement of the brain with diffuse cerebral atrophy
ischemia or mitochondrial impairment–induced direct that often begins in the frontal lobes and has posterior
neuronal death. White matter disease occurs in Leigh progression (Box 10-18).
398 Section III  Problem Solving: Disease Categories

A B
Figure 10-17 Alpers syndrome. A: Sagittal T1-weighted image showing diffuse atrophy. B: Axial T2-weighted image showing hyperintense
lesions in the white matter. (Case courtesy of Sasan Karimi, MD, Memorial Sloan-Kettering Cancer Center, New York, NY.)

BOX 10-16 Progressive Cerebral Poliodystrophy BOX 10-17 Neuronal Ceroid Lipofuscinosis (NCL)

(Alpers, Alpers-Huttenlocher Syn-
drome) nn Heterogeneous group of genetically distinct progres-
sive diseases
nn Progressive neuronal degeneration of childhood with nn Abnormal intracellular lipid pigment (lipofuscin)
liver disease accumulation in lysosomes of different cells, includ-
nn Autosomal recessive hepatocerebral disorder ing neurons, lymphocytes, vascular endothelium, and
nn Heterogeneous group of similar clinical and meta- muscle
bolic disorders nn Four major types (>20 different types described):
nn Spongiform atrophy of cortex (particularly occipital 1. Infantile NCL (Santavuori-Haltia disease)
lobes), basal ganglia, and thalami 2. Late infantile NCL (Jansky-Bielschowsky disease)
3. Juvenile NCL (Batten or Spielmeyer-Vogt-Sjögren-
Trichopoliodystrophy (Menkes, Menkes kinky hair
Batten disease)
disease)
4. Adult NCL (Kufs or Parry disease)
nn X-linked recessive mitochondrial disorder that only
nn Juvenile NCL is the most common type (Batten occa-
affects male infants
sionally used to refer to all NCLs)
nn Decreased copper absorption results in poor cyto-
nn Childhood NCLs are autosomal recessive (infantile,
chrome oxidase activity
late infantile, juvenile)
nn Secondarily abnormal mitochondria
nn Adult NCLs are autosomal recessive (Kufs) or domi-
nn Kinky hair term arises from the coarse, stiff, and frayed
nant (Parry)
hair ends
nn More mild and slowly progressive than childhood
nn Rapidly progressive atrophy with ventriculomegaly
forms
and cortical thinning
nn Weill Cornell late infantile NCL scale incorporates
nn Cortical shrinking and subsequent stretching of the
quantitative magnetic resonance imaging criteria
subdural vessels may contribute to bilateral subdural
(apparent diffusion coefficient values, ventricular vol-
hematomas, which should not be mistaken for non-
umes) to monitor disease
accidental trauma
 Chapter 10 Metabolic Disorders 399

SECTION III
Table 10-3 Ragged Red Fibers BOX 10-18 Huntington Disease
nn  uscle biopsy using the modified Gomori trichome stain
M nn Autosomal dominant, complete penetrance
nn Appearance caused by increased abnormal mitochondria, lack nn Classic adult form presents at 35–45 years and is fatal
of cytochrome c oxidase, and mitochondrial DNA deletions within 20 years
nn Morphologic characteristic of mitochondrial nn Less common juvenile form in 1%–6% that presents
­encephalomyopathies
before age 20 years with Parkinson-like movements
nn Myoclonus epilepsy with ragged red fibers
and rigidity rather than choreoathetoid movements
nn Mitochondrial myopathy, encephalopathy, lactic acidosis,
and stroke nn Huntington disease gene on chromosome 4p16.3
nn Repeat expansion of CAG (cytosine-adenosine-­
nn  earns-Sayre syndrome/chronic progressive external
K
­ophthalmoplegia guanosine) trinucleotide; earlier age of onset and
nn Menkes syndrome
more rapidly progressive disease occur with increased
repeats
nn Toxic accumulation of mutant Huntington protein
nn Impaired energy metabolism primarily affects the
medium spiny GABAergic neurons in the striatum
and less so the mesencephalon and cortex

reticulata of the substantia nigra. Linear hyperintensities

may involve the dentatorubrothalamic, pontocerebellar,
and corticospinal tracts. Patchy cortical and subcortical
lesions may occur, particularly in the frontal lobes. Gen-
eralized brain atrophy, particularly midbrain atrophy,
usually is present (Box 10-19).
Isolated hyperintensity of the corpus striatum may
be seen in a variety of metabolic diseases, such as Leigh
syndrome and MELAS, as well as other acquired meta-
bolic diseases, including thiamine deficiency and infec-
tions such as CNS aspergillosis (Figure 10-20). However,
Leigh syndrome will classically show brainstem and cer-
ebellar disease.
The putamen and thalamus are preferentially
involved by severe hypoxic–ischemic encephalopathy,
which may be due to increased activity of excitatory
glutamatergic pathways. The globus pallidus may be
Figure 10-18 Huntington disease. Axial computed tomographic
protected in those situations by inhibitory neuronal
image showing severe caudate nucleus atrophy and subsequent ex activity, although the relatively high baseline activity of
vacuo, boxcar-like configuration of the frontal horns of the lateral ven- the pallidal neurons may make them more vulnerable
tricles. Widening of the frontal extraaxial cerebrospinal fluid spaces is to subacute oxidative stresses, such as the mitochondrial
present. Diffuse cerebral atrophy often begins in the frontal lobes and encephalopathies and kernicterus.
progresses posteriorly. (Case courtesy of Yvonne W. Lui, MD, Monte-
fiore Medical Center, New York, NY.)
Are the Brainstem and Spinal Cord Also
Abnormal?
Corpus Striatum (Caudate Nucleus Leigh syndrome shows hyperintense putamina in nearly
all cases, with classic involvement of the basal ganglia,
and Putamen)
brainstem, and spinal cord. Symmetric gray and white
Are the Putamina Too Bright? matter T2 hyperintense lesions may also involve the
Wilson disease shows symmetric regions of T2 hyper- caudate nuclei, globi pallidi, midbrain tegmentum, peri-
intensity or mixed signal intensity in the putamina aqueductal gray matter, pons, cerebral peduncles, and
and globi pallidi, caudate nuclei, and thalami (Figure posterior column spinal cord (Figure 10-21). The basal
10-19). The putamina often show peripheral, laminar ganglia is usually the site of initial involvement. The
rims of T2 hyperintensity. The hyperintense areas reflect upper brainstem lesions are often transient and in par-
the portal–systemic encephalopathic effects of Wilson allel to reversible respiratory distress, whereas the lower
disease, whereas the hypointense areas represent copper brainstem lesions are usually present at the time of near-
deposition. The excess copper does not cause CT hyper- fatal respiratory failure. The lesions may resolve after sev-
density. These structures show restricted diffusion in the eral months, or they may progress to cavitary gliosis. Mild
acute phase. Midbrain abnormalities may give the giant or absent basal ganglia lesions with bilateral subthalamic
panda sign, which consists of tegmentum hyperinten- nuclei and brainstem lesions may suggest cytochrome c
sity and superior colliculus hypointensity with sparing oxidase (COX) deficiency and underlying SURF1 gene
of the red nucleus and the lateral portions of the pars mutations. The white matter is spared in Leigh syndrome,
400 Section III  Problem Solving: Disease Categories

A B
Figure 10-19 Wilson disease. T2-weighted images showing symmetric areas of hyperintensity in the putamina, thalami, and midbrain. (Case
courtesy of Yvonne W. Lui, MD, Montefiore Medical Center, New York, NY.)

­ eurologic cretinism) may also show hypointensity of

n
BOX 10-19 Hepatolenticular Degeneration the globi pallidi and substantia nigra. Chronic hemo-
­(Wilson Disease) chromatosis may show globus pallidus hypointensity.
nn Autosomal recessive
nn Deficient ceruloplasmin (serum transport protein Are the Globi Pallidi Too Bright?
for copper) due to ATP7B mutation on chromosome KSS and chronic progressive external ophthalmoplegia
13q14.3-q21.1 are related diseases that involve both gray and white
matter structures. Patients classically present with
abnormal globi pallidi and subcortical white matter;
the typical involvement of the subcortical U fibers and
in contrast to the diffuse white matter and brainstem sparing of the central or periventricular white matter are
involvement of maple syrup urine disease (Box 10-20). important features distinguishing KSS from the leuko-
dystrophies. Areas of T2 hyperintensity may be seen in
Is the Cortex Also Abnormal? the other basal ganglia structures, thalamus, brainstem
Creutzfeldt-Jakob disease is a rapidly progressive, fatal, tegmentum, and cerebellar white matter (Figure 10-23).
potentially transmissible spongiform encephalopathy Diffuse atrophy is the most common imaging finding,
caused by prion infection. Both deep and superficial with good correlation between the severity of cerebel-
gray matter structures, including the caudate nuclei, lar atrophy and cerebellar signs and symptoms but poor
putamina, thalami, and cerebral cortex, show T2 hyper- correlation between cerebral and brainstem atrophy.
intensity and diffusion restriction (Figure 10-22). Sym- Increased lactate in the abnormal white matter supports
metric hyperintensity of the dorsomedial and pulvinar the mitochondrial respiratory chain insufficiency theory
thalamic nuclei (hockey-stick sign) is characteristic for (Box 10-21).
new variant Creutzfeldt-Jakob disease. The globi pallidi Cockayne syndrome is an inherited disorder of
are usually spared. DNA repair that shows dense calcifications of the basal
ganglia (particularly the globus pallidus and putamen)
Globus Pallidus and dentate nuclei in the cerebellum. The basal ganglia
and dentate nuclei calcifications present with hyperin-
Are the Globi Pallidi Too Dark? tense areas on T1 and hypointense areas on T2-weighted
The metal deposition diseases typically cause symmet- images. The basal ganglia calcifications should be distin-
ric areas of T2 hypointensity in the globi pallidi, among guished from mild physiologic calcifications that occur
other structures. Neurodegeneration with brain iron with normal aging and other causes such as infection.
deposition (NBIA) may show an eye-of-the-tiger appear- Patchy areas of T2 hyperintensity are also seen in the
ance due to focal anterior medial hyperintensity in the periventricular white matter, usually with late involve-
otherwise hypointense globi pallidi (see below). Wil- ment of the subcortical U fibers, and in the thalami. The
son disease is accompanied by laminar hyperintensity diffuse white matter changes tend to spare the corpus
of the putamina. Hypothyroidism in children (endemic callosum (Box 10-22).
 Chapter 10 Metabolic Disorders 401

SECTION III
A B
Figure 10-20 Thiamine deficiency. A: Fluid-attenuated inversion recovery image revealing symmetric hyperintensity and swelling of the basal
ganglia. B: Diffusion-weighted image showing diffusion restriction in the globi pallidi and putamina.

The globus pallidus is often involved by the leuko-

Thalamus
dystrophies, usually in conjunction or following the
white matter lesions. Canavan disease may present Are the Thalami Too Dense/Dark?
with symmetric areas of T2 hyperintensity in the globi Both Krabbe disease and GM2 gangliosidosis (Tay-Sachs
pallidi that precede the typical peripheral white matter disease, Sandhoff disease) share the appearance of symmet-
changes. ric hyperdense thalami on CT scan. The hyperdensity and
Kernicterus or bilirubin encephalopathy in infants corresponding MR T1 hyperintensity and T2 hypointensity
presents with areas of T2 hyperintensity in the globi result from abnormal calcium deposition. Krabbe disease
pallidi, subthalamic nuclei, and hippocampi (Figure reveals hyperdensity of other structures and more extensive
10-24). A similar appearance may be found in hepatic white matter changes that include the corpus callosum.
encephalopathy and hyperalimentation (due to man- The hyperdense thalami of GM2 gangliosidosis occur
ganese in total parenteral nutrition). Similar appear- only in the infantile form. The diffuse patchy and con-
ances may be caused by methylmalonic acidemia, fluent T2 hyperintense hemispheric white matter lesions
propionic acidemia, creatine deficiency, carbon mon- tend to spare the internal capsule. The T2 hyperintense
oxide poisoning, toxic including chemotherapeutic lesions demonstrate centripetal progression and may
insults, and hypoglycemia. The toxic and ischemic involve the basal ganglia, cerebellum, and brainstem.
exposures may often be distinguished based on the Severe cerebellar atrophy is characteristic for juvenile GM2
clinical scenario. gangliosidosis, which may also show mild preceding cere-
bral atrophy, callosal thinning, and white matter lesions
Are the Globi Pallidi Too Dark and Too Bright? (Figure 10-26). Adult GM2 gangliosidosis may present
The eye-of-the-tiger sign is formed by focal anterior with only progressive cerebellar atrophy and otherwise
medial T2 hyperintensity and surrounding T2 hypoin- normal-appearing supratentorial structures (Box 10-24).
tensity in the globus pallidus. The low signal intensity The metal deposition disorders, such as NBIA
is due to iron deposition, whereas the central high sig- (Hallervorden-Spatz), may also cause T2 hypointensity
nal intensity is due to loose tissue with axonal vacuol- of the thalamus, along with hypointensity of the basal
ization. This sign is characteristic for the pantothenate ganglia and brainstem. Infantile NCL and variant sub-
kinase-associated neurodegeneration (PKAN) form of type late infantile NCL may show T2 hypointensity of
NBIA, which was formerly known as Hallervorden- the thalamus, but as part of the poliodystrophies they
Spatz syndrome (Figure 10-25). Early isolated T2 are characterized by marked global gray matter loss and
hyperintensity of the globi pallidi may also be found. cortical atrophy.
PKAN patients have prevalent but late radiographic
evidence of substantia nigra pars reticulata iron depo- Are the Thalami Too Bright?
sition and less marked cerebral and cerebellar atrophy Various diseases may result in T2 hyperintensity of the
than non-PKAN patients. No specific imaging features thalami, including the leukodystrophies (Canavan dis-
have been described for mutation-negative patients ease) and poliodystrophies (Alpers syndrome). Hyperin-
(Box 10-23). tensity is not as useful a diagnostic sign as hypointensity.
402 Section III  Problem Solving: Disease Categories

A B

C D
Figure 10-21 Infantile-type Leigh disease. T2-weighted images showing symmetric areas of hyperintensity in the basal ganglia, thalami, mid-
brain, and medulla. Abnormalities in the midbrain include the cerebral peduncles and periaqueductal gray matter. (Case courtesy of Vinh Nguyen,
MD, Long Island Jewish Medical Center, New Hyde Park, NY.)

BOX 10-20 Subacute Necrotizing Encephalomyelopathy (Leigh Disease, Leigh Syndrome)

nn Autosomal recessive >> X-linked or mitochondrial DNA (maternal)
nn Multiple mitochondrial DNA mutations and enzyme defects, including pyruvate dehydrogenase complex deficiency
and cytochrome c oxidase deficiency
nn Leigh disease refers to patients with classic pathologic findings
nn Leigh syndrome refers to related genetic and biochemical disorders with similar clinical features
nn Infantile type presents before age 2 years with hypotonia, failure to thrive, nystagmus, and respiratory failure
nn Less common juvenile and adult types present with more mild progressive neurologic problems, mental deteriora-
tion, and seizures
 Chapter 10 Metabolic Disorders 403

SECTION III
A B
Figure 10-22 Creutzfeldt-Jakob disease. T2 (A) and diffusion-weighted images (B) showing marked hyperintense regions in the caudate
nuclei, putamina, thalami, and bilateral cortices. Dorsomedial and pulvinar thalamic nuclei lesions yield the hockey-stick sign.

Figure 10-23 Kearns-Sayre syndrome. Axial T2-weighted image

demonstrating diffuse high signal intensity regions within the corona
radiata and subcortical white matter. (From Lerman-Sagie T, Leshin-
sky-Silver E, Watemberg N, Luckman Y, Lev D. White matter involve-
ment in mitochondrial diseases. Mol Genet Metab 2005;84:127-136.)
404 Section III  Problem Solving: Disease Categories

BOX 10-21 Kearns-Sayre Syndrome (KSS) BOX 10-22 Cockayne Syndrome

and Chronic Progressive external
­Ophthalmoplegia (CPEO) nn Autosomal recessive
nn Disorder of DNA repair (like ataxia-telangiectasia,
nn Pearson syndrome (hypocellular anemia and pancre- Fanconi anemia)
atic exocrine deficiency) in infants may progress to nn Characteristic facies
Kearns-Sayre syndrome by school age nn Ultraviolet hypersensitivity, microcephaly, retinitis
nn KSS presents in the teenage years with progressive pigmentosa, cachexia
external ophthalmoplegia and pigmentary retinal
degeneration, cardiac blockade, cerebellar signs, and
sensorineural hearing loss
nn KSS shares many clinical and imaging features with
CPEO
nn Diffuse spongiform encephalopathy of the white
matter and less so the deep gray matter, brainstem,
and spinal cord (spongiform degeneration may also
occur in Leigh syndrome and Canavan disease)

A B
Figure 10-24 Infant with kernicterus. T1-weighted (A) and fluid-attenuated inversion recovery images (B) demonstrating symmetric regions
of hyperintensity of the globi pallidi.

PART IV: DIFFUSION Does the Lesion Show Facilitated Diffusion?

MELAS classically shows cortical and subcortical lesions
Diffusion-weighted images (DWI) can often separate T2 with T2 hyperintensity and facilitated diffusion despite
hyperintense lesions into those due to vasogenic edema clinical evidence suggestive for acute infarction (Figure
(facilitated diffusion) or cytotoxic edema (restricted dif- 10-27). The facilitated diffusion supports the defective neu-
fusion). Facilitated diffusion is hyperintense on DWI and ronal metabolism hypothesis, in which the mitochondrial
on ADC maps. Restricted diffusion is hyperintense on dysfunction causes anaerobic metabolism and neuronal
DWI and hypointense on ADC. DTI includes directional death from acidosis. Less commonly, MELAS lesions may
information about water diffusion, which is commonly show restricted diffusion due to failed energy metabolism
measured as FA. The DTI metric mean diffusivity is anal- according to the vascular hypothesis, where metabolic dam-
ogous to ADC. The demyelinating leukoencephalopa- age to the endothelium causes small-vessel occlusion and
thies cause increased mean diffusivity and decreased FA neuronal death. Chronic MELAS reveals worsening cerebral
on DTI, which may be more sensitive than conventional atrophy with areas of cortical laminar necrosis and cortical
imaging. The diffusion findings are summarized here and subcortical gliosis. Other diseases with ­facilitated dif-
and are also discussed under the individual diseases. fusion include Zellweger syndrome, adrenoleukodystrophy,
 Chapter 10 Metabolic Disorders 405

SECTION III
A B
Figure 10-25 Pantothenate kinase-associated neurodegeneration, formerly known as Hallervorden-Spatz syndrome. Coronal fluid-attenuated
inversion recovery (A) and axial T2-weighted images (B) showing classic hypointensity in the globus pallidus with anterior medial hyperintensity,
the eye-of-the-tiger sign.

BOX 10-23 Neurodegeneration with Brain Iron Accumulation (NBIA)/Pantothenate Kinase-Associated

Neurodegeneration (PKAN)/Hallervorden-Spatz Syndrome
nn NBIA is the preferred umbrella term for autosomal recessive disorders characterized by abnormal brain iron accumu-
lation, dystonia, and parkinsonism
nn NBIA includes Hallervorden-Spatz syndrome, pantothenate kinase 2 (PANK2) deficiency, hereditary aceruloplasmin-
emia, and neuroferritinopathy
nn Classic rapidly progressive disease presents before age 10 years with dystonia and upper motor neuron signs and
symptoms and intervening plateaus of stability
nn Atypical disease presents at age 13 years with dystonia, psychiatric and speech disturbances, and slow disease progres-
sion
nn All classic disease and one third of atypical disease have a PANK2 mutation on chromosome 20p13, which is respon-
sible for coenzyme A biosynthesis
nn PANK2 deficiency leads to accumulation of cystine-containing neurotoxins that result in edema, destruction, and iron
accumulation in normally iron-rich parts of the brain

Krabbe disease, mucopolysaccharidosis, Lowe syndrome, pattern of the diffusion restriction may vary depending
Alexander disease, and van der Knaap disease. Facilitated upon the acuity of the lesion.
diffusion in the leukoencephalopathies usually reflects Mixed vasogenic and cytotoxic lesions may be seen
slow progression with low-grade demyelination, tissue loss, in some diseases, such as MELAS. Other diseases such
and increased extracellular space (Box 10-25). as Pelizaeus-Merzbacher disease may have normal dif-
fusion imaging.
Does the Lesion Show Restricted Diffusion?
This finding is classic for infarction, particularly when PART V: SPECTROSCOPY
it involves both gray and white matter in a vascular ter-
ritory. Diffusion restriction may also be seen in meta- The specificity of conventional MRI may be improved
chromatic leukodystrophy, maple syrup urine disease, by proton MR spectroscopy, which allows in vivo semi-
Canavan disease, phenylketonuria, Wilson disease, quantitative measurement of brain metabolites. In
Cockayne syndrome, and glutaric aciduria type 1. The ­addition to helping to narrow the differential possibili-
restricted diffusion may represent more acute ischemic, ties, spectroscopy has an important role during man-
demyelinating, or vacuolating myelinopathy changes agement of these patients to follow disease progression
that mimic the cytotoxic edema diffusion pattern. The or treatment effects. Quantitative imaging ­biomarkers
406 Section III  Problem Solving: Disease Categories

A B
Signal intensity

ppm
C 4 2 0
Figure 10-26 Adult form of GM2 gangliosidosis B (Tay-Sachs disease) in a 47-year-old man. Sagittal (A) and axial T1-weighted images (B)
showing isolated cerebellar atrophy, which may be the only abnormality seen on conventional images. (Courtesy Yvonne W. Lui, MD, Montefiore
Medical Center, New York, NY.) C: Spectroscopy through the thalamus in another Tay-Sachs patient showing decreased N-acetylaspartate despite
normal-appearing supratentorial gray and white matter structures.

BOX 10-24 GM2 Gangliosidosis (Tay-Sachs Disease, Sandhoff Disease)

nn Heterogeneous group of lysosomal storage disorders
nn Autosomal recessive
nn Defective sphingolipid metabolism causes abnormal accumulation of gangliosidoses
nn Types B and O have discrete infantile, juvenile, and adult clinical forms
nn Earlier age of onset correlated with more rapid disease progression
nn Chronic adult form with neuropsychiatric disturbances that may mimic schizophrenia
nn Type B (Tay-Sachs disease) caused by hexosaminidase A deficiency on chromosome 15q23-q24
nn Type O (Sandhoff disease) caused by hexosaminidase A and B deficiency on chromosome 5q13; is less common but
clinically indistinguishable
nn Type AB is rare and has only an infantile form characterized by GM2 activator deficiency on chromosome 5
 Chapter 10 Metabolic Disorders 407

SECTION III
A B

C
Figure 10-27 Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke (MELAS). Computed tomography (A), fluid-attenuated
inversion recovery (B), and apparent diffusion coefficient (ADC) images (C) showing multiple bilateral cortical and subcortical stroke-like lesions
in a nonvascular distribution in the frontal and parietal lobes. The typical facilitated diffusion (high ADC signal) reflects vasogenic edema, com-
pared to the restricted diffusion and cytotoxic edema of acute infarction.

BOX 10-25 Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS)
nn Most common inherited mitochondrial abnormality
nn Primary neuronal oxidative metabolic disturbance
nn A3243G >> A8344G mitochondrial DNA mutations
nn Same mutation also causes mitochondrial epilepsy with ragged red fibers and chronic progressive external oph-
thalmoplegia
nn Stroke-like episodes before age 40 years, seizures, dementia, and lactic acidosis
nn Usually presents with gray and white matter lesions
nn Fluctuating stroke-like events in the cortical gray matter and subcortical white matter in a nonvascular distribution,
particularly in the temporal parietal and occipital lobes
nn May have isolated or symmetric involvement of the basal ganglia (similar to Leigh syndrome)
408 Section III  Problem Solving: Disease Categories

Table 10-4 C
 ommon Compounds Resolved by Clinical is caused by deficiency of the aspartoacyclase enzyme,
Magnetic Resonance Spectroscopy which causes the abnormal neurotoxic accumulation of
NAA in the brain and urine. Alexander disease, which
Major Compounds Parts per Million (ppm) can also present with macrocephaly and have early sub-
Myoinositol (mI) 3.56 cortical U-fiber involvement, is among the innumerable
diseases that show decreased NAA.
Choline (Cho) 3.22
Creatine (Cr) 3.03 Is NAA Decreased?
Glutamine/glutamate (Glx) 2.2–2.4 The combination of decreased NAA and increased Cho
is the most common and therefore least specific spec-
N-acetylaspartate (NAA) 2.02
troscopic pattern. Decreases in NAA reflect neuronal
Lactate (Lac) 1.33 loss and increases in Cho demyelination and inflam-
mation. This may be seen in both malignant (neo-
plastic) and nonneoplastic diseases. In addition to
the demyelinating leukodystrophies, other metabolic
using ­conventional and spectroscopic MRI will be disorders that may display this pattern include NCL,
important tools for novel genetic and stem cell therapies NBIA/PKAN2, MERRF, MELAS, Huntington, muco-
approaching clinical trials. polysaccharidosis, adrenoleukodystrophy, and GM2
The common metabolites demonstrated on routine gangliosidosis (Figure 10-2). MERRF and MELAS often
clinical MR spectroscopy are summarized in Table 10-4. show decreased NAA/Cr and NAA/Cho. Adrenoleuko-
NAA is a marker of neuronal density and viability that dystrophy may show spectroscopic abnormalities even
is decreased in most disease processes. Creatine (Cr) in areas that appear normal on T2-weighted and FA
and creatine phosphate are markers of cellular ener- maps. GM2 gangliosidosis may also reveal decreases in
getics and may be decreased due to higher metabolic NAA in the normal-appearing gray and white matter
demand and energy consumption. Choline (Cho) is structures (Figure 10-26).
a membrane turnover marker consisting of phosphor- Decreased NAA and decreased Cr may be seen in the
ylcholine and glycerophosphorylcholine, which may PKAN form of NBIA. Spectroscopy in these patients is
be increased by accelerated membrane synthesis and complicated by the high iron concentration, which may
myelination or breakdown. Lactate, which is normally broaden the calculated metabolite signals and alter the
not resolved, is elevated by anaerobic glycosis. Lipid is baseline values.
increased by cellular breakdown and necrosis. Gluta-
mate is an excitatory neurotransmitter, γ-aminobutyric Is Lactate Present?
acid (GABA) precursor, and intermediate of amino acid The mitochondrial disorders often present with lac-
metabolism. Myoinositol (mI) is found in glial cells and tic acidemia, variable encephalopathy, and myopathy.
may be increased by myelin breakdown products, glial They include Leigh syndrome, MERRF, MELAS, pyru-
proliferation, and gliosis. vate dehydrogenase complex deficiency, and respiratory
The leukodystrophies present three main spectro- chain complex enzyme deficiency. Increases in lactate
scopic metabolic patterns, which correlate with the are also common to many extramitochondrial neurode-
underlying pathophysiologic mechanism: generative disorders, as a result of increased reliance on
1. The hypomyelination disorders show normal or the glycolytic pathway due to abnormal oxidative phos-
near-normal spectra indicating relatively preserved phorylation.
membrane turnover and axonal density in the white Leigh syndrome shows increased lactate in the basal
matter despite deficient deposition of myelin. For ganglia, brainstem, and occipital cortex. This CNS lac-
example, Pelizaeus-Merzbacher syndrome may show tate elevation may occur in the setting of normal periph-
relatively normal spectra despite extensive white eral lactate. These lesions will also have increased Cho,
matter disease. thought to reflect demyelinating changes even in the
2. The demyelination disorders are characterized normal-appearing white matter. Increased lactate and
by increases in Cho, Cho/NAA, and Cho/Cr, and Cho and decreased NAA, although not particularly spe-
decreases in NAA. Cho increases are due to mem- cific, may help distinguish Leigh syndrome from sim-
brane turnover, accumulation of myelin breakdown ilar-appearing basal ganglia disorders, such as maple
products, and presence of inflammatory cells. NAA syrup urine disease and Wilson disease. Finding lactate
decreases result from loss of neuronal cells. in normal-appearing brain in both Leigh syndrome and
3. The vacuolization disorders show overall decreases MELAS can help distinguish these disorders from other
in Cho, Cr, and NAA due to rarefaction, cystic degen- mitochondrial disorders such as KSS.
eration, and neuronal and axonal loss. MLC is an Acute MELAS lesions will have increased lactate and
example. Cho and decreased NAA. These changes return to base-
line parallel with improved symptoms. Less marked
abnormalities can be found even in patients without
Is NAA Increased?
focal signal abnormalities on MRI. Increased CSF lac-
An increase in NAA is pathognomonic for Canavan dis- tate in the lateral ventricle has been correlated with the
ease because virtually all other diseases result in non- degree of chronic neurologic impairment. Lactate may
specific decreases in NAA (Figure 10-8). Canavan disease decrease with resolving symptoms.
 Chapter 10 Metabolic Disorders 409

Increased lactate may also be seen in maple syrup Cr. Patients with cognitive impairment have higher

SECTION III
urine disease, methylmalonic acidemia, glutaric acide- mI/Cr levels than those without cognitive impairment.
mia type II. At 3.56 ppm, nonketotic hyperglycemia shows an abnor-
mal peak that may be separated from the normal mI
Is Myoinositol Increased? peak by long echo spectroscopy.
Infantile NCL shows an early and persistent increase in At 2.42 ppm, a 3-hydroxy-isovalerate and/or 3-hydroxy-
mI, even after 4 years when there is a uniform decrease 3-methylglutarate specific peak may be seen in
in all main metabolites. Early increases in mI, Cho, and hydroxymethylglutaryl (HMG)-CoA lyase deficiency.
glutamine/glutamate (Glx) may reflect glial prolifera- At 0.9 to 1.0 ppm, a specific peak may be found during
tion, demyelination, and gliosis, and decreases in NAA decompensation of maple syrup urine disease.
neuronal loss and/or damage. Spectroscopy of the thala-
mus is thought to have better correlation with disease CONCLUSION
severity than spectroscopy of the white matter or cortex.
Lactate and lipids may be observed at 4 years. The metabolic diseases represent a diverse group of inher-
GM2 gangliosidosis (Tay-Sachs disease, Sandhoff dis- ited and acquired disorders, which are variably classified
ease) show increased mI reflecting gliosis due to toxic according to the genetic, phenotypic, histopathologic,
accumulation of GM2 gangliosides. or biochemical defect. Despite often nonspecific, over-
Alexander disease reveals a prominent increase lapping clinical, laboratory, and radiographic appear-
in mI due to intense gliosis. This is accompanied by ances, many disorders have distinctive features that can
decreased NAA, increased Cho, and increased lactate, be used to suggest a specific diagnosis or at least narrow
with abnormalities more obvious in the frontal lobes the differential possibilities to direct additional testing.
that correlate with the usual anteroposterior progres- Advanced imaging techniques, such as MR diffusion and
sion of disease. spectroscopy, offer additional tools to improve the sen-
Metachromatic leukodystrophy demonstrate an sitivity and characterization of the metabolic diseases.
increase in mI due to the increase of phosphatidylinosi- MR spectroscopy in particular adds valuable informa-
tol in myelin, particularly in patients with severe disease. tion through the in vivo measurement and tracking of
Lowe syndrome has increased mI that may be due to specific brain metabolites to aid the diagnosis, progno-
gliosis and possibly abnormal accumulation of phos- sis, and management of these patients.
phatidylinositol 4,5-biphosphate (Figure 10-7).
NBIA may show an increase in mI in the deep cere- Suggested Readings
bral white matter.
A novel gene containing a trinucleotide repeat that is expanded and unstable
on Huntington’s disease chromosomes. The Huntington’s Disease
Is Glx Increased? Collaborative Research Group. Cell. Mar 26 1993;72(6):971-983.
Huntington disease may show increases in mI and Glx in Adachi M, Kawanami T, Ohshima F, Hosoya T. MR findings of cerebral white
matter in Cockayne syndrome. Magn Reson Med Sci. Apr 2006;5(1):41-45.
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may also demonstrate asymmetric increases in lactate, AJNR Am J Neuroradiol. Sep 2000;21(8):1502-1509.
left greater than right, due to asymmetric basal ganglia Austin J, McAfee D, Armstrong D, O’Rourke M, Shearer L, Bachhawat B.
Abnormal sulphatase activities in two human diseases (metachromatic
activity during motor performance in right-handed leucodystrophy and gargoylism). Biochem J. Nov 1964;93(2):15C-17C.
subjects. Increased lactate in the occipital and frontal Austin JH. Metachromatic form of diffuse cerebral sclerosis. III. Significance
lobes may represent similar defective oxidative phos- of sulfatide and other lipid abnormalities in white matter and kidney.
Neurology. May 1960;10:470-483.
phorylation. The decreased NAA and increased lactate Autti T, Raininko R, Santavuori P, Vanhanen SL, Poutanen VP, Haltia M. MRI of
in the striatum correlate with symptom duration and neuronal ceroid lipofuscinosis. II. Postmortem MRI and histopathological
study of the brain in 16 cases of neuronal ceroid lipofuscinosis of juvenile
increased CAG repeat length. Cr may be a more sensi- or late infantile type. Neuroradiology. May 1997;39(5):371-377.
tive marker in juvenile and presymptomatic Huntington Aydin K, Bakir B, Tatli B, Terzibasioglu E, Ozmen M. Proton MR
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202-212.
 Chapter 11

Tumor
Marco Essig

INTRODUCTION
Unenhanced T1-weighted spin-echo (SE) or fast SE
The goals and requirements for brain tumor imaging are sequences are used to rule out intralesional bleeding
multiplex and involve making a diagnosis and a differ- and to visualize, for example, melanin, which is fre-
ential diagnosis, and accurate lesion grading is needed quently found in metastases from malignant melanoma
for tumor description. Imaging is also involved in the (Figure 11-1).
decision-making process for therapy and later for pre- T2-weighted fast SE sequences and fluid-attenuated
cise planning of surgical or radiotherapeutic interven- inversion recovery (FLAIR) are used to display the mar-
tions. After therapy, neuroimaging techniques have been gins of a tumor and its surrounding edema or a direct
shown to be mandatory for monitoring of disease and tumor infiltration. In the past years, FLAIR has mainly
possible therapy-related side effects. replaced proton density weighted sequences. In unco-
Because of the high tissue contrast and the noninvasive operative patients, motion-insensitive acquisition tech-
nature of the method, magnetic resonance imaging (MRI) niques should be used (Figure 11-2).
is accepted as the most sensitive method for characteriz- Contrast enhancement studies are mandatory in
ing brain tumors. Ruling out a brain tumor in patients the assessment of patients with cerebral tumors. The
with unspecific neurologic symptoms is one of the most standard dose used for MRI of the central nervous
common indications for neuroimaging using MRI. In the system is 0.1 mmol per kilogram of body weight,
past years it has become generally recognized that MRI although numerous studies have shown that lesion
would be the imaging study of choice in the evaluation of detection may be improved by use of higher doses and
intracranial tumors if availability and cost were not issues. dedicated sequences. Contrast-enhanced MRI helps
The classification of brain tumors still is controversial in distinguishing tumors from other pathologic pro-
and includes classification by location or by histology. cesses and enables optimal characterization of tumor
The most common classification is that of the World response to therapy, such as change in size, morphol-
Health Organization (WHO), which is summarized in ogy, and degree of contrast material enhancement
the WHO Blue Book series (latest edition 2007). (Figure 11-3).
Brain tumors are categorized into primary versus sec- The sequences after contrast administration should
ondary tumors based on the origin tissue and intraaxial include at least two planes of T1-weighted sequences
versus extraaxial tumors based on origin of growth. The and, if possible, a volumetric sequence (e.g., three-
most common primary intraaxial tumors are neuroepi- dimensional gradient-recalled echo) to allow for recon-
thelial tumors, which include astrocytomas, oligoden- struction in different planes and volumetric assessment
drogliomas, mixed gliomas, and other neuronal–glial of the lesions.
tumors. Glioblastoma multiforme is the most common In the past few years, a number of advanced, non-
brain tumor. Meningiomas are the most common pri- enhanced, and contrast-enhanced MRI techniques
mary extraaxial tumors, accounting for about 20% of all have been developed that provide new insights into
brain tumors. In adults, secondary metastatic brain lesions the pathophysiology of brain tumors, mainly gliomas.
from systemic cancer far outnumber primary tumors. They include MR spectroscopy (MRS), perfusion MRI,
dynamic contrast-enhanced MRI, and diffusion tensor
KEY QUESTIONS FOR PROBLEM MRI. These techniques may help to answer the second
SOLVING IN BRAIN TUMOR question: Is the lesion a tumor?
If the presence of a tumor is determined, the best
IMAGING
possible differential diagnosis should be given. In addi-
For the radiologic imaging of cerebral lesions, a few key tion to the actual radiologic appearance of the tumor,
questions have to be answered in order to solve prob- including the characterization obtained with different
lems in brain tumor imaging. modalities (e.g., MRI, computed tomography [CT], and
1. Is a lesion present? positron emission tomography), the following param-
2. Is the lesion a tumor? eters that help with the differential diagnosis should be
3. Are any complications present that need an immedi- considered (Table 11-2 and Figure 11-4):
ate intervention? nn Age of the patient (most important in pediatric
4. What is the most likely differential diagnosis? patients)
The first question can be easily addressed by using an nn Relevant clinical history
appropriate brain tumor imaging protocol in MRI and nn Previous available imaging studies and/or clinical and
should include the following sequences (Table 11-1): radiologic follow-up

412
 Chapter 11 Tumor 413

Table 11-1 Proposed MRI Protocol for Brain Tumor Imaging Including Advance Techniques

SECTION III
Acquisition
Sequence TR Range (ms) TE Range (ms) Orientation Time (min)
T1 SE 500–700 10–12 Tra/Cor 2–4
T2 FSE 3,000–5,000 80–100 Tra/Cor 2–4
FLAIR 9,000–9,500 100–110 Tra/Cor 3–5
Administration of 0.1 mmol Gadolinium Contrast Agent per Kilogram of Body Weight
T1 SE 500–700 10–12 Tra/Cor 2–4
T1 3D GRE 8–15 5–7 Isotropic 3–5
Alternative Sequences
DWI/DTI 2,900 90 Tra 1.30
PWI 1,400 32 Tra 1.40
MRS Variable Variable Up to 12
T1 Dynamic MRI (DCE-MRI) 2.03 0.95 Tra 3–5

3D GRE, Three-dimensional gradient-recalled echo; Cor, coronal; DTI, diffusion tensor imaging; DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion
recovery; FSE, fast spin echo; MRS, magnetic resonance spectroscopy; PWI, perfusion-weighted imaging; SE, spin echo; Tra, transverse.

A B
Figure 11-1 A: Unenhanced T1 spin echo on a 3-T system in a patient with melanoma. The cerebral lesion presented with increased signal
intensity representing melanin or blood products (methemoglobin) in the metastatic lesion. B: On susceptibility-weighted magnetic resonance
imaging, both melanin and blood products may cause susceptibility artifacts, which clearly present the size and origin of the lesion.
414 Section III  Problem Solving: Disease Categories

products or have a high protein content that does not

allow for optimal suppression of the cystic fluid on
FLAIR imaging. Therefore, these regions are hyperin-
tense to normal CSF on FLAIR, with increasing signal
parallel to increasing protein content. Fluid debris
intensity levels are a pathognomonic sign of cystic tis-
sue and often are quite striking and frequent in cases
of cystic tumors.
Hemorrhage is uniquely depicted by MRI because
of the paramagnetic properties of many of the blood
products. The appearance of those products depends
on their age and amount. On MRI, old hemorrhage is
easily distinguished from other fluid (e.g., CSF) because
of the paramagnetic properties of methemoglobin, a
marker of subacute to chronic intracranial hemorrhage.
However, the tendency of certain primary intracranial
neoplasms to bleed (e.g., glioblastoma, ependymoma,
oligodendroglioma) and metastases (e.g., melanoma,
lung carcinoma, renal cell carcinoma, choriocarcinoma)
can be of great importance for the differential diagnosis
and increases the sensitivity (Figures 11-1 and 11-4).
Although it is important to discover hemorrhage, it
Figure 11-2 BLADE FLAIR acquisition for therapy planning in an also is critical to define its etiology. CT is of limited
uncooperative patient with oligoastrocytoma grade III. Note the few value for this purpose. The signal intensity pattern of
artifacts using the BLADE technique. The tumor tissue appears bright intratumoral hemorrhage differs from that of benign
on T2 and BLADE FLAIR with infiltration of the cortical U fibers, the intracranial hematoma. Signal intensity presents as
cortical gray matter, and the corpus callosum. Infiltration of cortical
and periventricular tissue is best seen on FLAIR images. heterogeneous in tumor bleeds but is more homoge-
neous in parenchymal hemorrhage. The appearance of
blood also is different between the entities. Blood may
not evolve as rapidly if it is within tumor tissue, pre-
PRACTICAL ASPECTS OF MRI IN senting different stages of blood, in comparison with
the fast evolution of benign hematomas. Some tumors
BRAIN TUMORS
contain tissue that may mimic a hematoma. The most
Using a standard MRI protocol for cerebral neoplasms important tumors are metastases from melanoma. The
as provided in Table 11-1 allows high-resolution imag- melanin pigments substantially shorten the T1 relax-
ing and characterization of lesions. Most tumors present ation time, and the tumors appear hyperintense on
low intensity on T1-weighted images and high intensity unenhanced T1 sequences. The effect on T2 relaxation
on T2-weighted images (Figure 11-5). is small, and no signal changes are seen in most cases.
More recently, FLAIR imaging, a T2-weighted However, melanoma metastases are commonly both
sequence with suppression of the signal intensity of hemorrhagic and melanotic, so imaging is less specific
cerebrospinal fluid (CSF) or any fluid with the T1 of in many subjects.
CSF, has become a part of most brain imaging proto- Calcifications can be depicted only if they are
cols. Initially used for imaging white matter changes, extensive or with the use of susceptibility weighted
FLAIR has become a standard sequence in brain tumor MRI sequences. Rim-shaped calcifications, as in cystic
imaging protocols. It can be particularly useful in lesions, may mimic chronic hemorrhage in the hemo-
proving the cystic content of a lesion or in the delin- siderin stage (Figure 11-7).
eation of tumor from CSF containing areas, for exam- The enhancement seen in brain tumors is based
ple, the ventricles, surgical defects, or cystic tumor on a disrupted blood–brain barrier (BBB), which can
parts. A lesion that is exactly isointense to CSF on be compromised by neovascularization and direct
T1-weighted, T2-weighted, and FLAIR images can con- tumoral damage. Because nonneoplastic astrocytes are
fidently be stated as being cystic, a pattern followed required to induce BBB features of cerebral endothe-
by arachnoid cysts and cysts associated with extraaxial lial cells, it is conceivable that malignant variants of
masses (Figure 11-6). these cells have lost this ability due to dedifferentia-
In patients with cerebral gliomas, FLAIR was found tion. Alternatively, glioma cells might actively degrade
to be superior to conventional imaging in tumor previously intact BBB tight junctions. Although the
delineation and in the differentiation between tumor integrity of the barrier within the tumor often is com-
and edema. Due to the suppression of the CSF sig- promised, the alteration in permeability is variable and
nal and a reduced gray-to-white matter contrast on dependent on the tumor type and size. Moreover, it is
the FLAIR images, periventricular, cortical, and cal- extremely heterogeneous in a given lesion. Although
losal lesions could be better detected and delineated. the BBB frequently is leaky in the center of malignant
Unfortunately for the radiologist, tumor cysts and brain tumors, the well-vascularized, actively proliferat-
cystic necrosis within neoplasms often contain blood ing edge of the tumor, in the brain adjacent to tumor
 Chapter 11 Tumor 415

SECTION III
A B

C D
Figure 11-3 Contrast-enhanced (0.1 mmol per kilogram of body weight) magnetic resonance imaging of a patient with recurrent malignant
glioma (World Health Organization grade IV). T2-weighted (A) and FLAIR (B) images showing a large area of T2 hyperintensity with small foci of
lower signal representing the high cellular density tumor areas. C, D: These tumor areas show pronounced contrast media enhancement with the
typical pattern of high-grade gliomas. The frontal lesion can be considered tumor spread via the meninges or a second malignant tumor change
in a large area of suspected low-grade tumor tissue.
416 Section III  Problem Solving: Disease Categories

area, has been shown to have variable and complex of enhancement and the volume of the peritumoral
barrier integrity (Figure 11-8). edema could be expected. Holodny et al studied this
In secondary metastatic intraaxial tumors and extra- correlation in malignant gliomas representative of pri-
axial tumors, the vessels are different from normal cere- mary intraaxial tumors and meningiomas representative
bral vasculature and have no or strongly disturbed BBB. of extraaxial tumors. In their study, no correlation was
Those entities normally have a strong enhancement pat- found for meningiomas, which proved that the menin-
tern, presenting the whole tumor as an enhancing mass gioma vessels have no BBB or no effect on the BBB in
(Figure 11-9). the surrounding brain tissue. A strong correlation was
Because brain edema is also thought to be due to found for malignant gliomas, which offers evidence that
breakdown of the BBB, a correlation between the degree the BBB defect is directly related to both the degree of
lesion enhancement and the amount of edema, and that
the two interfere with each other. The interference may
influence both conventional contrast-enhanced MRI as
Table 11-2 K
 ey Imaging Characteristics for Differential well as some of the flow-dependent functional imaging
Diagnosis/Problem Solving techniques.
Location of lesion Supratentorial versus infratentorial
Problem Solving: Common
Intraaxial versus extraaxial location Intraaxial Tumors
Single lesion versus multiple lesions
The most common intraaxial lesions to be differentiated
Associated findings Edema and/or tumor infiltration are the following:
nn Astrocytic tumors
Mass effect
nn Lymphomas
Signal characteristics of lesions that are helpful in the differen- nn Metastases
tial diagnosis
nn Abscesses
High signal on Metastases of melanoma nn Tumefactive demyelinating lesions
­unenhanced T1 (Figure 11-1)
The main problem to be solved is the differen-
Subacute bleeding/hemorrhage, tiation between primary and secondary tumors,
e.g., in oligodendroglioma the grading of primary intraaxial tumors, and the
(Figure 11-4)
­therapeutically important difference between gliomas
Signal on T2 High = low cellularity and lymphomas.
Low = high cellularity A common problem with intraaxial tumors is that
cerebral metastases can mimic cerebral tumors with
Low signal on both Calcifications
T1 and T2
isointense to hypointense signal on T1-weighted imaging
and hyperintensity on T2-weighted imaging. ­Intensive

A B
Figure 11-4 A: Magnetic resonance image of a patient with a grade II oligodendroglioma showing the typical patterns of streaky high signal on
unenhanced T1 representing blood products. B: After contrast media, only subtle signs of enhancement could be detected.
 Chapter 11 Tumor 417

SECTION III
A B
Figure 11-5 T2-weighted (A) and T1-weighted (B) images of a patient with low-grade astrocytoma showing the typical signal changes of cere-
bral tumors with high intensity on T2. In this case, infiltration into the corpus callosum and low signal on T1 are clearly seen.

edema is present in large lesions but frequently is absent Problem Solving: Differentiating
in small metastatic lesions. Recurrent Tumor from Therapeutic-
Astrocytic tumors account for up to 80% of glial neo- Induced Changes
plasms and refer to diffuse infiltrating tumors originat-
ing from glial cells. The tumor border on both imaging The differentiation of recurrent tumor from therapeutic-
and histology is ill defined with an infiltration that pri- induced changes is another common problem in brain
marily does not obey the anatomic cerebral structures. tumor imaging.
The tumors often distort the structures with the appear- After radiation or chemotherapy, BBB breakdown
ance of cysts. can occur and mimic tumor recurrence. Differentiation
Under the recent WHO classification of primary between these two entities often is not possible using
intracranial tumors, grade I to grade IV tumors can be standard MRI techniques. MRS has been shown to be
differentiated. useful in identifying tumoral tissue by the presence of
Grade I or pilocytic tumors are normally present in choline and, in high-grade tumors, lactate. Choline,
children and young adults. The main problem is the dif- which is a marker of membrane turnover, is normally
ferentiation between low-grade (grade II) and high-grade not present in necrosis (Figure 11-13).
or malignant gliomas (grades III–IV). Based on imaging
and enhancement characteristics, this differentiation is Problem Solving: Common
not possible in about 20% to 30% of cases. In these cases, Extraaxial Tumors
a more sophisticated imaging strategy that includes MRS
and perfusion MRI is required (Figure 11-10). Extraaxial masses arise from tissue at the surface of the
For enhancing lesions, gliomas and lymphomas brain and include lesions that arise from the ventricles
often cannot be differentiated, especially if the lesions or ependyma (Figure 11-14). They tend to displace the
present with a butterfly appearance. brain structures and may cause a CSF cleft. They pre-
Besides the clinical history (e.g., immunocompro- serve the normal cerebral structures and the gray–white
mise), functional imaging tools may help in the differ- ­matter junctions (Figure 11-14).
ential diagnostic process. Whereas astrocytomas often The main extraaxial lesions are meningiomas, cho-
present with high values of perfusion and a high ratio of roids plexus tumors, tumors of the sella, and cerebral
choline to N-acetylaspartate (NAA) (Figure 11-11), lym- nerve sheath tumors. Metastases can originate from
phomas normally present with substantially lower per- extraaxial tissue.
fusion values. The extent of edema is normally less than Common problems with extraaxial tumors are dif-
observed in gliomas or metastases. The enhancement ferentiation between meningiomas and nerve sheath
is intensive (Figure 11-12), and detection of a strong tumors (e.g., schwannomas) and differentiation of cys-
enhancement along the perivascular spaces is typical tic lesions. Clinically, the description of the mass effect
for lymphomas, with sarcoidosis the only differential in extraaxial lesions and the influence of neuronal func-
­diagnosis. tions are of importance.
418 Section III  Problem Solving: Disease Categories

A B

C D
Figure 11-6 Magnetic resonance imaging of a patient with anaplastic (grade III) astrocytoma. On unenhanced T1-weighted (A) and T2-weighted
(B) images, one can speculate about an infiltration of the corpus callosum. However, the best visualization of the infiltration can be achieved by
using FLAIR acquisition. Due to the high signal-to-noise ratio and the suppression of cerebrospinal fluid, the tumor tissue can be nicely seen (C).
In another case (D), infiltration in the genu of the corpus callosum can be appreciated.
 Chapter 11 Tumor 419

SECTION III
A B C

D E
Figure 11-7 Computed tomography (CT) (A, B) and magnetic resonance imaging (C–E) in a patient with multiple cerebral lesions. CT shows
a large cystic lesion in the right parietal lobe with calcifications and faint enhancement. T1 unenhanced spin echo (SE) showed a faint high signal
indicating blood byproducts and areas of low signal that are also present on T2-weighted fast SE sequences. The latter are seen in concordance to
the calcifications on CT. The solid-appearing left frontal lesion shows no enhancement and no calcification. Enhancement was visible only in the
right-sided lesion. The signal characteristics combined with knowledge of calcification favor the diagnosis of an oligodendroglioma, which was
confirmed at histology.
420 Section III  Problem Solving: Disease Categories

A B

C
Figure 11-8 Typical enhancement pattern in a patient with malignant glioma. The more solid parts appear darker in T2 (A) and FLAIR (B) and
present with a strong enhancement (C). The surrounding lower tumor grade tissue still has an intact blood–brain barrier.
 Chapter 11 Tumor 421

SECTION III
Figure 11-9 Typical rim-shaped enhancement in a patient with
metastatic disease. Metastases can show any type of enhancement;
however, the most common is the rim shape with substantial sur-
rounding edema.

A B
Figure 11-10 Perfusion magnetic resonance imaging (MRI) of lesions with unknown histology. A: The lesions showed hyperintensity on T2,
a focus of enhancement not easily differentiated from a vascular structure. B: Perfusion MRI, displayed is the regional cerebral blood flow map,
demonstrating a lesion with high perfusion, which can be classified as a high-grade glioma. Histology confirmed a grade IV astrocytoma or glio-
blastoma multiforme.
422 Section III  Problem Solving: Disease Categories

Figure 11-11 Choline to N-acetylaspartate (NAA) ratio color

coded from magnetic resonance CSI data. Note the hot spot in red in
the center of the tumor representing a ratio of high choline and low
NAA, which is typical for a high-grade astrocytic tumor.

Figure 11-12 Contrast-enhanced T1 and arterial spin labeling perfusion magnetic resonance imaging in a patient with cerebral lymphoma.
Although the tumor presents with avid contrast enhancement, the perfusion values are low, which allows differentiation from the normally highly
perfused primary intraaxial tumors and central nervous system lymphoma.
 Chapter 11 Tumor 423

SECTION III
Figure 11-13 Tumor necrosis and recurrent tumor in the same patient after radiation therapy of an anaplastic (grade III) astrocytoma. The
patient presented 9 months after radiation with multiple new enhancing, partially cystic lesions, all suspicious for tumor progression. Magnetic
resonance spectroscopy was used for further differentiation. The lesion adjacent to the lateral ventricle showed no choline and was histologically
proven radionecrosis, whereas the lesion on the left temporal lobe presented a typical tumor spectrum and was confirmed as recurrent tumor.
Cho, Choline; NAA, N-acetylaspartate.

A B
Figure 11-14 Typical magnetic resonance image of a supratentorial extraaxial lesion that can clearly be identified radiologically as a
meningeoma. Extraaxial location with slight displacement of the adjacent cerebral tissue and homogeneous enhancement.

Meningiomas versus Schwannomas

Arachnoid cysts contain CSF with normal protein con-
Compared to schwannomas, meningiomas tend to tent and therefore have identical signal as the ventricles
show calcifications, especially if they are large, have a in all sequences, including FLAIR (Figure 11-16).
periosteal bony reaction/exostosis, and have broader Epidermoid cysts usually are located at the skull base
contact with the skull with a typical dural tail sign in the and may have CSF-like signal in conventional imaging
majority of cases (Figure 11-15). sequences. However, in most cases they appear hyper-
A common problem that is easy to solve is the dif- intense on FLAIR. The surface may be irregular and can
ferentiation between arachnoidal cysts and epidermoid show calcification on CT. The diagnostic key is use of
cysts (Figure 11-16). Although the differential diagno- diffusion-weighted imaging sequences in which the
sis is difficult based on CT alone, MRI with diffusion- lesion appears very bright due to restricted diffusion
weighted imaging sequences is the key diagnostic step. (Figure 11-17).
424 Section III  Problem Solving: Disease Categories

A B

C D
Figure 11-15 Skull base lesion in computed tomography (A) and axial magnetic resonance imaging (B) showing some bone reaction and
strong contrast enhancement extending into the inner auditory canal (C). The diagnosis of meningioma is based on the dural tail sign, which is
most obvious in the coronal orientation (C, D).
 Chapter 11 Tumor 425

SECTION III
Figure 11-16 Uncomplicated arachnoid cyst of the temporal lobe as an incidental findings in a young volunteer. Note the cerebrospinal fluid
(CSF)-like signal in all sequences. A pitfall, which can be a helpful sign in the presence of CSF, is pulsation artifact within the cyst on FLAIR imaging.

Figure 11-17 Epidermoid cyst in typical location and high signal on diffusion-weighted imaging sequences. This helps to differentiate the
lesion from an arachnoid cyst (see Figure 11-16). Note the intermediate signal on FLAIR imaging.

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 chapter 12

Brain Trauma
Alessandro Cianfoni and Cesare Colosimo

HEAD TRAUMA
used to define which patients with head trauma and
Who Needs to Be Imaged? When GCS score = 15 require a head CT scan. Although there is
to Best Image? What Are the Most strong evidence that clinical factors can predict imaging
abnormalities and the need for intervention in adults,
Optimal Imaging Techniques?
there is no such evidence for mild traumatic brain injury
Traumatic injuries of the brain and spinal cord are a in children. Given the difficulty in assessment of these
leading cause of death and permanent disability among patients, the threshold for performing CT is lower. Other
individuals younger than 50 years, accounting for 15% risk groups include elderly people, intoxicated individu-
to 20% of deaths in the age group comprising individu- als, and patients with a coagulopathy (history of bleeding,
als aged 5 to 35 years. Clinical management of the head- clotting disorder, current treatment with anticoagulants).
injured patient begins with assessment of the degree of These concepts are summarized on Table 12-2. It is safe
patient risk according to the symptoms of intracranial to state that, whenever in doubt, head imaging should be
injury. This assessment then can be used as a guide to obtained, even in patients with mild head injury.
further treatment.
What Are the Most Optimal Imaging Techniques
What Are the Indications for Imaging and Protocols in Head Trauma?
in Head Trauma? CT scanning is the primary imaging technique for acute
Debate continues in the medical literature about which brain injury. It provides rapid information and is part of
patients with head trauma need to be imaged in the a general trauma workup in emergency situations.
emergency situation. Various authors note indications Head CT should be performed in sequential axial,
for imaging of the head in patients who sustained head rather than helical, mode to avoid artifacts that might
trauma. The indications are listed in Table 12-1 and affect the quality of the images for brain parenchyma
include Glasgow Coma Scale (GCS) score <15; clinical evaluation. Noncontrast CT is fast and accurate for the
signs of basal skull fracture or depressed skull fracture; detection of intracranial hemorrhage, mass effect and
all penetrating head injuries; anisocoria or fixed and edema (including brain herniation), skull fractures, dis-
dilated pupils; neurologic deficit, including focal motor placed bone fragments, foreign bodies, and intracranial
paralysis, cranial nerve deficit, and abnormal Babinski air. CT scan with intravenous contrast usually is unnec-
reflex; loss of consciousness for more than 5 minutes; essary. Furthermore, contrast infusion imaging may
and antegrade amnesia. obscure some pathology in the acute setting, most nota-
The role of computed tomography (CT) in severely bly subarachnoid hemorrhage. In severely head-injured
head-injured patients is well documented. The indica- patients, CT should be performed as soon as possible
tions for CT in patients with minor head injury are less to assess the possible need for surgical intervention and
clear than for those with severe head injury. for intracranial pressure (ICP) management. In the fol-
lowing hours and days, critically injured patients can
What Are the Indications for Imaging in Minor be monitored within the scanner with relative ease.
Head Trauma? Most trauma centers now use multidetector computed
Minor head injury usually is defined as a blunt injury to
the head, after which the patient may briefly lose con-
sciousness, may have short posttraumatic amnesia, but Table 12-1 Indications for Head Computed
have a normal mental status at presentation (GCS score Tomographic Imaging in Patients with
= 15). In patients with mild traumatic brain injury who Head Trauma
present to the hospital with GCS = 15, the estimated Glasgow Coma Scale <15
prevalence of intracranial CT scan abnormalities is as Loss of consciousness >5 minutes
high as 5%. Approximately 0.1% to 1% of all patients Antegrade amnesia
with mild traumatic brain injury present to the emer- Penetrating head injury
gency room require neurosurgical intervention. Miller et Clinical signs of skull base fracture
al. determined that four simple clinical variables—severe Clinical evidence of depressed skull fracture
Anisocoria or fixed dilated pupils
headache, nausea, vomiting (more than one episode),
Neurologic deficit (central nervous system, cranial nerves)
and skull depression on physical examination—can be

427
428 Section III  Problem Solving: Disease Categories

tomography (MDCT). This technology provides iso- deposits. MRI also is useful in cases with unexplained
tropic datasets that can be used for high-resolution findings on CT scanning or when CT cannot explain the
three-dimensional (3D) postprocessing to better show current clinical findings, such as patients with a focal neu-
fractures of the skull vault, maxillofacial region, and rologic deficit or prolonged period of unconsciousness.
even the petrous bones and skull base. In patients with MRI is superior to CT in visualizing posterior fossa or
craniocerebral trauma, CT images of the head are best brainstem lesions and in delineating vascular or diffuse
viewed in three window/level (W/L) settings as follows axonal injuries. The most useful MR pulse sequences for
(Figure 12-1): brain parenchyma setting (W 80–120 head trauma imaging are the spin-echo (SE) T1-weighted
Hounsfield units [HU], L 30–50 HU); bone setting to image (T1-WI), fluid-attenuated inversion recovery
identify skull fractures (W 2,000–4,000 HU, L 500 HU); (FLAIR) image, T2-weighted image (T2-WI), gradient-
and intermediate setting for detection of thin layer of recalled echo (GRE) T2*-WI, and, in the acute or early
subdural or epidural blood against the dense calvarium subacute stage, the diffusion-weighted image (DWI).
(W 150–300 HU, L 50–100 HU).
In order to promptly diagnose patients with blunt What Is the Role of Skull Plain X-Ray Films
vascular injury who are at risk for major strokes, some in Problem Solving?
authors suggest the routine use of computed tomo- Plain films represent a valid technique for diagnosing
graphic angiography (CTA) to simultaneously examine skull vault fractures. However, skull fractures can occur
the cervical spine and cervical arterial system during without associated loss of consciousness; conversely,
assessment of acute multitrauma patients. severe intracranial pathology can be present even in the
For the detection of subacute and delayed sequelae absence of a fractured skull. Therefore, the diagnostic
of head trauma, magnetic resonance imaging (MRI) is yield of plain films is low because of the poor correla-
more sensitive than CT for evaluating the full extent of tion between skull fractures and intracranial injury. Plain
brain injury and has the ability to identify posttraumatic x-ray films of the skull contribute little or no additional
encephalomalacia, reactive gliosis, and hemosiderin information in the clinical management of the acute head
trauma patient. In most major trauma centers, plain x-ray
films of the skull have been supplanted by CT scanning.
Table 12-2 Indications for Head Computed
Tomographic Imaging in Mild Head Trauma
(Glasgow Coma Scale=15) ACUTE ADMISSION IMAGING
Severe headache Head
Nausea and vomiting (>1 episode)
Clinical suspicion of depressed skull fracture or large scalp hema- What Is the Role of Imaging in the Acute Phase?
toma obscuring clinical examination Acute head trauma imaging, obtained as soon as pos-
Children, especially <2 years (keep radiation dose as low as pos- sible after resuscitation, is directed at evaluating diffuse
sible) and focal lesions, identifying lesions that need urgent
Elderly patients surgical intervention, and assessing the mass effect
Intoxicated patients
caused by the primary lesions and by the early develop-
Coagulopathic or anticoagulated patients
ment of brain edema.

A B C
Figure 12-1 Window settings for noncontrast head computed tomography (CT) in trauma. Head CT images should be evaluated with brain
parenchyma window settings (A) to appreciate good gray–white matter contrast, sensitive to intraaxial blood and edema; with bone window
settings (B) to visualize skull fractures (arrow); and with intermediate window settings (C) to enhance visualization of small extraaxial blood
collection adjacent to the inner surface of the calvarium. Note better visualization of this small epidural hematoma (arrowheads) in C than in A.
 Chapter 12 Brain Trauma 429

Which Are the Possible Traumatic Lesions Problem Solving: Is There an Extraaxial

SECTION III
to Look for in the Acute Stage? Collection? How to Differentiate Between
Problem Solving: Are There Primary Versus Different Types of Extraaxial Collections?
Secondary Lesions? Epidural Hematoma
Head trauma can cause primary and secondary lesions An EDH is an extracerebral collection of blood within
(Table 12-3). Primary lesions are directly and immedi- the epidural space, which is the potential space between
ately caused by the impact, the penetrating injury, or the the inner table of the skull and the firmly adherent outer
deceleration forces. Secondary injuries are determined layer of the dura mater. An EDH can be of arterial (90%)
by the ensuing rise of ICP, edema, brain herniation, or venous (10%) origin. Arterial EDH is typically found
vascular damage and compression, embolism, hypoten- at the coup site and is associated with a skull fracture,
sion, and hypoxia. most commonly of the squamosal portion of the tem-
poral bone (Figure 12-3), due to injury of one or more
Primary Lesions branches of the meningeal arteries. Arterial EDH tends
Skull Fractures to enlarge. Hyperacute EDH can appear heterogeneous
Skull fractures are often present in severe craniocere- on CT, with areas of high density representing clotted
bral trauma. However, about 20% of patients with blood and hypointense lucent swirls indicating blood
fatal head injuries do not have a skull fracture, so the that has not yet clotted (Figure 12-3). These features
absence of a skull fracture does not necessarily predict indicate the greatest potential for rapid enlargement. As
better clinical status. On the other hand, fractures can the EDH matures, hyperdensity distribution becomes
also be associated with mild clinical conditions. The more homogeneous. Venous EDH is due to injury to the
diagnosis of a skull fracture requires visualization of sphenoparietal sinus, transverse sinus, or superior sagit-
the CT images with a bone window setting and can be tal sinus and is typically found along the anterior wall
further aided by 3D surface-shaded volume-rendering of the middle cranial fossa, at the vertex, or against the
images (Figure 12-2). Skull fractures can be linear, occipital bone along the transverse sinus (Figure 12-4).
complex, or comminute. Depending on their location, The venous EDH seldom enlarges because of the con-
they can cause vascular lacerations resulting in arte- taining force of the dural adhesion to the inner table of
rial or venous epidural hematomas (EDHs) that have the calvarium.
to be actively searched using various window settings CT is the preferred imaging technique because of its
and possibly multiplanar reformatting. An important rapid accessibility and because it shows both the hemor-
feature of a fracture to define is whether it is depressed rhage and the causative skull fracture. Due to the attach-
(Figure 12-2). A depressed skull fracture is important ment of the dura to the calvarium, EDH has a typical
clinically because it may cause injury of the brain focal biconvex configuration that may cross dural folds,
parenchyma, may be associated with penetration of the such as falx and tentorium, but not sutures, where the
brain by foreign bodies, and may compress the brain dura is even more firmly anchored. A vertex EDH may
parenchyma. As a rule of thumb, if the depression not be seen on axial CT images unless it has a significant
of the fracture’s margins is equal or greater than the mass effect or it is imaged on reformatted coronal or
calvarium thickness, surgery to reduce the fracture is sagittal images.
considered. Special attention should be directed to the
extension of the fracture line to the skull base because Subdural Hematoma
of the possible risks of cerebrospinal fluid (CSF) fis- A subdural hematoma (SDH) is an extracerebral collec-
tula and vascular damage. The presence of pneumo- tion of blood within the subdural space, which is the
cephalus implies that the fracture may be connected to virtual space between the dura mater and the arach-
a penetrating injury, the paranasal sinuses, or mastoid noid membrane. It is due to tearing of bridging veins
air cells and represents a risk factor for CSF fistula and (Figure 12-5) as they pierce the outer arachnoid mem-
intracranial infection. In penetrating injuries, a detailed brane. There is no consistent relationship with skull frac-
description of the size and location of intracranial bony tures. SDH does cross suture lines but is limited by falx
fragments and foreign bodies might be helpful to the and tentorium. Most SDHs are ipsilateral to the site of
neurosurgeon. trauma, but approximately one third occur contralateral
to the site of injury. SDHs are also seen within the inter-
hemispheric fissure, along the falx, and along the tento-
Table 12-3 Primary and Secondary Brain Traumatic rium. Due to the absence of attachment between the dura
Lesions mater and the outer arachnoid membrane, SDH is seen,
Primary Lesions Secondary Lesions
differently from EDH, as a crescent-shaped fluid collec-
tion lying between the brain and the inner skull table
Skull fracture Brain swelling (hyperemia and (Figure 12-5). Due to the anatomy of the subdural space,
Epidural hematoma edema) a considerable volume of blood can be seen as a rela-
Subdural hematoma Brain herniation
Subarachnoid and intraven- Vascular complications tively thin SDH and still cause significant mass effect on
tricular hemorrhage Cerebrospinal fluid fistula and the brain. On CT the density of an SDH depends on the
Cortical contusion pneumocephalus interval between the last major episode of bleeding and
Brain hematoma the time of examination. Acute SDH is seen as a dense,
Diffuse axonal injury
Brainstem contusion
crescent-shaped collection. Mixed density of an acute
SDH might indicate very recent or active bleeding that
430 Section III  Problem Solving: Disease Categories

A B C

D E F
Figure 12-2 Computed tomography of skull fractures. A–C: Linear lucency, consistent with a fracture, of the left temporal squama (arrow in A),
better appreciated in its entire course on three-dimensional volume-rendering reformatted images (arrowheads in B). C: This fracture is associated
with an epidural hematoma visible with intermediate windowing. D: Three-dimensional views are especially useful in case of complex and com-
minuted fractures, as in this case. E, F: Multiple skull and skull base fractures. Depressed fractures (arrow in E and F) might represent a surgical
indication, whereas fractures causing pneumocephalus, such as these ethmoid plate comminuted fractures (arrowheads in F), are a risk factor for
cerebrospinal fluid fistula and intracranial infection.
 Chapter 12 Brain Trauma 431

SECTION III
A B

C D
Figure 12-3 A, B: Large acute epidural hematoma causing mass effect and subfalcine herniation is associated with a fracture of the right tempo-
ral squama (arrows in B), likely involving a branch of the middle meningeal artery. C, D: Two different acute epidural hematomas characterized by
heterogeneous density. The hypodense areas (arrowheads) are represented by hyperacute and nonclotted components, suggesting active bleeding
and rapid growth potential.
432 Section III  Problem Solving: Disease Categories

A B

C D
Figure 12-4 Venous epidural hematomas usually are self-limited and commonly are found in the anterior portion of the middle cranial fossa
(arrowhead in A), adjacent to the superior sagittal sinus (arrowheads in B) or the transverse sinuses. Hematoma is indicated by arrowhead in C. Trans-
verse sinus is indicated by arrow in C. These hematomas can be associated with skull fractures involving the dural sinuses (arrow in D).
 Chapter 12 Brain Trauma 433

SECTION III
A B

C D
Figure 12-5 Bridging veins and subdural hematomas. Bridging veins drain the brain surfaces, traverse the subarachnoid space, pierce the arach-
noid, and connect to larger venous collector draining into the dural sinuses. They are best visualized in their subarachnoid course on postcontrast
T1-weighted images (arrow in A and B). Tearing of bridging veins causes subdural hematomas, which are characterized by their crescent shape.
Subdural hematomas are not limited by sutures, can extend along the whole calvarium, falx and, tentorium (arrowheads in C and D), but are
limited by dural reflection, so they cannot pass midline.
434 Section III  Problem Solving: Disease Categories

A 30 min B 120 min

C D
Figure 12-6 Isodensity and rebleeding in subdural hematomas. A: Hyperacute subdural blood collection, imaged before clot formation,
appears isodense to the brain (arrowheads) and therefore may be overlooked, although careful attention should be posed to indirect signs such
as mass effect on the ventricles and inward displacement of the cortical gyri. B: Follow-up scan obtained 90 minutes later clearly shows shift to
hyperdensity of the subdural hematoma (arrowheads). C: Large isodense subdural hematoma (red dotted line) along its inner margins is clearly
revealed by inward displacement of the gray–white matter junction (arrowheads). D: Bilateral isodense subdural collections displace symmetrically
the gray–white matter junction inward (arrowheads).

is at high risk for rapid enlargement. Hyperacute SDH, cortical sulci and compressed ventricles (Figure 12-6).
before blood clotting, and subacute SDH can be nearly A mixed density pattern or a hemorrhagic sedimenta-
isodense with the adjacent cerebral cortex and difficult tion level may also indicate rebleeding into a preexist-
to differentiate from normal brain tissue. Acute SDH ing chronic SDH (Figure 12-6). MRI is superior to CT in
also can appear isodense to gray matter if the hemoglo- identifying the relative age of the various blood break-
bin concentration is less than 10 to 11 g/dl. Asymmetry down products of a layered, multicompartmental SDH.
of the subarachnoid spaces and inner displacement of
the cortex may reveal the presence of the isodense blood Subarachnoid and Intraventricular Hemorrhage
collection (Figure 12-6). Bilateral isodense SDHs should Traumatic subarachnoid hemorrhage (SAH) is com-
not be difficult to detect if attention is given to identify- mon. The most common cause of SAH is head trauma.
ing the displacement of gray matter with effacement of It can be caused by direct injury to the pial vessels,
 Chapter 12 Brain Trauma 435

SECTION III
E F

G
Figure 12-6, cont’d E–G: Different examples of rebleeding phenomena occurring in chronic subdural hematomas as revealed by layers and
fluid–fluid levels of different densities, suggesting coexistence of blood products of different ages.
436 Section III  Problem Solving: Disease Categories

A B

C D
Figure 12-7 Subarachnoid and intraventricular hemorrhage. Traumatic subarachnoid hemorrhage is usually more focal than what is seen in
aneurysm ruptures. Traumatic subarachnoid hemorrhage is seen in a parietal location (A, arrow) adjacent to a subdural hematoma and depressed
fracture, and in a frontal location (B, arrow), overlying the site of a contusion, with scalp hematoma. Intraventricular hemorrhage can fill the
ventricles, clot, and float attached to ventricular walls (arrowheads in C) or layer in a dependent position, usually in the ventricular trigones
(arrowheads in D).

­ emorrhagic cortical contusion, or extension of intra-

h a ­ruptured aneurysm. Traumatic SAH usually resolves
ventricular hemorrhage (IVH) into the subarachnoid over the following days.
space. Traumatic SAH is an adverse, independent, prog- As many as 25% of patients with severe head injury
nostic factor in worsening outcomes. On a nonenhanced have IVH. Traumatic IVH occurs as a result of the tear-
CT scan, acute SAH appears as linear high-density fluid ing of subependymal veins, rupture of an intracerebral
collections within the superficial sulci and CSF cisterns. hemorrhage into the adjacent ventricle, or reflux of SAH
Compared to SAH related to an aneurysm, traumatic into the ventricular system. On CT, look for a horizon-
SAH is often focal, overlying the site of cortical bruising, tally layered blood–CSF level in the dependent portions
or subjacent to an SDH (Figure 12-7). Diffuse spread of the lateral ventricles (occipital horns, if the patient is
throughout all the subarachnoid spaces is less common. supine) (Figure 12-7).
Nevertheless, if the history of trauma is unclear and The detection of acute blood into the CSF (ventricles
SAH is present, angiography should be used to identify and subarachnoid spaces) with MRI is more ­complicated.
 Chapter 12 Brain Trauma 437

SECTION III
A B

C D
Figure 12-8 Magnetic resonance imaging for detection of subarachnoid hemorrhage. Acute subarachnoid hemorrhage, seen as cerebrospinal
fluid (CSF) hyperdensity along the frontal sulci on computed tomography (A) is clearly revealed as high signal on FLAIR T2-weighted image
(arrows in B). The extreme sensitivity of FLAIR imaging for detecting subtle changes in protein concentration of CSF is counterbalanced by its poor
specificity. Infectious and neoplastic meningeal disease, as well as hyperoxygenation (frequent in patients ventilated with high concentrations of
O2 under general anesthesia) may cause similar CSF hyperintensity. Commonly observed hyperintense CSF pulsatility artifacts further decrease
FLAIR specificity in the basal and prepontine cisterns and in the ventricles (arrowheads in C and D).

The higher oxygen tension (pO2) in the CSF slows the protein ­concentration in the CSF, such as meningeal
transformation of oxyhemoglobin to paramagnetic infection or tumor, and when CSF has high oxygen con-
breakdown products such as deoxyhemoglobin and centrations (as in patients ventilated with oxygen). The
methemoglobin. Traditional T1-W or T2-W SE or fast presence of ­high-signal CSF pulsatility artifacts on FLAIR
SE sequences have not been able to detect SAH reli- further limits its specificity in identifying hemorrhage in
ably. Fast FLAIR sequences show traumatic SAH on MR the prepontine cistern, in the frontal horns of the lateral
with a sensitivity that is as good as, or even better than, ventricles, in the III and IV ventricles (Figure 12-8).
CT. SAH produces dramatic hyperintensity in the nor-
mally hypointense CSF on FLAIR due to the sensitiv- Cortical Contusions, Cerebral Hematomas, Diffuse
ity of this pulse sequence to the high protein content Axonal Injuries, Brainstem Injuries
of the blood (Figure 12-8). Nevertheless, FLAIR speci- Cerebral primary injuries occur due to impact of the
ficity fro SAH is particularly low. High CSF signal can cerebral parenchyma against the inner calvarium and
be observed that are due to other causes of increased to shear–strain forces caused by rotational acceleration
438 Section III  Problem Solving: Disease Categories

A B

C D
Figure 12-9 Different examples of cerebral contusions are seen as superficial cortical and subcortical small punctuate but sometimes larger and
confluent edematous and hemorrhagic injuries. Predilections sites are the frontal and temporal lobes, especially in areas in contact with uneven
bone surfaces, such as the ethmoid cribiform plate (arrowheads in B) and the petrous ridges.

of the head. Brain injuries consist of cortical contusions surfaces of the adjacent cribrous ethmoid plate and the
and intracerebral hematomas, diffuse axonal injury petrous ridges. Contusions occur much less frequently
(DAI), and brainstem injury. They can present with dif- in the cerebellar hemispheres, which are protected by
ferent levels of clinical severity. the smooth inner surface of the thick occipital bone.
Cortical Contusion and Intracerebral Hemato- On CT, acute brain contusions are recognized as patchy,
mas. Cerebral contusions are small, punctuate, often ill-defined cortical and subcortical low-density lesions
multiple, superficial parenchymal injuries with hemor- (edema, nonhemorrhagic contusion) containing small,
rhage and variable amounts of surrounding vasogenic hyperdense, punctate foci of petechial hemorrhage
edema, resulting from coup or contrecoup mecha- (hemorrhagic contusion), more often in the frontal and
nisms. Hemorrhagic cerebral contusions are most often temporal lobes (Figure 12-9).
encountered supratentorially. Sites of predilection Associated SAH is a common finding. In accelera-
include the anterior and inferior frontal lobes and the tion or deceleration brain injuries, a specific lesion pat-
anterior and inferior temporal lobes, due to the rough tern is often encountered, the so-called coup–contrecoup
 Chapter 12 Brain Trauma 439

SECTION III
A B
Figure 12-10 Two examples of coup–contrecoup injury revealing hemorrhagic brain contusions in opposite location across an ideal vector of
acceleration–deceleration impact type of injury mechanism. A: Left occipital injury is opposed to a right temporal pole contusion (arrowheads). B:
Right parietal lesion connects along an ideal line with the left frontal contusion. The primary site of impact is usually revealed by the soft tissue
scalp hematoma.

injury. The intraparenchymal coup injury occurs at the Depending on rotation or deceleration of adjacent
site of primary impact, which is identified by the associ- brain tissues of different density and rigidity, DAI may
ated scalp injuries or skull fractures, whereas the contre- occur in white matter or subcortical gray matter. Most
coup injury arises on the opposite side (Figure 12-10). injuries occur in gray matter–white matter junction
­Hemorrhagic cerebral contusions are more common areas of the frontal and temporal lobes or in the inter-
and tend be larger on the contrecoup side, although nal capsules. The corpus callosum or brainstem seldom
both coup and contrecoup injuries can be hemorrhagic. sustain injury without associated lesions in the lobar
A severe impact on the stationary head (e.g., a blow with white matter. Callosal injuries occur more commonly
a blunt object) results in skull fractures but generally in the posterior body and the splenium of the corpus
does not cause contrecoup contusions. This is because, callosum. In brainstem injuries, the posterior lateral
in these cases, the head does not accelerate or decelerate, quadrant of the midbrain and upper brainstem are most
and there is no brain lag. commonly involved. Shearing injuries in the cerebellum
The term cerebral hematoma refers to a well-circum- are infrequent. Despite the clinical severity, only 10% of
scribed larger parenchymal hemorrhage. Cerebral patients with DAI demonstrate significant abnormali-
hematomas tend to be found in the deeper parts of the ties on CT scan. CT may identify punctate hemorrhages
brain. Delayed development of a posttraumatic intra- in the acute setting or may reveal multiple, small, focal
cerebral hemorrhage is not uncommon and should low-density lesions in the white matter (Figure 12-12).
be suspected when the patient’s neurologic condi- However, CT underestimates DAI lesions because non-
tion is worsening. In the acute phase, hematomas hemorrhagic lesions are difficult to identify. Therefore,
may show little or no surrounding edema. However, when a patient’s neurologic or psychiatric status is worse
as the hematoma matures and clot retraction occurs, than predicted from the CT findings, MRI must be per-
the hematoma becomes surrounded by a hypodense formed (Figure 12-13). MRI is far more sensitive for
rim of edema. Hemorrhagic sedimentation levels detecting DAI lesions. FLAIR sequences are useful for
may develop (Figure 12-11). Cerebral hematomas can the detection of nonhemorrhagic lesions. Gradient echo
spontaneously decompress into the ventricles, thereby T2*-weighted images are used to detect the susceptibil-
causing IVH. ity effects of paramagnetic blood degradation products.
Diffuse Axonal Injury. The brain can suffer severe Evidence indicates that DWI is valuable in closed head
damage by shearing injuries caused by acceleration, injury because it identifies additional shearing injuries
deceleration, or rotational forces. DAI represents approx- that are not visibile on T2/FLAIR or T2* sequences.
imately 48% of all primary lesions in head trauma and Decreased apparent diffusion coefficient values can be
is one of the most common causes of poor clinical found in DAI and indicate restricted diffusion.
outcome. Clinically, DAI is characterized, in the acute Brainstem Injury. Acute posttraumatic primary brain-
phase, by impairment or complete loss of consciousness stem injury usually involves the dorsolateral aspect of
from the moment of impact. the upper midbrain, as a result of a contusion, as the
440 Section III  Problem Solving: Disease Categories

A B

C D
Figure 12-11 Four different cases of traumatic cerebral hematomas. These hematomas are generally located deep in the brain and might not be
present on the admission study but develop in the early subacute phase. The amount of surrounding vasogenic edema and mass effect is variable,
and commonly blood–fluid levels are present.
 Chapter 12 Brain Trauma 441

SECTION III
A B

C D
Figure 12-12 Diffuse axonal injuries (DAIs) on computed tomography (CT). A–D: Different cases showing the most common shearing inju-
ries locations, such as the midbrain, basal regions of the brain (here also called intermediate injuries), deep white matter, corpus callosum, and
subcortical white matter at gray–white matter junction. CT performs better at identifying hemorrhagic rather than nonhemorrhagic DAI and usu-
ally identifies them better in the early subacute stage rather than on admission scan.
442 Section III  Problem Solving: Disease Categories

E F

G H
Figure 12-12, cont’d E–H: Different images from the same severe craniocerebral trauma showing multiple complex skull fractures, multiple
punctuate hemorrhagic DAI in the deep and subcortical white matter, predominantly of the left hemisphere, and extensive, but more subtle, non-
hemorrhagic shearing injuries of the corpus callosum (arrowheads in H). The corpus callosum appears irregularly swollen and hypodense, with
bumpy contours, on the midline sagittal reformatted image (H).

­ rainstem hits the edge of the tentorium. Although this

b hypertension. It starts immediately after injury and is
lesion can be highly significant with regard to clinical sta- caused by traumatic loss of vascular autoregulation with
tus and prognosis, admission CT will show a very low per- massive vasodilation. In the initial stage the brain swell-
centage of these lesions. In doubtful cases or in patients ing is caused by diffuse increase of the cerebral blood
with unexplained clinical status, MRI might be necessary. volume, called hyperemia.
What Are the Signs of Secondary Brain ­Swelling?
Secondary Lesions Hyperemia is revealed on CT by diffuse CSF space
The clinical outcome sometimes depends on the sec- effacement, preserved gray–white matter junction vis-
ondary effects of cranial trauma: brain swelling, brain ibility, and grossly normal brain density (Figure 12-14).
herniations, vascular complications, CSF fistulae, and Hyperemia can progress to frank brain edema, usually
pneumocephalus. after 24 to 48 hours, revealed as loss of gray–white mat-
ter junction visibility and diffuse brain parenchyma
Brain Swelling hypoattenuation (Figure 12-14). The large arterial
Brain swelling with intracranial hypertension is a life- ­vessels and the venous dural sinuses might appear rela-
threatening, secondary, traumatic brain lesion. Clini- tively hyperdense compared to the brain parenchyma
cally, an increase in ICP is indicated by bradycardia and in this stage. If the ICP is not relieved, the brain will
 Chapter 12 Brain Trauma 443

SECTION III
A B C

E D F
Figure 12-13 Diffuse axonal injuries (DAIs) on magnetic resonance imaging (MRI). MRI, with its multiparametric capabilities and inherent
great sensitivity for brain signal abnormalities, is superior to computed tomography (CT) for the diagnosis and full estimation of shearing inju-
ries. Whenever the clinical picture is not completely explained by CT findings, a subtle but eloquent shearing injury should be suspected and MRI
should be performed. A, B: Patient who suffered severe acceleration–deceleration head impact and presented with otherwise unexplained right
hemiparesis. CT cut through the midbrain (A) is nonconclusive, whereas gradient-recalled echo (GRE) T2* MRI reveals a small hemorrhagic DAI
in the left cerebral peduncle (arrow in B). C–F: Another severe craniocerebral trauma patient in a coma but with no obvious hemorrhagic lesions
on CT examination (C), whose MRI shows diffuse shearing injuries of the splenium of the corpus callosum, hemorrhagic on GRE T2* image (D),
high T2 signal on FLAIR (E), and restricted diffusion on diffusion-weighted imaging b1000 (F).

g­ radually herniate through the tentorial incisura and What Are the Different Types of Brain Hernia-
the foramen magnum. tions?
1. Subfalcine herniation: Brain hemispheres can shift
Brain Herniations from side to side under the falx, with the risk of com-
Severe brain swelling and intraaxial and extraaxial hem- pression of the anterior cerebral artery (ACA) against
orrhage cause mass effect and may lead to displacement the rigid falx, possibly resulting in ACA infarcts, and
of brain tissue. The intracranial dural reflections, the falx distortion of the ventricular foramina of Monro, pos-
and the tentorium, are the boundaries of the intracra- sibly resulting in ventricular entrapment and hydro-
nial compartments and limit the amount of compensa- cephalus.
tory shift and displacement, which develop in response 2. Transtentorial descending herniation (uncal herniation):
to general or localized increased ICP. When the pressure Brain hemispheres can shift downward so that the
in one of the dural compartments increases beyond the mesial temporal lobe “slips” medially and inferiorly
physiologic compensatory mechanisms, a pressure gra- along the free margin of the tentorium. The herni-
dient ensues. This leads to brain herniation, which is a ated temporal lobe can compress the ipsilateral
displacement of brain, CSF, and blood vessels, from one oculomotor nerve and cerebral peduncle, causing
cranial compartment to another, along the free margins ipsilateral mydriasis and contralateral hemipare-
of the dural reflections, following the pressure gradient sis, or can push the contralateral cerebral peduncle
direction (Figure 12-15). against the adjacent tentorium, causing ipsilateral
444 Section III  Problem Solving: Disease Categories

A B

C D
Figure 12-14 Posttraumatic brain swelling: hyperemia and cerebral edema. A, B: Diffuse brain swelling revealed by effacement of the cerebro-
spinal fluid (CSF) spaces in the sulci along the vault (B) and of the cisterns at the base of the brain (A). Disappearance of the perimesencephalic
cistern, the so-called smile, represented here by the red dotted line crescent in A, is a very important sign of brain swelling and impending descend-
ing transtentorial herniation. Note that the natural density difference at the gray–white matter junction is preserved, so this is defined as swelling
in hyperemic state rather than brain edema. C, D: Diffuse and severe brain swelling (note effacement of CSF spaces at base and along vault) is
accompanied by homogeneous parenchymal hypodensity (blood-containing structures, such as dural sinuses and large vessels, and the tentorium
appear hyperdense compared to brain) and gray–white matter junction visibility loss. This is defined as brain swelling and diffuse cerebral edema,
a prognostically much worse condition than hyperemia.

mydriasis and ipsilateral hemiparesis, the so-called through the tentorial hiatus. As a result, the brain-
Kernohan notch syndrome or false-localizing sign. The stem is compressed and pushed downward and
posterior cerebral and ­superior cerebellar arteries can the arterial and venous pontine perforators can be
be compressed along their course lateral to the mid- stretched, possibly resulting in devastating pontine
brain, possibly resulting in infarcts in their respective hemorrhage, also known as Duret hemorrhage.
territories. 4. Transtentorial ascending herniation: Mass effect in the
3. Central herniation: In response to generalized and posterior fossa can push the superior vermis and
severe increased pressure in the supratentorial com- ­cerebellar hemispheres in the supratentorial com-
partment, the diencephalon can shift downward partment through the tentorial hiatus.
 Chapter 12 Brain Trauma 445

SECTION III
A B

C D
Figure 12-15 Brain herniations. A: Expected effects of a pressure increase in the supratentorial compartment, creating a pressure gradient
directed downward (red arrow). The brain shifts contralaterally below the falx, featuring a subfalcine herniation (yellow arrow), and caudally
across the free margin of the tentorium, featuring a transtentorial descending or uncal herniation (green arrow). B: Increased mass effect in the
posterior fossa causes the cerebellum to herniate upward through the tentorial hiatus (blue arrow) and downward through the foramen magnum
(white arrow), featuring ascending transtentorial and tonsillar herniation, respectively. C: Coronal plane display of a large subdural hematoma
compressing the right cerebral hemisphere, resulting in subfalcine herniation (arrowhead) and transtentorial herniation (arrow) that impinges on
the brainstem.

5. Tonsillar herniation: Mass effect in the posterior fossa no additional brain compression occurs against the
can push the inferior vermis and cerebellar tonsils in bony margins. Some neurosurgeons also perform
the spinal canal through the foramen magnum, pos- duraplasty, a procedure that widens the dura at the
sibly compressing the lower medulla, the vertebral level of the craniectomy, with apposition of an extra
arteries, and the posterior inferior cerebellar arteries. sheet of artificial dura.
6. Herniation through the craniectomy: To prevent brain Displacement of brain tissue across intracranial com-
herniation in the acute trauma setting, a craniectomy, partments causes compression on vital brain tissue and
often bilateral, is commonly performed to relieve stretching and compression of cranial nerves and ves-
intracranial hypertension. The swollen brain then sels, possibly resulting in profound neurologic deficits,
herniates through the craniectomy defect without ischemic infarcts, and perhaps even death. Early detec-
compressing other intracranial nervous or ­vascular tion of brain herniation is of vital importance in clinical
structures. The craniectomy should be wide so that patient management. CT is able to identify all types of
446 Section III  Problem Solving: Disease Categories

E F

G
Figure 12-15, cont’d D, E: Axial plane appearance of a right subdural hematoma causing subfalcine (D) and uncal (E) herniation. The
left lateral ventricle is entrapped and dilated. The arrow in E points to a medially displaced and dilated right temporal horn. F: Sagittal magnetic
resonance image showing mass effect in the posterior fossa with upward and downward herniation (arrowheads). G: Axial plane computed tomog-
raphy of a tonsillar herniation revealed by effacement of cerebrospinal fluid spaces around the inferior brainstem at the level of the foramen
magnum (arrowheads).

brain herniations based on direct and indirect signs of the contralateral side of the herniation. Vasospasm can
displacement. cause cerebral infarction in head injury patients, usually
induced by SAH. Direct vessel injury can occur, possibly
Vascular Complications resulting in arterial dissection, laceration, formation of
Posttraumatic ischemia and infarction are common pseudoaneurysms, arteriovenous fistula, thrombosis, or
complications in severe head injury, especially among distal embolization. Diagnosis of arterial lesions usually
patients with associated SDH, brain swelling/edema, requires CTA, digital subtraction angiography, or MRI/
and traumatic SAH. The most common cause of post- MR angiography. Related ischemic lesions are rarely evi-
traumatic infarction is extrinsic compression of a blood dent on the admission CT study but become evident on
vessel due to mechanical shift of the brain and herniation follow-up imaging studies (Figure 12-16). More rarely,
across the falx and/or tentorium (e.g., caused by EDH or cerebral fat microembolisms may occur in patients with
SDH). The infarcts can occur on the same side or on long bones fractures.
 Chapter 12 Brain Trauma 447

SECTION III
A B

C D
Figure 12-16 Posttraumatic ischemic vascular complications. A, B: Patient with head injury presented with right subdural hematoma and
descending transtentorial brain herniation. After hematoma evacuation and brain decompression was performed, follow-up computed tomogra-
phy (CT) reveals a left posterior cerebral artery (PCA) ischemic infarct involving the mesial temporooccipital lobe (arrowheads in A) and thalamus
(arrowhead in B) due to herniation-related PCA compression. C: Patient with posttraumatic subfalcine herniation underwent decompressive
craniectomy. Follow-up CT scan reveals bilateral anterior cerebral artery (ACA) ischemic infarcts (arrowheads) due to herniation-related compres-
sion of the ACAs against the falx. D: Follow-up CT images of patient who presented with severe traumatic subarachnoid hemorrhage showing
multiple and bilateral large ischemic infarcts involving arterial and watershed territories. This distribution suggests vasospasm as the responsible
injury mechanism.
448 Section III  Problem Solving: Disease Categories

On the venous side, dural venous sinus laceration is of an acute fracture. The extent of a linear or a com-
almost always associated with depressed skull fracture plex fracture can be better appreciated on panoramic
or penetrating wounds. 3D surface-shaded reformatted images, although this
technique might underestimate or overlook thin frac-
CSF Fistulae and Pneumocephalus ture lines. Particular attention is needed for fractures
CSF fistulae and pneumocephalus can occur as second- in the temporoparietal area, where the large-caliber
ary events if there is a skull fracture with an associated middle meningeal artery and its branches run along
dural laceration. Posttraumatic CSF fistulae occur in up the inner calvarium, because of frequent association
to 9% of patients with head injury. Most of these fistu- with EDH. In case of depressed fractures, inward dis-
lae close spontaneously, whereas a persistent CSF leak placement of the calvarium has to be measured and
carries significant risk for the development of meningi- reported because of the possible coexistence of adja-
tis. CSF fistulae are rarely addressed by acute imaging. cent brain injuries. The craniocervical junction should
Pneumocephalus is detected in the presence of a pene- be included in the CT evaluation and examined for
trating injury, a mastoid fracture extended to the tegmen fractures or dislocations. Skull base fractures must be
tympani, or a fracture of the inner wall of the frontal actively searched for because of possible involvement
sinuses and implies an increased risk of intracranial of the bony carotid canal, cranial nerve foramina, teg-
infection. Large pneumocephalus, as with any extraaxial men tympani, middle ear ossicles, and otic capsules.
collection, has mass effect and an irritating effect on the Fracture of the posterior wall of the frontal sinuses
brain but usually undergoes spontaneous resorption. must be ruled out in frontal impacts because of the
Noncontrast CT, visualized with bone window settings, infectious risks carried by direct communication
optimally detects even very small pneumocephalus. between the sinonasal air spaces and the intracranial
compartment. Presence of air bubbles in the intra-
Which Lesions Require Immediate Surgical cranial compartment suggests a penetrating injury or
Intervention? a fracture of the tegmen tympani, ethmoid plate, or
One of the most critical questions the radiologist needs frontal sinuses, whereas air around the temporoman-
to answer in the most timely manner is “Does this dibular joints is a strong indicator of a mastoid frac-
patient require an emergency surgical intervention?” ture (Figure 12-17).
As a general rule, because the intracranial com-
partment is a rigid closed space capable of tolerating “The Extraaxial Compartment”
only limited increase in internal pressure, all condi- CT images are viewed with standard brain parenchyma
tions characterized by significant focal mass effect or and subdural (W 150–300 HU, L 50–100 HU) window
potential for rapid evolving mass effect are candidates settings in order to visualize the thinner layers of EDH
for surgical decompression. Such conditions are repre- or SDH against the inner margins of the calvarium. Be
sented by large cerebral hematomas and large SDHs, aware that thin extraaxial hematomas along the inferior
with significant mass effect and brain herniation, and portion of the occipital squama, along the petrous ridge
almost any EDH, even of small size, due to possible and along the floor of the anterior cranial fossa, hence
rapid growth. Significant brain swelling is amenable to the ones that are parallel to the axial plane of the CT
decompressive craniectomy in order to prevent brain cuts, are easier to miss.
herniation and ischemic complications. A raise of ICP Particular attention must be directed to the mass
in the infratentorial compartment may represent a sur- effect caused by the extraaxial blood collection. Mass
gical emergency due to the limited compensatory spaces effect can be visible locally on the adjacent CSF spaces,
in the posterior fossa and the dangerous compression sulci, and brain parenchyma, or remotely on the ven-
of the brainstem’s vital structures. Depressed skull frac- tricular system, the midline brain structures, the basal
tures usually need surgical reduction to relieve brain cisterns, and the brainstem. EDHs, with their typical
compression and prevent further neuronal ­damage. biconvex shape, especially those in the temporoparietal
Ventricular shunting is performed in case of ventricu- region, must be considered with particular attention
lar hemorrhage, massive SAH, or hydrocephalus due to and alarm because they are usually caused by an arterial
ventricular incarceration. Finally, aggressive intensive bleed and can grow in size very rapidly, with possible
care management of severe head trauma often requires devastating effects. The usually associated skull fracture
the placement of a subdural or intraventricular catheter should be visualized and reported.
for invasive ICP monitoring. SDHs on the other side, with their crescentic shape,
SAH, cerebral contusions, and DAI, although possibly are usually caused by a venous bleed and hold a lesser
clinically relevant, are not lesions amenable to surgery. growth potential. However, due to their large surface of
spread, they can occupy a large volume and cause sig-
What to Look for on the Admission CT Scan nificant mass effect and brain displacement, even when
“The Container” their thickness might seem not considerable.
Review of CT images with soft tissues and bone win- Although acute extraaxial blood collections com-
dow settings allows identification of large scalp hema- monly appear hyperdense and grossly homogeneous
tomas and skull fractures. In cases of linear fractures, at the time of admission imaging, inhomogeneity and
differential must be made with sutures: sutures are nonlayered patchy isodense components within might
bilateral and symmetrical and show sclerotic mar- represent very recent and nonclotted bleed or active and/
gins, whereas no sclerosis is seen along the borders or repetitive hemorrhage, with rapid growth potential.
 Chapter 12 Brain Trauma 449

SECTION III
A B

C D
Figure 12-17 Head fractures of particular interest. A: Obvious right mastoid fracture (arrow) coursing through the middle ear. Integrity of the
ossicular chain and carotid canal and the likely cerebrospinal fluid (CSF) fistula are of special concern in these fractures. Opacification of the
contralateral mastoid and middle ear should raise the suspicion of a more subtle fracture of the left mastoid as well. B: Small linear fracture of the
posterior wall of the frontal sinus (arrow) associated with pneumocephalus (arrowhead) is at risk for intracranial infection and CSF fistula. C, D:
Air in the temporomandibular joint (arrowhead in C) is an indirect sign of a temporal bone/mastoid fracture, as confirmed in this case by fluid in
the left mastoid and direct visualization of a thin fracture line (arrow in D).

Common pitfalls are represented by invisible thin nn In the presence of IVH, early signs of developing
extraaxial collections, due to improper window-set- hydrocephalus, such as mild dilatation of the tem-
tings (Figure 12-18), and by isodense EDHs and SDHs. poral horns or convex margins of the third ventricle,
Hyperacute bleed before clot retraction and low hemo- with initial sulcal effacement, have to be ruled out.
globin concentration (<10 g/dl) in anemic patients may nn Signs of ICP have to be recognized.
cause the extraaxial hematoma to appear isodense to Generalized increase of ICP, caused by hyperemia or
the brain parenchyma (Figure 12-18). Asymmetry of brain edema, is revealed by diffuse and bilateral sulcal
the CSF spaces, sulcal effacement, and inward displace- effacement, reduced ventricular size due to compres-
ment of the gray–white matter junction depict the pres- sion, and basal cistern effacement. In young patients
ence and the location of the isodense extraaxial blood with normally small ventricles and CSF spaces, it may
collection. be difficult to judge the width of the subarachnoid
Finally, the density of the CSF spaces in the sulci must spaces along the convexities; therefore, it is advisable to
be examined to rule out SAH. evaluate the most cranial axial cuts, where CSF spaces in
the parasagittal regions should always be visible in nor-
“The Content” mal conditions (Figure 12-19). Another area to focus
CT images are visualized with standard brain paren- attention is certainly the basal cisterns, particularly the
chyma window settings. At first glance, note the ambiens cistern, around the midbrain, called the brain
­following: smile, whose effacement indicates bilateral descending
nn Obvious intraaxial hemorrhages need to be grossly transtentorial herniation and severe intracranial hyper-
measured in size, and the presence of vasogenic tension (Figure 12-19). If signs of generalized increased
edema and mass effect must be evaluated, along with ICP are observed, the next judgment required is the dif-
the presence of IVH. ferential diagnosis between hyperemia (a more benign
450 Section III  Problem Solving: Disease Categories

A B

C D
Figure 12-18 Common pitfalls in extraaxial collections. A, B: Improper window setting might underestimate or overlook small extraaxial hem-
orrhagic collections, such as these two small epidural hematomas (thin and thick arrows). C, D: Hyperacute bleeds, before clot retraction occurs,
display isodensity with the gray matter, as in this subdural hematoma (SDH) (arrowheads in C). At follow-up few hours later, the SDH is much
more obvious because of enlargement and increase in density (D).
 Chapter 12 Brain Trauma 451

SECTION III
A B C

D E F
Figure 12-19 Cerebrospinal fluid (CSF) space effacement as a sign of intracranial hypertension. In normal healthy brains, CSF space width is
highly variable. A–C: In a normal young individual, although sulci can be very tight along the convexities and in the sylvian fissures, they should
always be visible around the midbrain (ambiens cistern, arrowheads in A) and at the level of the most upper cuts along the vault (arrow in C). D–F:
Loss of visibility of the basal cisterns (arrowheads in D) and of the CSF spaces at the upper cuts along the vault (arrow in F) should raise concern
for intracranial hypertension caused by enlarged ventricles or brain swelling.

and initial condition), and brain edema (a more severe because of the risk of vascular compression of the ante-
and advanced pathologic condition). In hyperemia, rior cerebral arteries against the falx, search for early
gray–white matter junction visibility is preserved, and CT signs of ischemia in their respective vascular ter-
the brain has a normal density, whereas in brain edema, ritories, in the superior frontal gyri, along the parasag-
the brain is diffusely hypodense and gray–white mat- ittal areas. Uncal herniation is recognized by mesial
ter junction visibility is lost. If the scan was acquired in displacement of the uncus and mesial temporal lobe,
helical rather than sequential mode, be aware that the with asymmetry of the interpeduncular cistern, uni-
gray–white matter junction might be poorly visible due lateral ambiens cistern effacement, and contralateral
to “dragging” artifacts (Figure 12-20). midbrain displacement. When an uncal herniation is
Localized supratentorial increase of ICP, caused by diagnosed, due to the risk of posterior cerebral artery
intraaxial or extraaxial hemorrhage, can result in asym- and superior cerebellar artery compression between
metric sulcal effacement, ventricular compression, and the mesial temporal lobe and the midbrain, rule out
subfalcine and uncal herniation. Obvious subfalcine early signs of ischemia in the thalamus and in the tem-
brain herniation is readily appreciated by observing porooccipital regions.
the asymmetry of the lateral ventricles and the posi- Increased ICP in the posterior fossa, caused by intraax-
tion of the septum pellucidum and third ventricle in ial or extraaxial hemorrhage, is indicated by effacement
relation the midline. In case of subfalcine brain shift, of the subarachnoid spaces around the cerebellum and
452 Section III  Problem Solving: Disease Categories

A B C

D E F
Figure 12-20 Dragging artifact of helical computed tomography (CT) acquisition. Ideally the brain CT should be acquired in sequential rather
than helical mode due to the possible dragging artifact that may give the false appearance of gray–white matter junction effacement, possibly
leading to a false diagnosis of brain edema. A–C: Images of the brain acquired in helical mode having an appearance of brain hypodensity and
abnormal homogeneous density. D–F: Images obtained immediately after repeated scan in sequential mode shows brain swelling (but with pre-
served gray–white matter contrast) and diffuse subarachnoid hemorrhage.
 Chapter 12 Brain Trauma 453

SECTION III
A B

C D
Figure 12-21 Increased intracranial pressure in the posterior fossa. A–C: Occipital fracture (arrowhead on A), accompanied by left cerebellar
edematous and hemorrhagic contusion resulted in posterior fossa hypertension as demonstrated by fourth ventricle compression and effacement
(arrow in A), effacement of the prepontine cistern, and ascending transtentorial herniation, as revealed by upward displacement of the superior
vermis through the tentorial hiatus (arrows in C). These findings prompted an emergency decompressive craniectomy (arrowheads in D).

of the prepontine cistern, with compression or disloca- lesions must be sought in the anterior temporal poles
tion of the fourth ventricle. The inferior vermis and the and in the basal and orbital portion of the frontal
tonsils herniate downward through the foramen mag- lobes, with particular attention to the undersurface
num (tonsillar herniation), as revealed by effacement of the gyri recti because they rub against the uneven
of the CSF spaces around the inferior medulla on the surfaces of the ethmoidal plate at the moment of the
lower axial cuts or on reformatted sagittal images. The impact (Figure 12-22). When it is important to ­clarify
superior vermis herniates upward through the tentorial the mechanism of the head injury, whether it is due to
hiatus (ascending transtentorial herniation), filling the a fall or to a blow, look for evidence of coup–contre-
­superior vermian and the pulvinar cisterns. Direct or coup injury, which is present in acceleration–deceler-
indirect CT signs of increased ICP in the posterior fossa ation injuries but not in purely impact lesions.
require thorough and rapid reporting, representing a nn After the most immediate observations, the radiologist
possible indication to an emergency decompressive sub- should actively and carefully search for the less evi-
occipital craniectomy (Figure 12-21). dent DAI, which often is an underestimated lesion on
nn Cortical contusions revealed by a variable combina- the admission imaging and sometimes is responsible
tion of small hemorrhagic and edematous superficial for otherwise unexplained severe clinical ­conditions.
454 Section III  Problem Solving: Disease Categories

A B

C D
Figure 12-22 Hot spots for brain contusions. Subtle contusive injuries have to be searched for at the temporal poles and along the straight
gyri (arrows and arrowheads) because they are in contact with and rub against the uneven bony surface of the ethmoid cribrous plate during head
trauma.

Sites of focused attention to look for DAI are the sub- the orbital fat, might be indirect signs of a carotid–
cortical white matter at the centri semiovale, the sple- cavernous fistula (Figure 12-23).
nium of the corpus callosum, the internal capsules,
and the dorsolateral portions of the brainstem. Is There Any Facial and/or Orbital
nn Axial cuts through the brainstem itself deserve a spe-
Trauma?
cific and thorough analysis to rule out hemorrhagic
contusions, DAI, and, in case of descending transten- Facial fractures are often associated with brain trau-
torial herniation, usually in a later phase, so-called matic injuries in severe craniofacial traumas. For most
Duret hemorrhage (see section: Subacute Head Imag- isolated facial fractures, plain film radiographs are gen-
ing: Early Follow-Up and Management). erally considered a satisfactory screening imaging tool.
nn If diagnostic imaging is performed at admission to However, the need for multiple and high technical value
rule out blunt vascular injuries, look for arterial cali- views, the increasingly widespread use of MDCT in busy
ber irregularities, such as dissection-related stenosis, emergency rooms, and the frequent association of facial
beading, pseudoaneurysms, intimal flaps, and mural trauma with intracranial injuries are making MDCT a
hematomas. A dilated superior ophthalmic vein in more often used primary imaging method for diagnos-
the orbit, with exophthalmus and variable edema in ing facial and orbital fractures. This preference for CT
 Chapter 12 Brain Trauma 455

SECTION III
A B

C D
Figure 12-23 Carotid-cavernous fistula. Two months after head trauma, this patient presented with left proptosis, pulsatile eye pain, and an
orbital bruit at auscultation. Noncontrast computed tomography showing an asymmetrically enlarged superior ophthalmic vein on the left side
(arrow in A), confirmed by computed tomographic angiography (arrow in B and C). D: Carotid angiogram showing a carotid-cavernous fistula
with opacification of the left cavernous sinus in the arterial phase (arrowhead).
456 Section III  Problem Solving: Disease Categories

A B

C D E
Figure 12-24 Mandibular fractures. A, B: Bilateral mandibular condylar fractures (arrowheads in A and B) carrying the risk of malunion and
late degenerative OA of the temporomandibular joints. (Courtesy Dr. MV Spampinato, MUSC.) C–E: Three examples of mandibular fractures
involving the mandibular inferior alveolar nerve foramen (arrow in D and E) at risk for associated nerve injury.

over radiography is unfortunately accompanied by a nn Mandible: Attention should be directed to involve-

decreased level of confidence in interpreting face radio- ment of the articular condylar components and the
graphs among radiologists, who are also pressured by mandibular nerve canal (Figure 12-24). The radiolo-
the high risk of litigation. When MDCT is used, thin gist should be wary of the ‘‘flail’’ mandible, in which
slice (0.5–2.0 mm) volumetric acquisition should be a parasymphyseal fracture occurs in conjunction with
obtained, and the same datasets should be used to obtain bilateral posterior fractures, allowing posterior dis-
coronal and sagittal reformatted images, to be viewed placement of the genioglossus muscle attachment
with bone and soft tissue window settings, as well as 3D and potential difficulty in keeping a patent airway in
volume-rendering surface-shaded ­reconstructions. MRI, a patient who is lying supine. Complications include
ultrasound, color Doppler, and angiography are used to malunion, excessive mobility, infection, and tem-
perform further and targeted assessment of soft tissue poromandibular joint ankylosis resulting from intra-
or vascular abnormalities, such as lesions of the optic capsular fracture.
globe, optic nerve, and cavernous sinus. nn Ethmoid: Air cell walls act as an energy dissipating
Although very accurate systems of classification for crumple zone, resulting in complex fractures, often
facial and orbital fractures exist, a thorough description associated with CSF leaks if the dura mater is torn.
is beyond the aim of this chapter. Clinical routine usu- Nasolacrimal duct involvement can lead to nasolacri-
ally adopts a descriptive approach to diagnosing frac- mal sac mucocele.
tures of the facial bones, considering bone involvement, nn Midface: Although high-energy impact forces, such
fracture morphology and extent, displacement of osse- as those that occur in motor vehicle accidents,
ous fragments, and soft tissue involvement, with partic- often result in complex fracture patterns with com-
ular attention to “hot spots” or particular injuries with minution and displacement, the classic and simpli-
specific clinical relevance. fied ­classification of midface fractures by Le Fort
 Chapter 12 Brain Trauma 457

SECTION III
Figure 12-25 Le Fort midface fracture classification. Schematic representation of the classic Le Fort fracture classification system as it appears
on anterior and lateral views. Red line indicates type I fractures, green line type II, and blue line type III. See text for details. (Modified from Le Fort
classification of midface fractures.)

(Figure 12-25) is still used by surgeons and therefore to play a major role in the orbital examination of
is worthy of consideration. Le Fort I: horizontal frac- acute trauma patients.
ture line above the hard palate, separating the caudal The term orbital blowout fracture is used to describe a
maxilla from the midface and coursing through the fracture resulting from a blow to the orbit by an object
three walls of the maxillary sinuses, the nasal septum, too large to enter the orbit. Fractures of the orbital floor
and the pterygoid plates. Le Fort II: pyramidal fracture (sparing the rim) and the medial wall are typical. These
involving the nasoethmoidal region, the orbital floor, fractures can be accompanied by indirect signs, such as
and the anterior and posterior (not the medial) walls inferior and medial displacement of orbital soft tissue,
of the maxillary sinuses. Le Fort III: more cranial frac- respectively, in the maxillary sinus and in the ethmoid
ture line involving medial and lateral orbit walls, the air cells, orbital fat edema, orbital emphysema, and
zygomatic arch, and the pterygoid plates; maxillary fluid in the maxillary sinus. Diplopia may result from
sinuses are spared. muscle injury or entrapment of the extraocular muscles,
nn Frontal sinus: Fractures of frontal sinuses may lead to more often the inferior rectus, which usually represents
cosmetic deformity, CSF fistula, chronic meningitis, a surgical emergency (Figure 12-26). A tension pneumo-
and mucocele. Points for the radiologist to note are orbit may occasionally occur.
whether the fracture of the anterior wall extends to Roof of the orbit fractures are uncommon and are
the medial supraorbital rim or nasoethmoidal com- often associated with intracranial complications.
plex and whether there is persistent fluid in the sinus Intraocular injury is reported in 15% to 30% of
making damage to the nasofrontal recess more likely. patients with orbital fractures. Although CT may show
In this situation, the surgeon may consider sinus features of globe disruption, lens dislocation, and vit-
obliteration to prevent chronic sinusitis or mucocele. reous hemorrhage, these abnormalities are often bet-
Detection of a posterior wall fracture is often associ- ter demonstrated with ultrasound. When intraocular
ated with intracranial injuries and requires a careful and intraconal causes of posttraumatic visual loss have
study for extension to the anterior skull base, intra- been excluded, visual impairment is usually due to optic
cranial air, and any displaced fragments that may lead nerve injury, edema or ischemia, or perineural or retro-
the surgeon to consider sinus cranialization to prevent bulbar hematoma. Compression of the optic nerve most
CSF leak and meningitis. frequently occurs within the intracanalicular segment.
nn Orbits: In patients with acute orbital trauma, visual Any fracture of the orbital roof, lamina papyracea, and
acuity and extraocular muscle motility are the two sphenoid bone body should prompt careful analysis of
most important ophthalmologic functions to be eval- the optic canal.
uated emergently. Assessment of these capabilities Foreign bodies in the orbit may be intraocular or
may be difficult due to the severity of the head injury, extraocular. Intraorbital displaced bone fragments can
the extent of periorbital soft tissue edema, inadequate cause entrapment, nerve, and vascular injury and usu-
cooperation from alert patients, and reduced level of ally require surgical removal. Although radiopaque
consciousness in obtunded individuals. CT has come foreign bodies do not represent a diagnostic problem,
458 Section III  Problem Solving: Disease Categories

A B

C D
Figure 12-26 Orbital floor fracture and extraocular muscle entrapment. A–D: Fracture of the floor of the right orbit (arrowheads in A–C) com-
plicated by herniation in the adjacent maxillary sinus of orbital soft tissues. D: Coronal image with soft tissue window settings showing distortion
and inferior deviation of the inferior rectus (arrowhead) and mixed density of the herniated soft tissues, composed of fat and muscle (arrow). The
patient presented with diplopia and upward gaze limitation due to the muscle entrapment, which required emergent surgical correction.

the radiologist should be aware that wooden frag- Which Imaging Is Best?
ments are markedly hypodense and may mimic loc- In this phase when patients usually are monitored in
ules of air if images are viewed with narrow window an intensive care unit, the most rapid, accessible, cost-
settings. effective, satisfactory, and comparable imaging method
remains CT. MRI in these patients is reserved for those
cases whose clinical findings are not explained by the CT
SUBACUTE HEAD IMAGING: EARLY findings and is mainly aimed at detecting subtle brain-
FOLLOW-UP AND MANAGEMENT stem injuries or better defining location and extent of DAI.

What Is the Most Optimal Imaging Postsurgical Imaging

Approach to Follow-up in Different The main classes of surgical procedures performed on
Clinical Settings? acute head trauma patients are
nn drainage of intraaxial and extraaxial hematomas
After acute head trauma admission imaging, further nn decompressive craniectomies
imaging is obtained in the following settings: nn placement of intracranial catheters
nn Follow-up imaging in patients who have undergone After surgical drainage of intraaxial or extraaxial hema-
surgical procedures tomas, the radiologist should note the type of surgical
nn Routine serial follow-up imaging procedure that was performed. When comparing pre-
nn Follow-up imaging focused toward a new clinical surgical and postsurgical studies, it is important to note
issue whether the drainage has been completely or ­partially
 Chapter 12 Brain Trauma 459

SECTION III
A B C

D E F
Figure 12-27 Postsurgical follow-up. A, B: Follow-up of surgical treatment of a large epidural hematoma. B: Decompression with resolution
of midline shift and a new small epidural hematoma (arrow) at the anterior edge of the craniotomy that will require close radiologic follow-
up because of its rapid growth potential. C, D: Craniectomy performed to decompress the right hemisphere from a subdural hematoma and a
depressed skull fracture. The hematoma has been drained, but the midline shift persists and appears increased (arrow in D) partly due to paren-
chymal plasticity and especially due to a new cerebrospinal fluid subdural collection on the right side (arrowhead in D), with mass effect. E, F:
Bilateral decompressive craniectomy performed to relieve intracranial pressure in this patient with hyperemic brain swelling (E). F: Postsurgical
follow-up shows subfalcine herniation (arrows) due to the mass effect of a large heterogeneous epidural hematoma that developed at the site of
the right craniectomy (arrowhead).

successful and whether rebleeding has occurred, locally ­ emorrhagic lesion in the ventral portion of the pons
h
or remotely. The decompressive result of the drainage seen in association with uncal herniation, so-called
must be evaluated, looking at the signs of intracranial Duret hemorrhage (Figure 12-28). After craniotomy, the
hypertension and brain herniation: Are the subarach- dura is detached from the inner calvarium, and, despite
noid spaces reexpanded? Are the midline structures back the reanchoring surgical attempt, it is usually very dif-
in place? Are the cisterns around the midbrain patent? ficult to discern the epidural from the subdural location
Has the ventricular incarceration resolved? Is there evo- of fluid or hemorrhagic extraaxial collections unless the
lution of the lesions seen at admission? dura itself is visible.
Often a severe displacement of the brain tends to per- In case of brain swelling and often after hematoma
sist on the first follow-up studies after decompression drainage, a decompressive craniectomy is performed,
due to brain parenchymal plasticity (Figure 12-27). In usually in association with a duraplasty. On the post-
these cases, the place of the hematoma can be tempo- surgical study it is important to evaluate the effect of the
rarily occupied by CSF. Sometimes a decompression is craniectomy on the pressure equilibria in the intracra-
complicated by ex vacuo contralateral SDH or hygroma. nial compartment. Have the brain, ventricles, and CSF
After decompression, some hemorrhagic, edematous, spaces reexpanded? Are the cisterns around the midbrain
and ischemic lesions appear more evident. Particular patent? Are the craniectomy and the duraplasty wide
attention must be directed to the brainstem: During enough to allow the brain to protrude freely through the
descending transtentorial herniation the brainstem craniectomy? Are extraaxial fluid or hemorrhagic collec-
is pushed downward and stretching of the perforat- tions limiting the degree of decompression? Has the
ing pontine arteries might cause the typical and severe decompression caused a contralateral SDH or hygroma?
460 Section III  Problem Solving: Disease Categories

A B C

D E F
Figure 12-28 Duret hemorrhage, a specific type of brainstem hemorrhage that can be observed in patients who suffer descending transtentorial
herniation (see text for details). It usually is better visualized in the subacute phase, at follow-up imaging, when the brain herniation has been
decompressed. (A, B), (C, D), and (E, F) show three examples of patients with extraaxial hematoma and uncal herniation (A, C, E) who devel-
oped Duret brainstem hemorrhage (arrows in B, D, F), visible after surgical decompression. Arrowheads in D point to a posterior cerebral artery
ischemic infarct caused by brain herniation.

Intracranial catheters can be inserted in the ventricles Interval Evolution of Primary Lesions
or in the subdural space for drainage and ICP ­monitoring. When hemorrhagic extraaxial collections are not surgi-
An intraparenchymal catheter can be used, usually in cally drained and a conservative approach is chosen,
children, for ICP monitoring purposes. The role of radi- imaging follow-up is requested to evaluate signs of
ologist is to verify the correct positioning of the catheters, growth and increased mass effect of extraaxial hema-
their site of insertion, course, and distal tip position, and tomas. New evidence of mixed density or different
to report complications and visible effects on ventricular density layering might indicate rebleeding. It is note-
and subarachnoid spaces if a drainage is attempted. worthy that the mass effect caused by an enlarging
EDH is usually greater than the mass effect caused by
Routine Serial Follow-up Imaging an SDH, due to the rapidity and the more focal nature
nn Why? of the compression, which does not allow the brain to
To follow up the evolution of acute lesions and of adapt and conform to the mass.
delayed secondary lesions, to detect new lesions In case of traumatic SAH, rebleeding is very rare. Most
not present or not visible at the admission imaging, times at the follow-up imaging, a stable appearance
and to monitor indirectly the ICP in patients under or progressive resorption of the hyperdense blood in
sedation with no intracranial catheters. the subarachnoid space is observed.
nn When? Primary parenchymal lesions, such as cerebral hema-
After admission imaging, a follow-up CT is usually tomas, cerebral contusions, and DAI, are very likely
obtained at 24 hours. Earlier follow-up at 12 hours to change appearance and size from the admission
is recommended if the admission imaging was imaging through the follow-up studies. Rebleed-
performed less than 6 hours after the trauma or ing, increased edematous changes, hemorrhagic
in presence of risk factors, such as anticoagula- transformation of edematous lesions, confluence of
tion, hypotension at admission, or posterior fossa lesions, and fluid–blood layering can be seen (Figure
lesions (Figure 12-29). 12-30). Edema that is associated with intracerebral
nn What? hemorrhagic contusions often increases ­dramatically
 Chapter 12 Brain Trauma 461

SECTION III
CT1 @ admission

Negative Positive

Low AP @ adm. No RF CT1 >6 h after CT1 <6 h after

or coagulopathy trauma, no RF trauma, RF, PFI

CT2 @ 12 h CT2 @ 24 h CT2 @ 12 h CT2 @ 24 h

CT3 when clinically indicated

or @ 72 h

Figure 12-29 Recommended intervals of follow-up head imaging after admission imaging. AP, arterial pressure; adm, admission; RF, risk fac-
tors; PFI, posterior fossa injuries.

during the days following the acute event. It is not Ischemic infarcts represent a frequent complication in
unusual for the initial CT scan to show no, or only severe head trauma. They are usually visible at fol-
limited, edema and for follow-up examination to low-up imaging. Infarcts can occur very early after
reveal massive perilesional edema and associated the trauma but be invisible at the time of admission
mass effect. The majority of relevant CT changes imaging, or they can occur in the hours or days fol-
develop within 48 hours after injury; therefore, serial lowing the trauma. Ischemic infarctions are more fre-
imaging with early control CT scan is recommended. quently caused by arterial compression due to brain
These ­modifications are due to the normal tempo- herniations. In case of subfalcine herniation, the
ral evolution of the parenchymal lesions and to the expected infarcted areas are in the anterior cerebral
general interval changes in the intracranial compart- artery territory, whereas in case of uncal herniation
ment. For example, it is not uncommon to better see the expected infarcts involve the posterior thalamus,
DAI or to observe intracerebral hematomas enlarge the temporooccipital lobes, and the superior cerebel-
after a craniectomy that has relieved intracranial lum, along the distribution of the posterior cerebral
hypertension. and superior cerebellar arteries. Massive brain shift
and swelling can result in compression of basically
Interval Evolution of Secondary Lesions all major arteries of the circle of Willis, resulting in
In the hours and days after the trauma, relevant intracra- extremely extensive infarcts (Figure 12-32). Less fre-
nial changes, lesion evolution, and complications have quent causes of ischemia are embolic phenomena
to be expected. from arterial dissection, vasospasm (if SAH is pres-
Brain swelling initially due to hyperemia can gradually ent), and excitotoxic injuries.
progress and evolve into brain edema. This shift is Special attention must be directed to ventricular size
signaled by loss of visibility of the gray–white mat- changes. Increased brain edema tends to reduce
ter junction, diffuse parenchymal hypodensity, and the size of the ventricles; on the other hand, hydro-
progressive effacement of the CSF spaces in the basal cephalus can occur. In a swollen brain, with efface-
region and along the convexities. As previously men- ment of the CSF spaces and reduced compensatory
tioned, brain swelling is usually accompanied by reserve, even a minimal increase in ventricular vol-
brain herniations. The most frequent type of brain ume can cause a significant ICP rise and worsening
herniation, the descending transtentorial herniation, clinical conditions. Therefore it is a special responsi-
is revealed by progressive effacement of ambiens cis- bility of the neuroradiologist to detect in serial scans
tern, the so-called disappearance of the “brain smile.” the more subtle signs of developing hydrocephalus,
The generalized parenchymal hypodensity is more such as a slight increase in size of the temporal horns
striking when compared to the adjacent vascular or mild convexity of the walls of the third ventricle.
structures, which appear hyperdense, and to the supe- In addition, brain herniation can cause ventricular
rior portion of the cerebellum. The cerebellar folia are entrapment, followed by monoventricular or com-
more resistant than the cerebral hemispheres to the partmental hydrocephalus.
edematous changes, so axial CT cuts through the ten- Dural tears can cause CSF fistulas, but more often they
torial hiatus show the contrast between the normal will result in subdural hygroma, typically crescentic
cerebellar density and the hypodense temporal and in morphology, CSF-like in density, and with variable
occipital lobes, recognizable as the “dense cerebel- mass effect. Although the subdural hygroma can occur
lum” sign (Figure 12-31). anywhere in the supratentorial and infratentorial
462 Section III  Problem Solving: Disease Categories

A B

C D
Figure 12-30 Evolution of primary lesions. Dramatic changes in appearance, number, and size of primary traumatic lesions seen at admission
computed tomography are common occurrences. A, B: Small punctate hemorrhagic contusions in the frontal lobes (A) can develop into large
brain hematomas a few hours later (B). C, D: After drainage of a frontal subdural hematoma (C), large edematous and hemorrhagic contusive
lesions appear (D) in areas that showed no visible parenchymal lesions at the time of the admission scan.
 Chapter 12 Brain Trauma 463

SECTION III
A B

C D
Figure 12-31 Brain edema and the “dense cerebellum sign.” A–D: Multiplanar reformatted images of a noncontrast computed tomographic
scan of a child with severe posttraumatic cerebral edema. The cerebral hemispheres are swollen and abnormally hypodense and homogeneous,
with loss of gray–white matter contrast and sulcal effacement. The supratentorial hypodensity is striking compared to normal cerebellar density.
The cerebellum is more resistant than the cerebral hemispheres to edematous changes. Blood-containing structures such as the middle cerebral
arteries (arrows in A) and the venous sinuses (arrowhead in C) also appear relatively hyperdense to the brain.
464 Section III  Problem Solving: Disease Categories

A B C
Figure 12-32 Complications of brain herniation. Massive brain shift can result in severe compression of all major intracranial arteries, possibly
leading to extensive holohemispheric infarcts. A: Normal magnetic resonance angiogram of the circle of Willis. Red arrows point to the three major
arteries branching off the anastomotic circle. In brain herniation, the anterior cerebral artery can be compressed against the falx by the displaced
frontal lobe, the posterior cerebral artery can be compressed between the brainstem and the medial temporal lobe, and the middle cerebral artery
can be distorted and compressed along its horizontal cisternal M1 segment. Massive subfalcine and descending transtentorial brain shift causes
the ischemic infarct and in turn is further complicated by the ensuing brain edema (B, C), revealed by the parenchymal hypodensity and swelling.

compartments, they are often located in the fron- earlier, lesions with mass effect, brain swelling, ventricu-
tal region and can be bilateral (Figure 12-33). In lar morphology and size, patency of CSF spaces along
patients with wide CSF spaces, the differential diag- the convexities, in the basal cisterns, and in the posterior
nosis between bilateral subdural hygromas and brain fossa, brain herniations, and their serial changes must
volume loss is usually obtained by detection of mass be evaluated. Their final effect as a whole on the ­volume
effect and displacement of the bridging veins toward and pressure equilibrium of the intracranial compart-
the pial surface in the former and stretching of the ment can serve as a tool to grossly assess signs of intra-
veins in the latter (better seen on contrast CT or MR) cranial hypertension. Careful reporting of imaging
(Figure 12-33). findings, along with clinical data, can guide the invasive
or conservative treatment.
New Lesions
New lesions that were not present or simply not visible Follow-up Imaging Focused toward a New
at the acute admission imaging can appear on follow- Clinical Issue
up studies. New SDH or cerebral hematomas can pres- Additional follow-up imaging can be obtained in the
ent; DAI are usually much better evident hours after presence of new clinical issues, such as unexpected
the trauma either because of the increase in vasogenic increased ICP >25 mmHg, anisocoria, focal neurologic
edema or because of their hemorrhagic transformation. signs, and seizures, to detect any treatable complication
Associated with uncal herniation, a delayed focal and or evolution of primary or secondary lesions.
very severe hemorrhagic lesion in the brainstem occurs More advanced imaging, usually performed with MRI,
and is revealed by CT or to better advantage by MR. This is necessary when the clinical picture is not fully explained
lesion, called Duret hemorrhage (Figure 12-28), is differ- by CT findings. MRI is more sensitive than CT for the
ent from contusive lesions and brainstem DAI. Duret detection of thin SDHs or small cortical contusions, but
hemorrhage usually is located in a central or ventral it is mainly used in patients with unexplained comatose
location in the pons or midbrain, whereas contusions conditions to assess the presence and extent of DAI, espe-
and DAI more frequently involve the dorsolateral por- cially with nonhemorrhagic lesions, that are distributed
tions of the brainstem. Duret hemorrhage probably is in particular locations, such as the corpus ­callosum and
due to stretching and laceration of the perforating arte- brainstem. Small Duret hemorrhages of the brainstem
rial branches of the basilar artery following downward are also detected to better advantage by MRI.
displacement of the brainstem caused by descending
transtentorial herniation. CHRONIC IMAGING: TRAUMATIC
SEQUELAE AND LATE
ICP Monitoring
COMPLICATIONS
Serial subacute imaging can serve as a tool to explain
unexpected ICP increases in patients with intracranial Imaging at a long distance from the trauma may be
monitoring or to assess indirect evaluation of ICP in necessary to evaluate the sequelae of head trauma and
patients without invasive ICP monitoring. As explained to investigate the presence of lesions responsible for
 Chapter 12 Brain Trauma 465

SECTION III
A B C

D E F
Figure 12-33 Subdural hygroma. A–C: Follow-up neuroimaging of a patient with head trauma, showing progressive enlargement of bilateral,
extraaxial, subdural, frontal, and cerebrospinal fluid (CSF)-like density/signal fluid collections (arrowheads in B and C), causing progressive mass
effect on the frontal lobes. D–F: Elements of differential diagnosis between subdural hygroma (D, E) and CSF space expansion due to brain vol-
ume loss (F). Hygromas tend to compress the brain, effacing the sulci, and displace the vessels inward, toward the pial surface (arrows in D and
E), whereas in brain volume loss the CSF spaces and the sulci are widened, no mass effect is seen, and the vessels are seen stretched and coursing
across the subarachnoid space (arrowhead in F).

­ ermanent or newly developed clinical signs and symp-

p studies are required to address the particular issues, as
toms. In other cases, imaging can be obtained for other ­follows:.
reasons, and the signs of an old head trauma can repre- nn The patient has developed epilepsy.
sent incidental findings. The culprit most likely is a cortical gliotic or enceph-
Patients who have suffered head trauma can pres- alomalacic supratentorial lesion as a result of
ent with permanent focal neurologic deficits, seizures, contusive or ischemic injury. MRI is the imaging
headaches, behavioral or cognitive problems, CSF rhi- method of choice to detect subtle cortical abnor-
norrhea, anosmia, and hypoacusia. malities. FLAIR T2-WI is the sequence of choice
CT and MR can serve as complementary imaging to detect subtle signal abnormalities of the brain
diagnostic tools in the chronic setting, with scanning parenchyma adjacent to the CSF, and GRE T2*-WI
techniques targeted to the diagnostic questions. is very sensitive to foci of hemorrhage in the late
Although a general imaging assessment of the stage due to the susceptibility effect and bloom-
sequelae of head trauma is used to evaluate the correct ing artifacts created by hemosiderin deposits. The
repositioning of the craniectomy operculum, the reso- anterior and basal frontal regions, the temporal
lution of extraaxial collections, the presence of gliotic lobes, and the occipital poles deserve most of the
or encephalomalacic changes, and volume loss and attention. Hemorrhagic and nonhemorrhagic DAI
ventricular enlargement (Figure 12-34) in the presence sequelae are best assessed by FLAIR T2-WI and
of specific clinical conditions, more focused imaging GRE T2*-WI.
466 Section III  Problem Solving: Disease Categories

A B C
Figure 12-34 General late subacute head trauma imaging follow-up. A–C: Follow-up imaging of severe head trauma in a patient who under-
went bilateral decompressive craniectomies (A). Brain edema gradually subsided (B), eventually allowing the repositioning of the craniectomy
operculum (C). C: Final assessment of permanent encephalomalacic changes, brain volume loss, and compensatory ventricular enlargement.

nn The patient has clear fluid rhinorrhea and positional findings and when a history of past head trauma
headache. is not given. Typical old traumatic lesion patterns
The working diagnosis is a CSF fistula caused by arach- include cortical and subcortical amputation with
noid and dural tear in communication with a bone gliosis, often bilateral, of the frontal rectus gyrus,
defect in the region of the petrous ridges (mastoid supraorbital gyrus, and temporal poles. These
and tegmen tympani), sella, ethmoid plate, or fron- structures are likely to suffer contusion and injury
tal sinuses. Targeted CT study, with bone algorithm, from rubbing against the uneven surfaces of the
thin slice acquisition, and multiplanar reformat- anterior and middle cranial fossae. Another very
ting, is able to show small bony defect along the typical finding in the late stages after trauma is evi-
inner surface of the skull, whereas MR with high dence of bilateral and symmetrical leukoencepha-
resolution T2-WI or heavily T2-W cisternographic lopathic changes in the anterior frontal subcortical
techniques shows the dural defect and herniation and deep white matter, resembling the horns of
of CSF spaces and rules out encephaloceles (Figure a moose, called the “moose sign” (Figure 12-37).
12-35). Sometimes the fistulous site is not found Such changes are often misdiagnosed as chronic
on conventional imaging, but CSF collection can be ischemic lesions, but their distribution in the ante-
found in the mastoid cells, middle ear cavities, or rior and basal frontal lobes, across the vascular ter-
ethmoid cells, indicating the possible site to address ritories of the anterior and middle cerebral arteries
by surgical repair. A striking indirect sign of chronic and often accompanied by the lesions in the gyri
CSF hypotension caused by the fistula is repre- recti, should orient toward the correct diagnosis.
sented by generalized thickening and enhancement
of the dura, better seen on fat-suppressed enhanced PEDIATRIC HEAD TRAUMA
T1-WI, along with sagging of the brain on sagittal
images and expansion of the venous dural sinuses How to Problem Solve and
and pituitary gland (Figure 12-35). Approach the Peculiarities?
nn The patient has lost the function of smell.
Loss of smell, called anosmia, is a frequent condition The head, skull, and brain present different charac-
after severe head trauma. It is caused by lesion of teristics in children and adults, so the pathophysiol-
the thin olfactory nerve fibers that travel from the ogy of pediatric head trauma and consequently its
nasal mucosa through the cribrous ethmoid plate, imaging have a few peculiarities that are important
to the olfactory bulbs, just below the gyri recti of to know.
the anterior frontal lobes, and can be sheared by
acceleration–deceleration forces of the brain. MRI, Labor and Delivery Head Trauma
with high-resolution coronal T2-WI or cisterno-
graphic sequences, can visualize the CSF space Labor and delivery, even when uneventful, is a form of
of the olfactory grooves along the ethmoid plate physiologic trauma that can cause minor head injuries,
and show atrophy of the olfactory bulbs as a late most often with no clinical consequences. These minor
sequela (Figure 12-36). and benign traumatic injuries need to be differentiated
nn Incidental findings. from the more serious injuries related to complica-
Some lesion patterns can be recognized as traumatic tions that occurred during labor and delivery, such as
lesions, even when they are noted as incidental hypoxic–ischemic damage.
 Chapter 12 Brain Trauma 467

SECTION III
A B

C D E
Figure 12-35 Posttraumatic cerebrospinal fluid (CSF) fistula. A: In a patient with CSF rhinorrhea after head trauma, thin coronal head com-
puted tomography cuts with bone window settings shows a bony defect in the ethmoid plate (arrow) and obliteration of the adjacent sphenoid
sinus, suggesting CSF leak. B: In preoperative planning, magnetic resonance imaging with cisternographic thin partitions is required to further
characterize the fistula, here complicated by herniation of the dura, arachnoid space, and part of the right straight gyrus (arrowhead), configuring
a posttraumatic meningoencephalocele. C–E: Gadolinium-enhanced magnetic resonance imaging in another patient with CSF fistula showing
indirect signs of chronic intracranial hypotension, characterized by diffuse dural thickening and enhancement, venous dural sinus expansion,
pituitary gland enlargement, and sagging of the brain across the tentorium and foramen magnum.
468 Section III  Problem Solving: Disease Categories

B
Figure 12-36 Posttraumatic anosmia in a patient with posttrau-
matic loss of smell. Magnetic resonance imaging showing encepha-
lomalacia of the straight gyri (white arrowheads in A) and coronal
T2-weighted image demonstrating atrophy of the olfactory bulbs
revealed by cerebrospinal fluid signal and absence of normal olfactory
bulbs in the olfactory grooves (black arrowheads in B).

C
Figure 12-37 Posttraumatic bifrontal leukoencephalopathy (the
“moose sign”). Different examples of bilateral frontal subcortical
white matter gliotic changes, a typical posttraumatic contusive sequela,
resembling the horns of a moose. This can be an incidental finding,
often misdiagnosed as ischemic lesions, but prior head trauma should
be inquired for when obtaining the patient’s history.
 Chapter 12 Brain Trauma 469

SECTION III
A B C

D E
Figure 12-38 Delivery-related head trauma. A: Cephalohematoma in the typical subperiosteal location, expanding the periosteum, confined
by sutures. B, C: Depressed skull fracture, with the feature of a deformation rather than a true fracture (arrowhead on C), due to the calvarium plas-
ticity in newborns (Courtesy Dr. F. Velardi, Rome, Italy.) D, E: Typical asymptomatic incidental small subdural hematomas at the falcotentorial
junction (arrowheads in D) and in the posterior fossa (arrows in E) can be considered part of the physiologic trauma of delivery.

Head injuries seen in neonates just after delivery nn Intracranial extraaxial hemorrhages: The most common
(Figure 12-38) can be classified as follows: intracranial extraaxial hemorrhages are SDHs. Very
nn Extracranial hemorrhages: These range from the most often these SDHs are small and are seen as incidental
superficial, so-called caput succedaneum, which is findings at the junction of falx and tentorium, with
hemorrhagic thickening of the superficial scalp soft no significant mass effect. In these cases the radiologic
tissues, mobile at palpation, for which imaging is not report should state that such an SDH can be consid-
required; to subgaleal hematoma, which is located deep ered a relatively normal finding, related to the physi-
to the galea capitis, superficial to the skull, mobile ologic trauma of delivery. SAH is rare in neonates,
at palpation; and finally cephalohematoma, which is more frequently observed in preterm babies.
a subperiosteal hematoma that remodels the perios- nn Intraaxial injuries: Cortical contusions, although rare,
teum, is hard and nonmobile at palpation, stops at can be seen in association with SDHs and fractures.
the sutures, and can be seen in association with frac-
tures and intracranial injuries. Postnatal Pediatric Head Trauma
nn Fractures: These can be result from uterine contrac-
tions or compression against the pelvic ring bones Which Factors Account for the Peculiarities
during delivery. The skull fractures can be linear or of Pediatric Head Trauma?
depressed, sometimes with the appearance of a focal nn Clinical assessment of children is difficult. The his-
impression and deformation rather than a true bony tory often is unreliable, and a history of loss of con-
fracture. Overlapping displaced sutures can also be sciousness can be impossible to establish. For these
seen, and they usually spontaneously resolve. reasons, clinicians should have a low threshold for
470 Section III  Problem Solving: Disease Categories

A B

C D
Figure 12-39 Pediatric skull fracture peculiarities. A, B: “Ping-pong fracture” resulting from direct impact on the calvarium. There are no frac-
ture lines but inward focal depression of the deformable skull (arrow in A, arrowhead in B). C, D: Two different stages of growing fractures. C: Small
outpouching of arachnoid and cerebrospinal fluid (CSF) through a small fracture line (arrowhead). D: CSF pulsatility can expand the fracture line
and result in larger herniation of intracranial structures through the bony defect (arrowhead). (Courtesy Dr. A. Rossi, Genoa, Italy).

ordering neuroimaging studies in children. In par- nn The pediatric skull has plasticity and deformability,
ticular, age less than 2 years is itself a risk factor that which account for EDHs and brain contusions that
should prompt head imaging after significant head occur in the absence of skull fractures, the peculiar
trauma. Every effort should be made to minimize appearance of the so-called ping-pong fracture (Figure
radiation dose during CT imaging of the head and 12-39), a depressed fracture with the appearance of a
cervical spine while ensuring that image quality and squished table-tennis ball, and the increased risk of
coverage are sufficient to achieve an adequate diag- dural lacerations. In children younger than 3 years
nostic study. fractures can evolve into “growing fractures” (Figure
nn In children, the ratio of head to body weight is higher 12-39). These fractures show progressive enlargement
than in adults (about 10%) and neck muscles are rela- of the fracture defect, usually greater than 3 to 4 mm,
tively weak, which account for the potential for more due to meningeal interposition and CSF pulsatility,
violent head impact and higher acceleration/decelera- possibly leading to meningoceles and encephaloceles
tion forces applied to the head. of variable size.
 Chapter 12 Brain Trauma 471

SECTION III
A B C

D E
Figure 12-40 A–E: Neuroimaging of child abuse. Bilateral subdural hematomas (arrows on A and B), with different magnetic resonance signals
suggesting different ages. Blood–fluid levels in the dependent regions (arrowheads on B) suggest rebleeding phenomena, along with pericerebellar
hygromas, and hemorrhagic axonal injuries “blooming” on gradient-recalled echo T2* (C). Bilateral excitotoxic injuries in a nonvascular distribu-
tion, visible on computed tomography (D) and diffusion-weighted imaging (E), are almost pathognomonic of shaken baby injuries until proven
otherwise.

nn The brain parenchyma is soft and poorly myelinated smaller traumatic brain injuries. The presence of a lac-
so delamination injuries can occur in acceleration/ tate (Lac) peak on MR spectroscopy has proved to be
deceleration traumas. an early bad prognostic indicator in children with a
nn The CSF spaces are wide, which accounts for the normal-appearing brain on MRI acquired in the acute
incidence of SDHs due to rupture of bridging veins. or early subacute phase after head trauma.
Moreover, the presence of unfused sutures and fonta-
nelles allows intracranial hemorrhages to reach con- Nonaccidental Head Trauma:
siderable volumes before clinical signs are seen, so Child Abuse
the clinical evolution of intracranial hemorrhages in
children is often characterized by lucid intervals and In infants and young children, the possibility of nonac-
sudden deterioration. cidental injury should always be kept in mind. The radi-
nn Immature autoregulation and increased vasoreactiv- ologist plays an important role in accurately identifying
ity make hyperemia and brain swelling more frequent nonaccidental cranial trauma and is in the front line for
subacute complications of head trauma in children, suggesting the possibility of child abuse.
usually 24 to 48 hours after the primary event. Child abuse should be suspected in presence of dis-
nn The developing brain is particularly susceptible to proportion between the neuroradiologic findings (Fig-
apoptotic neuronal death following traumatic injury, ure 12-40) and the referred clinical history. Skull x-ray
which accounts for the not rarely observed rapid and films, as part of a series of plain x-ray films (skeletal
extensive encephalomalacic evolution of initially survey), retain a role in detecting nonaccidental head
472 Section III  Problem Solving: Disease Categories

injuries in children. CT is able to detect skull fractures Grossman RI, Yousem DM. Head trauma. In: Grossman RI, Yousem DM, eds.
Neuroradiology: the Requisites. 2nd ed. Philadelphia: Mosby; 2003:243-272.
and typical bilateral SDHs, often parasagittal, often Holm L, Cassidy JD, Carroll LJ, Borg J. Neurotrauma Task Force on Mild
of different ages, with signs of rebleeding. MRI with Traumatic Brain Injury of the WHO Collaborating Centre. Summary of the
FLAIR images is much more sensitive for small SDHs WHO Collaborating Centre for Neurotrauma Task Force on Mild Traumatic
Brain Injury. J Rehabil Med. 2005 May;37(3):137-141.
and is accurate in detecting rebleeding of different ages, Lee HJ, Jilani M, Frohman L, Baker S. CT of orbital trauma. Emerg Radiol. 2004
whereas DWI is extremely sensitive for detecting the Feb;10(4):168-172.
Lobato RD, Gomez PA, Alday R, et al. Sequential computerized tomography
usually associated acute parenchymal injuries, espe- changes and related final outcome in severe head injury patients. Acta
cially in shaken babies, represented by contusions, DAI, Neurochir (Wien). 1997;139(5):385-391.
and hypoxic–ischemic and excitotoxic injuries. If the Nortje J, Menon DK. Traumatic brain injury: physiology, mechanisms, and
outcome. Curr Opin Neurol. 2004 Dec;17(6):711-718:Review.
red flag of a suspected child abuse has been raised, MRI, Parizel PM, Ceulemans B, Laridon A, Ozsarlak O, Van Goethem JW, Jorens
including fast FLAIR and DWI, should be performed PG. Cortical hypoxic-ischemic brain damage in shaken-baby (shaken
as soon as possible (on the day of admission). DWI is impact) syndrome: value of diffusion-weighted MRI. Pediatr Radiol. 2003
Dec;33(12):868-871.
the most sensitive and specific method of confirming a Parizel PM, Makkat S, Jorens PG, et al. Brainstem hemorrhage in descending
shaking injury. transtentorial herniation (Duret hemorrhage). Intensive Care Med. 2002
Jan;28(1):85-88.
In chronic phases, brain volume loss due to diffuse Parizel PM, Ozsarlak Van Goethem JW, et al. Imaging findings in diffuse axonal
atrophy and SDHs of different ages can be seen. injury after closed head trauma. Eur Radiol. 1998;8(6):960-965.
Associated evidence of long bone fractures and reti- Parizel PM, Van Goethem JW, Ozsarlak O, Maes M, Phillips CD. New
developments in the neuroradiological diagnosis of craniocerebral trauma.
nal hemorrhages reinforce the diagnosis of child abuse. Eur Radiol. 2005 Mar;15(3):569-581:Review.
Poussaint TY, Moeller KK. Imaging of pediatric head trauma. Neuroimaging Clin
N Am.. 2002 May;12(2):271-294:ix. Review.
Suggested Readings Sklar EM. What more can MR imaging teach us about brain injury? AJNR Am J
Neuroradiol. 2000 May;21(5):808-809.
Brandstack N, Kurki T, Tenovuo O, Isoniemi H. MR imaging of head trauma: Sliker CW, Mirvis SE. Imaging of blunt cerebrovascular injuries. Eur J Radiol.
visibility of contusions and other intraparenchymal injuries in early and 2007 Oct;64(1):3-14.
late stage. Brain Inj. 2006 Apr;20(4):409-416. Smits M, Dippel DW, de Haan GG, et al. Minor head injury: guidelines for the
Cihangiroglu M, Ramsey RG, Dohrmann GJ. Brain injury: analysis of imaging use of CT—a multicenter validation study. Radiology. 2007 Dec;245(3):
modalities. Neurol Res. 2002 Jan;24(1):7-18:Review. 831-838.
Connor SEJ, Chaudhary N. Imaging of maxillofacial and skull base trauma. Vincent JL, Berré J. Primer on medical management of severe brain injury. Crit
Imaging. 2007;19:71-82. Care Med. 2005 Jun;33(6):1392-1399:Review.
Demaerel P, Casteels I, Wilms G. Cranial imaging in child abuse. Eur Radiol.
2002 Apr;12(4):849-857.
Gallagher CN, Hutchinson PJ, Pickard JD. Neuroimaging in trauma. Curr Opin
Neurol. 2007 Aug;20(4):403-409.
 chapter 13

Imaging of Spine Trauma

Alessandro Cianfoni and Cesare Colosimo

SPINE TRAUMA open-mouth odontoid necessary for C-spine clear-

ance. AP and lateral plain radiographs should be taken
Imaging: Why, Who, and How? without change of the patient’s position. If the cer-
(Computed Tomography: When, vicothoracic junction is not clearly visualized, addi-
Why, and How; Magnetic tional swimmer’s view or supine oblique views may
Resonance Imaging; When, Why, be obtained. Additional flexion–extension radiographs
and How; Computed Tomographic are of questionable use in the acute phase due to poor
Angiography) feasibility, technical reproducibility, and sensitivity and
the theoretical risk of causing additional spinal cord
Why Imaging? injury. (In rare cases, flexion–extension can be useful for
Spinal injuries are common sequelae of high-energy excluding delayed instability 2 to 4 weeks after trauma.)
acute traumas. The role of imaging is to establish the On the lateral view, attention should be directed toward
radiologic diagnosis, classify it, determine the stability assessing the integrity of the vertebral bodies and of four
and instability, evaluate the integrity of neural elements, parallel longitudinal lines (Figure 13-1): a line joining
and provide further radiologic evaluation when appro- the anterior margins of the vertebral bodies (anterior
priate. Given that spinal injuries can cause spinal cord spinal line), the posterior margin of the vertebral bodies
injury and major permanent disability, there is no con- (posterior spinal line), the interapophyseal line along
troversy regarding the need for accurate and emergent the posterior margin of the lateral masses, and the spi-
imaging assessment of the traumatized spine. nolaminar line joining the junction of the laminae with
the anterior margin of spinous processes. On the AP
Who Needs Imaging? view, a line along the tips of spinous processes should
It is important to judge the appropriate use of imaging be running straight downward (Figure 13-1). In cervical
in patients referred for spine imaging after trauma. A set and upper thoracic spine fractures, abnormal widening
of clinical and/or amnestic criteria can be very useful in of prevertebral or paravertebral soft tissue structures is
identifying patients who have an extremely low prob- significant. In the case of a patient who shows an abnor-
ability of injury and who consequently have no need for mal positioning of head and/or spine, repositioning for
imaging studies and those who are at high risk for hav- imaging is contraindicated until it is proven that the rea-
ing spinal injuries and therefore must undergo a thor- son for the abnormal position is not a life-threatening/
ough imaging evaluation of the spine. painful pathology.
Any trauma patient who is unconscious or intoxicated
in the emergency department, and therefore is not easily Problem Solving with Multidetector Computed
evaluated, needs spinal imaging to rule out significant Tomography
and possibly unstable spinal lesions. More controversial Until a few years ago, plain film radiography was the
debate exists about the selection criteria for imaging in initial imaging procedure in the evaluation of the spine
trauma patients who are fully alert. Most studies have in trauma patients. However, plain radiographs have
focused on cervical spine trauma, and the conclusions proved to have intrinsic low to medium sensitivity for
of those studies are routinely extrapolated to the thora- traumatic spinal injuries and suffer from additional
columbar spine injuries in the clinical practice. In alert technical limits in acute and immobilized patients.
(Glasgow Coma Scale score = 15) and stable patients, Some authors advocate the use of conventional radio-
the Canadian C-Spine Rule study established an accurate graphs, as a sole modality, only in low-risk patients
set of criteria to triage trauma patients who are at low risk and direct use of multidetector computed tomogra-
and therefore do not need spinal imaging (Table 13-1). phy (MDCT) in high-risk patients. Many other authors
now recognize MDCT as the preferred initial imaging
How to Image: Which Imaging Techniques procedure in acute (blunt) spinal trauma patients who
and Protocols Are Best? need imaging. MDCT is accurate and fast, and it can be
Problem Solving with Plain Film Radiography performed simultaneously with head, thoracic, and/or
In general, when plain film radiography is used for the abdominal computed tomography (CT), even using the
initial assessment, most institutions perform a mini- same raw data, in the polytraumatized patient, thereby
mum of three views: anteroposterior (AP), ­lateral, and reducing patient manipulation. Complex lesions can be

473
474 Section III  Problem Solving: Disease Categories

more clearly depicted using the reformatting and three- and possibly 3D volume-rendering images as well,
dimensional (3D) capabilities of MDCT. It is important which are especially useful at the craniocervical and
to note that the axial CT images alone may miss frac- atlantooccipital junctions. Evidence-based research has
ture lines that run parallel to the scans, compression established that MDCT improves patient outcome and
fractures, and subtle subluxations. Therefore, the whole saves money in comparison to plain film. Our institu-
diagnostic potential of MDCT should be used to advan- tion includes oblique reconstructions for the facet joints
tage (Figure 13-2), routinely obtaining multiplanar as well as the routine sagittal and coronal reconstruc-
reformatted thin section views for bone and soft ­tissues tions of the C-spine.

Problem Solving with CT Angiography

Table 13-1 Canadian C-spine Rule: Criteria to Triage Because blunt vascular injuries of the neck arterial ves-
Low-Risk Patients with Spinal Trauma Who Do Not sels associated with cervical spinal trauma are more
Need Imaging frequent than believed and can have devastating con-
A. Absence of high risk factors, including the following: sequences with cerebral embolism and infarction when
undiagnosed, we suggest obtaining the cervical spine
Age 65 years or older MDCT study just after injection of contrast agent bolus
Dangerous mechanism (fall from elevation of 5 feet/five stairs or used for other purposes in polytraumatized patients in
more; axial load to the head)
>100 km/h MVA, rollover or ejection MVA order to obtain simultaneous evaluation of the bony
Motorized recreational vehicle, bicycle collision spinal structures, and a CT angiogram of the neck to
Paresthesias in extremities rule out arterial dissection of the carotid and vertebral
B. Presence of low-risk factors, including the following: arteries.
Simple rear-end MVA (excluding pushed into oncoming traffic, Problem Solving with Magnetic Resonance
hit by bus or large truck, rollover, hit by high-speed vehicle)
Sitting position at admission Imaging
Ambulatory at any time since trauma Magnetic resonance imaging (MRI) can demonstrate
Delayed onset of neck pain the presence, location, and extent of spinal cord lesions,
No midline C-spine tenderness ligament and muscular injuries, disc herniation, epi-
C. Able to actively rotate neck 45 degrees bilaterally dural hematomas (EDHs), and bone marrow edema.
MRI should not be used as a primary screening tool
Patients who satisfy all of the A, B, C criteria are triaged as low
risk and do not need C-spine imaging. in spinal trauma, but it certainly should play a promi-
nent role in the thorough assessment of severe spinal
Modified from Stiell IG, Wells GA, Vandemheen KL, et al. The Canadian trauma to evaluate instability possibly caused by soft
C-spine rule for radiography in alert and stable trauma patients. JAMA.
2001;286(15):1841-1848. tissues injury and in any case of suggested spinal cord
MVA, Motor vehicle accident. or nerve root compromise. A quick assessment of the

A B
Figure 13-1 Assessment of C-spine radiographs in trauma. A: On this normal examination, the laterolateral view shows four uninterrupted
parallel longitudinal lines (black dotted lines). The line’s stepoff suggests dislocation. Thickness of the prevertebral soft tissues is <6 mm at C2
(short white arrow) and <22 mm at C5 (long white arrow). Increased thickness suggests hematoma due to rupture of the anterior longitudinal liga-
ment. B: Anteroposterior view showing alignment of the spinous processes (black dotted line). Misalignment suggests rotatory dislocation, such
as unilateral facet luxation.
 Chapter 13 Imaging of Spine Trauma 475

spine can be obtained by a set of T1-weighted and fat-

SECTION III
Acute Spinal Trauma Imaging
suppressed T2-weighted or short tau inversion recovery
(STIR) sagittal images to detect alignment abnormali- What Is the Role of Acute Spinal Trauma
ties, bone marrow edema (believed to be a sign of osse- Imaging in Problem Solving?
ous trabecular microfractures), ligamentous injuries, The role of acute spinal trauma imaging is to assess the
acute disc lesions and herniations, central canal com- spinal injury, to direct appropriate management, and
promise, cord contusions, compression, or transection. to predict neurologic outcome. The risk of mis(under)
The addition of a sagittal gradient-recalled echo (GRE) diagnosis is extremely high because of the possible life-
T2*-weighted sequence, which is sensitive to suscepti- long devastating sequelae. Awareness of the strengths
bility effects, allows the prognostically relevant distinc- and limitations of plain radiography, MDCT, and MRI
tion between hemorrhagic and nonhemorrhagic cord in the diagnosis of spinal injuries is fundamental, and
contusions. most often a multimodal imaging is required for best
practice.
Problem Solving with CT Myelography One single concept is worth keeping in mind when
CT myelography can only partially replace MRI in detect- imaging the acute spinal trauma: stability versus instability.
ing central canal compromise and spinal cord compres- Stability is the capacity of the spine to limit seg-
sion. In cases where MRI is unavailable, CT offers no mental motion so as to not risk damage to the neural
information on the cord parenchyma. CT myelography structures. Stability is provided by intact bony and liga-
also can have a role, after acute trauma management, mentous structures. The implication of clinical insta-
in rare cases of dural sac tears or unclear nerve root bility is the risk of delayed neurologic injury and the
­problems. need for surgical intervention to stabilize the spine.

Figure 13-2 Multidetector computed angiography (MDCT) of the C-spine. In the spine trauma setting, the full diagnostic potential of MDCT
should be exploited, obtaining thin axial cuts and multiplanar two-dimensional reformats, viewed with bone and soft tissue windows, as well as
multiple three-dimensional views, especially useful at the craniovertebral and C1–C2 junctions.
476 Section III  Problem Solving: Disease Categories

Despite ­numerous and complex classification systems, discs) and the content (spinal cord, nerve roots, cerebro-
Denis’ concept of stability based on the three columns spinal [CSF] spaces, meninges, vessels).
still holds valid. In the lower cervical segment of C3–C7
and in the thoracolumbar spine, support is provided by Which Lesions Are Present? What Is the
three columns (Figure 13-3). Mechanism of Injury? Is There Instability?
The anterior column consists of the anterior vertebral Traumatic spinal lesions are represented by fractures,
bodies, the anterior annulus fibrosus, and the anterior dislocations, ligamentous disruption, disc injury, acute
longitudinal ligament. The middle column consisted disc herniations, and EDHs, often combined.
of the posterior vertebral bodies, posterior longitudinal Fractures and dislocations usually occur based on a
ligament, and posterior annulus fibrosus. The poste- single predominant mechanism of injury. The six major
rior column includes the posterior bony elements, the mechanisms of injuries are (1) hyperflexion, (2) simul-
ligamenta flava, and the posterior ligaments. A spinal taneous hyperflexion and rotation, (3) hyperextension,
lesion is considered unstable if it involves the middle (4) simultaneous hyperextension and rotation, (5) ver-
column, which is considered the most crucial for spinal tical compression, and (6) lateral flexion. The injuries in
stability. Middle column lesions are most often associ- each class have characteristic radiologic abnormalities,
ated with lesions of the adjacent anterior or posterior which are more or less specific for that group.
column, so lesions involving two or more columns are nn Hyperflexion implies distraction of posterior ele-
considered unstable. With the more widespread use of ments and compression of the anterior columns. It
MR in acute spinal trauma, it is not too uncommon can result in compression fractures, which involve the
to encounter extensive ligamentous lesions on STIR anterior column and therefore are stable, or burst frac-
images, in absence of bony fractures. In these cases, tures, which involve the anterior and middle columns
although no rigid rules are given, a little flexibility in and therefore are considered unstable. Hyperflexion
thinking is required. Ligamentous disruption involving causing significant distraction of the posterior ele-
all three columns at one level certainly is considered ments results in severe instability, with anterior luxa-
as an unstable lesion. However, most spinal surgeons tion, facet dislocation, and flexion teardrop fractures.
do not feel quite comfortable fusing a spine with only nn Hyperextension involves distraction of the anterior
two-column soft tissue injury and will ask for further column and compression/rotation/translation of the
dynamic imaging such as flexion-extension x-ray films middle and posterior columns.
to assess stability. nn The addition of rotational forces to both hyperflexion
and hyperextension results in more complex patterns
The Important Problem-Solving Questions of injury.
Imaging a traumatized spine implies answering a set of With minor modifications due to anatomic and biome-
important questions regarding the status of the spinal chanical differences, the same principles apply to all the
supporting structures (bony elements, ligaments, and spine segments in the lower C-spine and thoracolumbar

A B
Figure 13-3 Denis’ three-column stability concept. Delineation of the three columns over axial (A) and three-dimensional lateral views
(B) of lumbar vertebrae. The middle column (red) plays a crucial role in the stability of the spine from C3 to L5. Fractures of the middle column
are rarely isolated and usually are associated with anterior or posterior column fractures, featuring unstable lesions.
 Chapter 13 Imaging of Spine Trauma 477

spine. The craniovertebral junction (CVJ) has specific Atlantoaxial Dislocation (C1–C2) (Figure 13-5)

SECTION III
peculiarity and therefore is treated separately. Caused by severe hyperextension, implies ligamentous
disruption, especially of the transverse ligament of the
Craniovertebral Junction (C0–C2) dens, resulting in widened distance between the anterior
The CVJ is a specialized structure with peculiar anatomy arch of C1 and the dens (>3 mm in adults). STIR images
that results in patterns of injuries specific to this region. show extensive soft tissues injuries. The odontoid tip
The CVJ is formed by the atlantooccipital and atlantoax- can be fractured.
ial joints, and it is well adapted to provide a remarkable
range of motion, with most of neck rotation occurring Atlantoaxial Rotation (C1–C2) (Figure 13-6)
at the C1–C2 articulation. The CVJ is the most fre- The atlas loses articular congruence with the lateral artic-
quently injured spine segment in children, but because ular masses of C2, there is asymmetric articular distance
of the relatively large spinal canal diameter at this at C1–C2, the odontoid is in an asymmetric position
level, neurologic deficits occur only in the most severe with respect to the anterior arch of C1, and the C1 spi-
dislocations. nous process is rotated. The luxated joints are locked,
so the patient presents with traumatic torticollis, and
Atlantooccipital Dislocations (C0–C1) the asymmetry of joints, dens, and spinous process does
(Figure 13-4) not correct with head rotation. Normal patients scanned
Look for increased basion–dens tip distance (>12 with the head tilted even mildly on one side can show
mm), increased Powers ratio, occipital condylar frac- a significant degree of mobility at this joint on CT. Such
tures, misalignment of atlas and occipital condyles on articular excursion should not be diagnosed as an injury.
reformatted coronal CT images, prevertebral soft tissue Trying to position patients in the scanner with head and
hematoma at C2, edema in the alar ligaments on sagit- shoulder straight and aligned, multiplanar reformatting,
tal or coronal STIR MRI, and disruption of the tectorial and, when needed, a repeat scan with contralateral head
membrane on sagittal T2-weighted MRI. rotation can prevent overdiagnoses.

A B C

D E F
Figure 13-4 Hot spots for assessment of atlantooccipital dislocations. A: On the sagittal view, basion–dens tip distance should not exceed 12
mm, and Powers ratio (ab/cd) should not exceed 1. B: Coronal view showing the distance between the dens and the C1 lateral masses (double
arrows) and the articular alignment between C1 and C2 lateral masses (black dotted lines). C: Attention should be directed to note condylar frac-
tures (white arrow). D, E: Magnetic resonance imaging fat-suppressed T2-weighted images showing ligamentous injuries revealed by high signal
in the predental space and along the alar ligaments (white arrows) and along the anterior longitudinal ligament in the prevertebral soft tissues
(arrowheads). F: Laterolateral radiograph of a complete atlantooccipital dislocation revealed by loss of articulation at the craniovertebral junction
(double arrow). (Courtesy of Dr. A. Leone, Rome, Italy.)
478 Section III  Problem Solving: Disease Categories

A B C

D E F
Figure 13-5 Atlantoaxial dislocation. As a result of severe extension injury, there is fracture of the odontoid tip (arrowheads in D and E) and
rupture of the transverse ligament of the dens, revealed on plain films and computed tomography by increased anteroposterior distance between
the arch of C1 and the dens (arrow in D) and by asymmetric lateral C1–C2 dislocation (double arrow in B). The full degree of C1–C2 dislocation
is best appreciated on the subvolume axial maximal intensity projection (MIP) superimposing the C1–C2 junction (C). Magnetic resonance
imaging shows high T2 signal on the STIR image at the atlantoaxial joint (arrow in E), accompanied by prevertebral hematoma, extending from
the clivus to C7, suggesting rupture of the anterior longitudinal ligament, and high T2 signal in the interspinous ligaments at C1–C2, indicating
further soft tissue injury.

A B C
Figure 13-6 Atlantoaxial rotatory luxation. Axial subvolume maximal intensity projection (MIP) (A) and three-dimensional (3D) VR views
(B, C) of the C1–C2 junction clearly showing rotatory luxation at C1–C2, with increased predental distance and loss of articular congruence
between the C1 and C2 lateral masses (arrowhead in B). There is striking misalignment of the C1 and C2 spinous processes (arrows in C).
 Chapter 13 Imaging of Spine Trauma 479

C1 Fractures with resultant bilateral fractures of the pars interarticu-

SECTION III
A burst fracture (Jefferson fracture) is the result of axial laris (C2 vertebra is only cervical vertebra with a true
loading with bilateral outward displacement of the lat- pars interarticularis); there is anterior displacement of
eral masses of C1. This injury can be diagnosed by rec- the anterior portion of C2 to C3 (Figure 13-9). This frac-
ognizing the fractures in both the anterior and posterior ture is often associated with spinal cord injury.
arches of C1 and on coronal images by the increased
distance between the lateral masses of C1 (Figure 13-7). What to Look for on CVJ Acute Trauma
Separation of the lateral masses from the dens greater Imaging?
than 7 mm implies atlantoaxial instability due to tear- nn On axial thin CT sections: Look for obvious fracture lines
ing of the transverse ligament. An isolated fracture of of the occipital condyles, the atlas arches, the C2 verte-
the posterior arch of C1 may result from hyperexten- bral body, and the posterior elements. Check the mid-
sion with impaction of the posterior arch of C1 between line position of the spinous process of C1 and the central
the occiput and C2. This injury is distinguished from position of the odontoid to the anterior arch of C1.
C1 burst fracture by involvement of only the posterior nn On sagittal reformatted CT images: Look for the
arch. An isolated fracture of the anterior arch of C1 is basion–odontoid distance, the Powers ratio, the C0–
less common. It also results from hyperextension with C1 joints, the integrity of the dens and the C2 pars
avulsion of the attachment of the anterior spinal liga- interarticularis, and the distance between dens and
ment. The small avulsed bone fragment is visible ventral C1 anterior arch. On soft tissue window images, rule
to the anterior arch of C1. out gross prevertebral hematomas and central canal
compromise.
C2 Fractures nn On coronal reformatted CT images: Look for occipi-
C2 fractures can involve the dens, the body, the pars tal condyle fractures, splaying of C1 lateral masses,
interarticularis, and the posterior arch. Dens fractures uncovering of C2 lateral masses by exaggerated and
are frequently observed in elderly patients and are clas- locked atlas rotation, and correct midline position of
sified according to a scheme proposed by Anderson and the dens.
D’Alonzo (Figure 13-8). They are commonly classified nn On MRI: STIR or fat-suppressed fast spin-echo (FSE)
into type I, rare, involving the dens tip, to be differenti- T2-weighted images are useful for detecting soft tis-
ated from an os odontoideum; type II, most common, sue edema suggesting ligamentous disruption and
consisting of a fracture through the base of the dens at prevertebral hematomas along the anterior longitu-
its junction with the body of C2, unstable, with a high dinal ligament. Assess the bulbomedullary junction
incidence of nonunion if not surgically fused; and type and the cervical spinal cord for extrinsic compression
III, involving the upper body of C2. The body of C2 can and cord injuries with T2- and T2*- weighted images.
also be involved in burst fractures resulting from hyper- Although any severe cervical spine trauma harbors the
flexion or axial loading forces. Traumatic spondylolysis risk of vertebral and carotid artery dissection even with-
of C2 (hangman’s fracture) is caused by hyperextension out evidence of fractures or direct arterial injury, when a

A B
Figure 13-7 C1 burst fracture (Jefferson fracture). A: Axial computed tomographic image through C1 showing bilateral fractures of the anterior
and posterior arches of the C1 ring (white arrows). B: Coronal reformatted two-dimensional view showing increased distance between the C2
dens and the left C1 lateral mass (double pointed arrow), suggesting unstable transverse ligament rupture, increased distance between the occipital
condyle and the C1 lateral mass on the left (arrowhead), and loss of articular congruence at the C1–C2 lateral masses (arrows). There is also a right
C2 lateral mass fracture.
480 Section III  Problem Solving: Disease Categories

A B C

D E F
Figure 13-8 Odontoid fractures following the scheme proposed by Anderson and D’Alonzo. A: Thin fracture line of the dens tip (arrowhead)
featuring a nondisplaced type 1 fracture. B: Aligned type 2 fracture. C: Displaced type 2 fracture. Both B and C involve the base of the dens.
D–F: Multiplanar views of a type 3 odontoid fracture coursing through the body of C2.

fracture is seen involving the vertebral artery transverse injury and facet dislocation. A simple wedge fracture
foramen, arterial dissection absolutely needs to be ruled involves only the anterior column, whereas a complex
out with vascular imaging (CT angiography or MR angi- fracture involves the middle column and can have a
ography and fat-suppressed axial T1- weighted imaging, retropulsed posterior vertebral wall (Figure 13-11).
or digital subtraction angiography) (Figure 13-10). nn Posterior ligament disruption is best shown by MRI
on STIR and fat-suppressed FSE T2- weighted images
Lower C-Spine (C3–C7) and Thoracolumbar as ill-defined high T2 signal or fluid collection in the
Spine ligaments between the spinous processes, adjacent to
Hyperflexion Injuries. These injuries, which are facet joints, along the posterior margins of the verte-
especially common in divers, are characterized by bral bodies.
abnormal widening between adjacent posterior ele- nn Facet dislocation requires greater forces, especially
ments, variable degree of kyphotic angulation at the in the thoracolumbar region, and consists of ante-
level of injury, and wedge-shaped deformity of the ver- rior luxation of the inferior articular process of the
tebral body. They include wedge fractures, disruption of upper vertebra above and in front of the superior
the posterior ligaments (interspinous ligaments, facet articular process of the lower vertebra. It is associated
capsules, and posterior longitudinal ligament), bilateral with facet capsules, posterior longitudinal ligament,
facet joint dislocations, and teardrop fractures. The dif- annulus fibrosus, and interlaminar and interspinous
ferent combination of these elementary lesions depends ligament disruption. On axial images it is revealed by
on the magnitude of the lesional forces and determines the “naked facet” sign, whereas reformatted sagittal
the severity and the stability of the injury. images give the impression that the facets of the upper
nn Wedge-shaped fracture is caused by impaction fracture vertebra have jumped over the inferior ones, which
of the superior end plate, with integrity of the infe- remain uncovered. The jumped facet can encroach
rior end plate and height loss of the anterior column. on the articular pillar (“perched facet”) or be lodged
If height loss is less than 50%, the wedge fracture is in the neural foramen (“locked facet”). Despite their
considered stable; if height loss is greater than 50%, denomination, when bilateral, these injuries are
it usually is associated with posterior ligamentous unstable (Figure 13-12).
 Chapter 13 Imaging of Spine Trauma 481

SECTION III
A B

C D
Figure 13-9 Traumatic C2 spondylolysis (hangman’s fracture). This fracture involves the C2 pars interarticularis bilaterally (arrowheads in
B and D) and causes mild C2–C3 anterolisthesis (arrow in C). Due to the frequent compromise of the C2 vertebral artery foramen, computed
tomographic angiogram is recommended for these fractures. Laterolateral plain film (A) fails to clearly identify this extremely important finding.

A B C
Figure 13-10 Neck computed tomographic angiogram (CTA) in cervical spinal trauma. In this type 2 odontoid fracture associated with a
comminuted left C2 lateral mass fracture, CTA shows compression and narrowing of the left vertebral artery in its bony foramen (arrow in A and
arrowhead in B), with preserved patency (C) and no clear signs of vertebral dissection.
482 Section III  Problem Solving: Disease Categories

A B

C D
Figure 13-11 Wedge fractures. Traumatic injuries are often more complex than their classification systems. A–D: Wedge fracture of the T-spine
with anterior vertebral body height loss of about 50% and middle column involvement in the form of a retropulsed fragment (arrow in B) indent-
ing the central canal and possibly compressing the spinal cord.

nn Teardrop fracture consists of a large triangular frac- when the spine is flexed about a fulcrum point, such as a
ture fragment arising from the anteroinferior margin car lap seatbelt, and is defined as a horizontally oriented
of the upper vertebral body, associated with posterior fracture that passes through the spinous process, lami-
ligament complex disruption. Flexion teardrop frac- nae, and vertebral body. A horizontal disruption involv-
tures are the result of greater magnitude forces and ing the intervertebral disc or posterior ligaments, rather
usually are complicated by middle column fractures than the vertebral body or posterior bony elements, is
and retropulsion of bony fragments into the spinal considered a variation of the Chance fracture (Figure
canal (Figure 13-13). 13-14).

What Are the Typical Variants of Hyperflexion Hyperextension Injuries

Injuries that Occur at Different Levels? Extension injury of the cervical and thoracolumbar
Clay shoveler’s fractures is a stable fracture of the spi- spine results in backward rotation or translation of the
nous process seen in the cervical spine or at the cervico- vertebra in the sagittal plane. It often results from an
thoracic junction. anterior impact on the mandible, face, or forehead, or
Chance fracture is an unstable fracture that occurs from sudden deceleration. They are less frequent than
nearly exclusively at the thoracolumbar junction. It is flexion fractures. These injuries may result in either
thought to be the result of distractive forces generated hyperextension dislocation or hyperextension teardrop
 Chapter 13 Imaging of Spine Trauma 483

SECTION III
E F

G
Figure 13-11, cont’d E–G: Another T-spine wedge fracture with anterior vertebral body height loss less than 50% but with complex middle
column posterior longitudinal ligament disruption and retrolisthesis (arrowhead in E), posterior column fractures (arrows in E and F), and liga-
mentous injury with facet capsule disruption (arrowhead in F).

fracture, almost invariably associated with intervertebral Hyperextension teardrop fracture is an avulsion frac-
disc disruption. ture of the anteroinferior margin of the vertebral body
Hyperextension dislocation is a disruption of the lig- caused by excessive stress on the anterior longitudinal
aments between adjacent vertebrae, including the ante- ligament. The fracture fragment can be distinguished
rior longitudinal ligament, annulus fibrosus, and facet from the avulsion fracture of hyperextension dislocation
capsular ligaments. Because there may be no fracture, by the obliquity of the fracture line (approximately 45
the only clue on radiographs and CT may be thicken- degrees from vertical) and the relatively greater height
ing of the prevertebral soft tissues, which is better seen of the fragment. In contrast to hyperflexion teardrop
on MRI. This injury is frequently associated with severe fractures, hyperextension teardrop fractures show no
spinal cord contusion, especially in patients with preex- evidence of posterior ligament disruption.
isting degenerative changes and central canal stenosis.
Hyperextension dislocation injury is often accompanied Vertical Compression Injuries
by an avulsion fracture of the anteroinferior margin of Axial loading injury of the cervical and thoracolumbar
the affected vertebral body, caused by traction of the spine results from an impact to the top of the head when
annulus fibrosus. This has an almost horizontally ori- the spine is straight and vertical compressive forces are
ented fracture line. transmitted through the intervertebral disc with radial
484 Section III  Problem Solving: Disease Categories

A B C

D E
Figure 13-12 Facet dislocation. A, B: C6–C7 facet dislocation causing severe anterior spondylolisthesis, canal narrowing, and very likely spi-
nal cord compression. There is evident discontinuity of the anterior and posterior spinal and spinolaminar lines on the midline sagittal image
(A) suggesting extensive three-column ligamentous injury, whereas the off-midline sagittal image (B) shows the “jumped facet” (arrow) that
encroaches over the articular pillar, featuring the so-called perched facet. C: Another example of facet dislocation associated with a facet fracture
(arrow). D, E: Thoracic facet dislocation example where the jumped facet is completely dislodged and locked in the neuroforamen (arrow in D),
whereas the axial image shows the “naked facet” sign (arrows in E) and the prevertebral hematoma (arrowheads in E). This facet dislocation is
associated with a wedge fracture as well.

outward forces generated in the vertebral body. Typi- ­ islocation. Lateral force vectors may lead to isolated
d
cal representative example is the burst fracture in the fractures of the uncinate processes, lateral wedge, and
lower cervical and thoracolumbar spine. Burst fractures lateral burst fractures. Combined extension and rotation
consist of a vertically oriented fracture of the vertebral forces may result in pillar or pedicolaminar fractures.
body with lateral dispersion of the fracture fragments
(Figure 13-15). The posterior wall of the vertebral body Disc Injuries
is disrupted, which does not occur with wedge fractures, Disc disruption is demonstrated by MRI T2-weighted
and the distance between the pedicles is widened. Usu- images as increased T2 signal in the intervertebral space,
ally, there are associated fractures in the posterior ele- more often as a rim lesion near the anterior vertebral rim.
ments. Burst fractures are either stable or unstable. The If the posterior annulus is also disrupted, an acute trau-
encroachment of the spinal canal may lead to cord inju- matic disc herniation, characterized by high T2 signal and
ries in up to 50% of cases. mass effect on the spinal cord, may occur (Figure 13-16).
Disc injury is caused by distraction and shearing in sudden
Other Mechanisms extension, in which case both the posterior disc and the
Less common mechanisms of injury may lead to rec- facets are compressed, causing disc contusion or hernia-
ognized fracture patterns. A combination of flexion tion, facet hemarthroses, or fractures of articular processes.
and rotational forces can result in a unilateral facet Traumatic disc lesions also occur after flexion injuries.
 Chapter 13 Imaging of Spine Trauma 485

SECTION III
A B

C D
Figure 13-13 Flexion teardrop fracture. Hyperflexion forces of great magnitude caused a wedge deformity and a fracture of a large triangular
portion of the anteroinferior portion of the vertebral body (arrowheads). There is also evidence of disruption of the posterior ligamentous complex
with facet subluxation. This degree of kyphotic deformity caused a spinal cord injury.

Ligamentous Injuries At times the pattern of bone marrow edema further

Ligamentous injuries can occur even in absence of clarifies the injury mechanism or leads to a retrospective
detectable fractures. They are suspected on MRI by direct identification of subtle fractures originally missed on CT
visualization of a gap or by an increased signal in the (Figure 13-17).
ligament or the surrounding structures on STIR images
or fat-suppressed FSE T2-weighted images, which might Whiplash Injuries
represent edema or acute hemorrhage (Figure 13-17). Whiplash is one of the most common mechanisms of
However, the sensitivity of MRI in detecting ligamen- injury to the cervical spine and cord. The term whiplash
tous injuries is relatively low. describes the manner in which a head is moved sud-
denly to produce a sprain in the neck.
Bone Contusions/Microfractures Whiplash has become a popular term commonly
Bone marrow edema, suggesting bone bruises or micro- used to refer to a syndrome following a neck sprain.
fractures, usually is revealed by MRI in patients with sig- Evidence suggests that whiplash injuries are real and
nificant spinal trauma as focal areas of abnormal high are manifested by symptoms consistent with the ana-
signal on STIR or fat-suppressed T2-weighted images tomic lesion sustained and that they are a potential
against the dark background of normal bone marrow. cause of significant impairment. The diagnosis of a
486 Section III  Problem Solving: Disease Categories

A B C D
Figure 13-14 Chance fracture. A, B: Horizontally oriented fracture at the thoracolumbar junction coursing in the axial plane through the poste-
rior and anterior bony elements (arrows). (Courtesy Drs. Z. Rumboldt and D. Nissman, Charleston, SC.) C, D: Variant of Chance fracture, with the
horizontally oriented fracture traversing the posterior bony elements (arrowhead in C) and the disc space, disrupting the ligamentous structures,
and causing anterior listhesis, central canal narrowing, and very likely spinal cord injury. The sagittal images clearly suggest that this type of injury
occur with hyperflexion at the site of a fulcrum, as occurs with use of a pelvic seatbelt.

A B C
Figure 13-15 Burst fracture. Multiplanar computed tomographic views showing the striking outward displacement of multiple vertebral frac-
ture fragments due to vertical compression force. There is a large retropulsed bone fragment occupying the central canal (arrow in B) and volumi-
nous soft tissue hematoma in the perivertebral space. (Courtesy of Dr. A. Leone, Rome, Italy.)

whiplash injury is determined by the history pro- distraction and posterior facet compression lesions.
vided, the mechanism of injury, the symptoms, and Therefore, some research is focused on detecting disc–
the physical findings on examination. Patients usually endplate lesions, facet capsule disruption, or facet
report nonradicular upper extremity pain, neck pain, microfractures.
headache, paresthesia, vertigo, and fatigue. The role of
medical imaging in the evaluation of whiplash injuries What About the Spinal Content
remains to be determined. One of the key problems (Spinal Cord and Nerve Roots)?
in imaging whiplash-injured patients is the lack of The discussion on the possible mechanisms and the
knowledge of the underlying pathology of the trauma. appearance of trauma of the spinal column is finalized
Recent studies suggest that a whiplash injury is not a to rule out injury or risk of injury of what really matters:
hyperextension/hyperflexion injury but a combined the content of the spinal supporting structures, consist-
axial loading and rotation resulting in anterior discal ing of the neural structures, spinal cord, and nerve roots.
 Chapter 13 Imaging of Spine Trauma 487

SECTION III
A

C D
Figure 13-16 Traumatic disc injuries. A, B: Hyperextension injury characterized by multiple vertebral fractures on computed tomography
and soft tissue injuries on magnetic resonance imaging, such as ligamenta flava and interspinous ligament disruption (arrow in B) and high T2
signal in the C2–C3 disc (arrowhead in B), with retrolisthesis and cord compression. Anterior longitudinal ligament injury is suggested by the
retropharyngeal hematoma, but the posterior longitudinal ligament is stretched but not torn, and is visualized as a thin black line at the posterior
disc margin on B; no disc herniation is seen. C, D: Large T2-hyperintense C4–C5 disc extrusion compressing the spinal cord following a rear-end
motor vehicle collision. High T2 signal of the disc fragment indicates a high water content of this extrusion, probably coming directly and acutely
off the nucleus pulposus.

How Can the Neural Structures Be Injured? within the cord may cause signal loss on T2*-weighted
The spinal cord and the nerve roots can be traumatically images. Adding a sagittal GRE T2*-weighted sequence
injured by transection, compression, contusion, stretching, to the imaging protocol is helpful in assessing more reli-
and, much more rarely, by direct vascular compromise. ably the prognosis of spinal cord injuries. The spinal cord
edema caused by contusion usually is focal, at the site of
What Do Traumatic Spinal Cord Lesions Look the injury, but in most severe injuries edema and swell-
Like? ing can extend to upper and lower adjacent levels. In fol-
MRI is the imaging method of choice for demonstrat- low-up studies the edema can gradually resolve, usually
ing acute intramedullary abnormalities in traumatized accompanied by improvement of clinical conditions, or it
patients, such as medullary transection, contusion, and can evolve in a progressive ascending myelopathy, present-
hemorrhage (Figure 13-18). Contusion of the cord is ing as an enlarged cord with high signal on T2-weighted
best seen on T2-weighted images as a high-signal lesion imaging several segments superior to the original injury
within the cord, with variable mass effect due to swelling. site. In the subacute phase, the spinal cord lesion can also
T1-weighted images show little or no signal abnormality. show abnormal enhancement after contrast injection.
When hemorrhagic cord contusion is present, the prog- In some cases the swollen and enlarged cord appears
nosis is much more unfavorable. In these cases, bleeding compressed in a central canal that would otherwise be
488 Section III  Problem Solving: Disease Categories

A B

C D
Figure 13-17 Soft tissue injury and bone bruise. A: Sagittal STIR image of patient with no C-spine fractures on computed tomography showing
extensive soft tissue injuries, with high signal in the prevertebral/retropharyngeal space (arrowheads), suggesting anterior longitudinal ligament
(ALL) lesion with hemorrhage or edema, and along the interspinous and supraspinous ligaments (arrows), suggesting ligamentous disruption.
B: Another case of C-spine trauma where dislocation and disc injury at C7–T1 is associated with ALL injury (arrowhead) and striking posterior
ligamentous complex injury (arrows). C, D: High T2 signal is noted on STIR sagittal image in the bone marrow of the C3 vertebral body and
spinous process (arrows in C), so-called bone bruising, in correspondence with subtle fractures as seen on computed tomography (arrows in D).

of normal width. Nevertheless, surgical decompression acute fashion as the so-called central spinal cord syndrome
in such instances should be considered given the risk of or acute traumatic central cord syndrome, a reversible
further spinal cord damage caused by secondary com- or partially reversible paralysis affecting the arms more
promise of the cord vascular supply. than the legs, bladder dysfunction, and variable sensory
loss. This syndrome correlates with microscopic features
What is SCIWORA? of white matter injury revealed by loss of axons in the
The acronym SCIWORA stands for “spinal cord injury lateral corticospinal tracts. SCIWORA can also pres-
without radiographic abnormalities.” It is a type of spi- ent with delayed onset of neurologic symptoms, up to
nal cord injury that occurs in the absence of fractures or 4 days after injury.
dislocations. The lesion is usually due to contusion or
cord stretching and is more commonly seen in infants Do Epidural and Subdural Hematomas Occur
and young children as a consequence of their vertebral in the Spine As Well?
column elasticity and vulnerability to deforming forces, The answer is yes, although subdural hematomas of
and in elderly patients with preexisting spinal narrow- the spine are exceptionally rare. EDHs, on the other
ing (Figure 13-19). SCIWORA can present clinically in hand, occur quite frequently in the presence of vertebral­
 Chapter 13 Imaging of Spine Trauma 489

SECTION III
A B C D

E F G H
Figure 13-18 Spinal cord injuries. A, B: Spinal cord nonhemorrhagic contusion due to C5–C6 osteophyte and disc extrusion, with spinal cord
swelling and faint and ill-defined high T2 signal. The cord is encroached, but there is no true cord compression. The posterior subarachnoid space
is patent (arrowhead in A). Gradient-recalled echo (GRE)-T2* image, which is sensitive to blood products, does not show any cord hemorrhage. C,
D: Cord contusion with different degree of cord compression. In both cases there is vertebral dislocation narrowing the central canal and distort-
ing the spinal cord, which also shows high T2 signal, consistent with compressive myelopathic edema (arrows in C and D). E, F: Following cord
contusion, the cord shows abnormal high T2 signal (E), is swollen, and appears compressed due to the effacement of the subarachnoid spaces, but
there is no true central canal narrowing. F: GRE T2*-weighted image showing extensive hemorrhage within the cord, visible as low signal, which
makes the prognosis more dismal. G, H: Two examples of very severe cord injury, with extreme compression (G) and complete cord transection
(H), indicated by the cerebrospinal fluid–filled gap along the cord (arrow in H).

fractures, but usually they are of venous origin. MRI is the fat-suppressed sequences. Because the dura mater is not
imaging method of choice to demonstrate EDH, although firmly attached to the walls of the bony canal as it is to
it also should be actively ruled out on the admission CT the calvarium, the typical biconvex shape of an intracra-
scan images viewed with a soft tissue windowing setting. nial EDH is not observed in the spine, and the EDH can
The epidural collection on MRI (Figure 13-20) usually is extend ­circumferentially around the dural sac, possibly
isointense to hyperintense on T1-weighted images and causing severe compression of the neural structures. On
hyperintense to ­hypointense on T2-weighted images. It good-quality sagittal or axial T2-weighted images, a thin
does not enhance after contrast administration and its dark line representing the dura is usually appreciable
signal does not suppress; therefore, it is more evident on between the hemorrhagic collection and the CSF.
490 Section III  Problem Solving: Disease Categories

alternative CT myelography. On these images the nor-

mal nerve filaments are directly visualized, whereas the
avulsed filaments are either absent or detached from the
spinal cord. Indirect signs of nerve root avulsion also
can be observed on less sophisticated axial T2-weighted
MRI, such as contralateral displacement of the spinal
cord in the central canal due to traction from the intact
nerve roots, and the appearance of traumatic meningo-
celes and focal extradural pooling of CSF, often in the
foramen or in the paraspinal soft tissues, caused by nerve
root sleeve disruption (Figure 13-21). Brachial plexus
injuries are best imaged in the coronal plane through
fat-suppressed or STIR T2-weighted images. These inju-
ries are usually imaged in the subacute phase, and it is
not uncommon to see abnormal contrast enhancement
of the avulsed nerve roots or of the injured brachial
A B plexus elements (Figure 13-22).

What to Look for on Acute Spinal Trauma

Imaging
Obtain multiplanar reformatted thin CT sections of the
spine.
Check different views for CVJ, general spinal alignment,
vertebral body height, central canal width, facet
joints, fractures, with particular attention to integrity
of walls of posterior vertebral bodies, and retropulsed
bone fragments.
Use soft tissue window settings to look for soft tissue
density masses in the central canal, such as trau-
matic disc herniations and EDH, which may cause or
worsen the associated spinal cord injury, and in the
prevertebral space, such as prevertebral hematomas.
If a fracture or dislocation is present, estimate the cen-
tral canal compromise and the possible related injury
to the spinal cord, as well as the presence of possible
vascular injuries, especially in cervical spine fractures
involving the foramen transversarium, which consti-
C D tutes the bony canal for the vertebral arteries.
If a facet dislocation is present, assess facet fractures
Figure 13-19 SCIWORA (spinal cord injury without radiographic that could interfere with attempts at reduction. Try to
abnormalities). Preexisting degenerative conditions, such as disc–
osteophyte complexes, disc herniations, and central canal stenosis,
identify a lesion pattern that suggests a specific mech-
may cause spinal cord injury with minor spinal trauma, even in the anism of injury.
absence of evident acute traumatic fractures or dislocations. A, B: Par- Judge stability versus instability of the different spine
tially calcified posterior disc–osteophyte complex (arrows in A and lesions.
B) is a quite common and apparently benign degenerative finding, Be aware that degenerative changes, such as posterior
but it can represent a risk factor for SCIWORA in the trauma setting.
C, D: Two cases of spinal cord contusion (arrowheads in C and D) with osteophytes and central canal stenosis, increase the
no radiographic evidence of fracture or dislocation in trauma patients likelihood of serious spinal cord injuries even with
with preexisting congenital (C) or degenerative (D) spinal stenosis. minor spine trauma.
If neurologic symptoms or signs are present, an emer-
gent MRI study is warranted to assess spinal cord
How to Identify Nerve Root Avulsions, Particularly lesions or compression.
If There Is a Clinical Problem? If a spinal cord lesion is present, a severe compression
Nerve root avulsion from the cord can occur at the cer- needs to be differentiated from a complete transection.
vical level and usually occurs in conjunction with bra- Although the prognosis is sometimes equally grim,
chial plexus injuries due to traction forces on the arm compression of a nontransected spinal cord poses an
or the shoulder. Nerve root avulsion is often associated indication for emergent decompressive surgery.
with nerve root sleeve disruption. The best imaging tech- Detect signs of bleeding in the spinal cord, which wors-
nique to demonstrate nerve root avulsion is MRI with ens the prognosis of spinal cord injuries.
3D acquisition producing strongly T2-weighted thin sec- On axial T2-weighted images of the cervical spine, do
tions, so-called MR myelography sequences such as 3D-CISS not miss indirect signs of nerve root avulsion, such as
(constructive interference in steady state)/3D-FIESTA traumatic meningoceles and off-center contralateral
(fast imaging employing steady-state acquisition), or position of the spinal cord in the canal.
 Chapter 13 Imaging of Spine Trauma 491

SECTION III
A B

C D
Figure 13-20 Epidural hematoma. Fat-suppressed T2-weighted (A), nonenhanced T1-weighted (B), gadolinium-enhanced fat-suppressed
T1-weighted sagittal image (C), and fat-suppressed T2-weighted axial image (D) showing an acute traumatic compression fracture of T11 vertebral
body (arrows in A–C), complicated with an epidural hematoma (arrowheads in A–D) occupying the right posterior half of the central canal and
compressing the spinal cord (arrow in D). The hematoma is of heterogeneous high and low T2 signal, isointense to hyperintense on T1, and shows
no enhancement after contrast. The cord appears displaced and compressed, and displays high T2 signal consistent with edema. On the axial
image (D), the inward displaced dura is visible as a thin dark line between the hematoma and the spinal cord.

Traumatic disc herniations and EDHs are shown on MRI retrospectively diagnosing subtle fractures originally
to better advantage and are important findings, often missed on CT.
representing surgical indications.
Use MRI to assess soft tissue injuries, thereby increasing What Are the Possible Pitfalls in Spinal Trauma
the accuracy of assessment of stable versus unstable Imaging?
spinal lesions. nn Subtle patient movements during MDCT scanning,
On T2-weighted sagittal images, check for hyperintense such as breathing, shaking, or coughing, can originate
signal in the discs, which could reveal traumatic disc false images of fracture or dislocation when reformat-
injuries. ted on different planes (Figure 13-23). Looking at the
On STIR images, look for high-signal injuries of skin contours and double checking the axial source
the ligaments for prevertebral and paravertebral images help avoid wrong diagnosis and, in the worst
­hematomas and for bone marrow edema. Bone case scenario, unnecessary interventions.
marrow edema, also called bone bruise, is a sign of nn MR T2-weighted sagittal images are usually the most
trabecular microfractures, useful in further clarify- informative of spinal cord status. High T2 signal in
ing the injury mechanism and sometimes helpful in the spinal cord is worrisome for cord lesions, edema,
492 Section III  Problem Solving: Disease Categories

B C
Figure 13-21 Cervical nerve root avulsion due to delivery trauma. T2-weighted axial image (A) and computed tomographic myelogram (B)
reveal an extradural foraminal cerebrospinal fluid collection, representing a traumatic pseudomeningocele (arrows on A, B and C) following root
sleeve laceration. The dural margins are clearly visible. The intradural nerve roots are not visualized ipsilaterally but are individually visualized
contralaterally (arrowheads on B and C). Note the slightly off-center and rotated position of the spinal cord (B) due to asymmetric traction by the
intact nerve roots toward the normal side. (Courtesy Dr. Z. Rumboldt, Charleston , SC.)

A C
Figure 13-22 Brachial plexus traumatic injuries. A: T2-weighted fat-saturated coronal image showing striking swelling and high T2 signal of
the right brachial plexus (arrowheads) in a patient with traumatic distraction injury of the right shoulder and monoplegia of the right upper limb.
B, C: More subtle case showing mild asymmetric T2 hyperintensity of the right upper trunk (arrow in B). In such cases, the diagnosis is reinforced
by evidence of contrast enhancement in the same region on postcontrast fat-saturated T1-weighted images (arrow in C).

or syrinx. A common artifact, called truncation ­artifact, c­ onfirmed on another imaging plane, usually the
gives the false appearance of subtle linear T2 hyperin- axial plane.
tensities along the spinal cord, mimicking pathology. nn Fat-suppressed T2-weighted images used to assess soft
The technical solution to this artifact is to increase tissues injuries of the spine can suffer from uneven
the frequency matrix of the pulse sequence, usually and inhomogeneous fat suppression, especially in
achieved at no extra scan time cost. Moreover, any patients with metallic instrumentation, thereby fail-
signal abnormality in the spinal cord needs to be ing to completely suppress the high signal from fat
 Chapter 13 Imaging of Spine Trauma 493

SECTION III
A B C

D
Figure 13-23 Multidetector computed tomography (CT) pitfalls in spinal trauma imaging. A: Sagittal reformatted CT view showing L2–L3
dislocation (arrow), but the stepoff of the skin contour line (arrowhead) suggests it might be an artifact caused by minimal patient motion during
the volumetric CT acquisition. This is confirmed by looking at the axial image at the L2–L3 level (B), showing motion (arrowheads), and at the
scout view (C), displaying normal alignment. D: Similar case in which motion during scan acquisition created a fake “bony fracture” (arrows),
which is confirmed by focal discontinuity of the skin contour line (arrowhead).

adjacent to muscles and ligaments. This could be erro- ­ ositioning of hardware implants and to detect signs
p
neously interpreted as soft tissue edema and injury. of instability. Instability can be diagnosed in the pres-
STIR images, although more noisy and of worse qual- ence of abnormal intersegmental motility of the spine
ity than FSE T2-weighted images, guarantee more elements during flexion–extension maneuvers or in the
homogeneous fat signal nulling and are more specific presence of lucent bone resorption around the screws
in identifying soft tissue injuries. Newer fat suppres- of metallic fixation devices. In case of instability, at the
sion techniques, such as two- and three-point Dixon same level, MR STIR images can show high bone mar-
and adiabatic inversion recovery methods, which are row signal as well.
being implemented, will provide superior fat suppres- After a spinal cord injury, the spinal cord abnormal-
sion compared to traditional chemical suppression ity is expected to evolve in the late chronic phase into a
techniques. focal area of myelomalacia, characterized by CSF-like T1
and T2 signal and cord thinning due to atrophic ­volume
What Are the Delayed Findings in loss (Figure 13-24). In this phase following spinal cord
injury, MRI often reveals further hyperintense signal on
Spinal Trauma Imaging?
T2-weighted imaging in the white matter tracts above
After spinal trauma and related interventions, follow- (dorsal columns) and below (lateral columns) the
up imaging is usually performed with plain films radi- injury level. This finding is believed to represent walle-
ography or CT to confirm realignment and correct rian degeneration.
494 Section III  Problem Solving: Disease Categories

A B

C D
Figure 13-24 Spinal cord injury in the chronic phase. A, B: Months after a spinal cord contusion, there is focal thinning and volume loss of
the spinal cord and a central small myelomalacic area in the spinal cord displaying well-defined high T2 cerebrospinal fluid–like signal (arrowhead
in A). C, D: Another case months after a severe cervical spinal cord injury showing diffuse spinal cord volume loss and extensive central high T2,
low T1 signal in the cord. In the absence of cord expansion this more likely is myelomalacia than syrinx.

The neurologic deficit after trauma is supposed of spinal cord injury, including progressive syrinx or
to remain stable; therefore, further MRI follow-up is intramedullary cysts, arachnoiditis with adhesions
needed in the presence of unexpected worsening of and tethering (Figure 13-25), hardware failure, or new
the clinical conditions to rule out the late sequelae compression.
 Chapter 13 Imaging of Spine Trauma 495

Suggested Readings

SECTION III
Anderson LD, D’Alonzo RT. Fractures of the odontoid process of the axis.
J Bone Joint Surg Am.. 1974 Dec;56(8):1663-1674.
Besman A, Kaban J, Jacobs L, Jacobs LM. False-negative plain cervical spine
x-rays in blunt trauma. Am Surg. 2003 Nov;69(11):1010-1014.
Blackmore CC. Evidence-based imaging evaluation of the cervical spine in
trauma. Neuroimaging Clin N Am.. 2003 May;13(2):283-291.
Denis F. Spinal instability as defined by the three-column spine concept in
acute spinal trauma. Clin Orthop Relat Res. 1984 Oct(189):65-76.
Geck MJ, Yoo S, Wang JC. Assessment of cervical ligamentous injury in trauma
patients using MRI. J Spinal Disord. 2001 Oct;14(5):371-377.
Grossman RI, Yousem DM. Non-degenerative diseases of the spine. In:
Grossman RI, Yousem DM, eds. Neuroradiology: the Requisites. 2nd ed.
Philadelphia: Mosby; 2003:837-849.
Hanson JA, Blackmore CC, Mann FA, Wilson AJ. Cervical spine injury: a
clinical decision rule to identify high-risk patients for helical CT screening.
AJR Am J Roentgenol. 2000 Mar;174(3):713-717.
Imhof H, Fuchsjäger M. Traumatic injuries: imaging of spinal injuries. Eur
Radiol. 2002 Jun;12(6):1262-1272.
Mann FA, Cohen WA, Linnau KF, Hallam DK, Blackmore CC. Evidence-based
approach to using CT in spinal trauma. Eur J Radiol. 2003 Oct;48(1):39-48.
A Ross JS, Brant-Zawadzki M, Moore KR, Crim J, Chen MZ, Katzman GL. Trauma.
In: Ross JS, ed. Diagnostic Imaging: Spine. Salt Lake City: Amyrsis; 2004.
Rumboldt Z, Castillo M, Smith K. The spine. In: Lee JKT, Sagel SS, Stanley
RJ, Heiken JP, eds. Computed body tomography with MRI correlation. 4th ed.
Philadelphia: Lippincott Williams & Wilkins; 2006:1669-1683.
Stiell IG, Wells GA, Vandemheen KL, et al. The Canadian C-spine rule
B for radiography in alert and stable trauma patients. JAMA. 2001 Oct
17;286(15):1841-1848.
Takhtani D, Melhem ER. MR imaging in cervical spine trauma. Magn Reson
Imaging Clin N Am. 2000 Aug;8(3):615-634.
Van Geothem JW, Biltjes IG, van den Hauwe L, Parizel PM, De Schepper AM.
Whiplash injuries: is there a role for imaging? Eur J Radiol. 1996
Mar;22(1):30-37.
Van Goethem JW, Maes M, Ozsarlak O, van den Hauwe L, Parizel PM. Imaging
in spinal trauma. Eur Radiol. 2005 Mar;15(3):582-590.
Wilmink JT. MR imaging of the spine: trauma and degenerative disease. Eur
Radiol. 1999;9(7):1259-1266.

C D
Figure 13-25 Posttraumatic arachnoiditis. Several months after
suffering a spinal cord injury, this patient noted new onset of further
progressive neurologic deficit. Magnetic resonance imaging with sagit-
tal T2-weighted (A) and multiplanar reformatted images from a three-
dimensional constructive interference in steady state myelographic
sequence (B–D) showing irregular and multifocal C-spine tethering
with thick irregular septations in the subarachnoid space (arrowheads)
representing arachnoid adhesions. At C2–C3, the site of most severe
cord tethering, there is spinal cord high T2 signal, possibly represent-
ing edema or gliosis (arrow).
 chapter 14

Imaging of Congenital Brain

Abnormalities
Andrea Rossi

INTRODUCTION
rostrum has been ­questioned by Raybaud and Girard,
Brain malformations are extremely polymorphous, and who introduced a new classification of the abnormali-
individual cases very often escape rigid categorization. ties traditionally known as “agenesis and hypoplasia of
Moreover, several malformations are frequently associated the corpus callosum,” a simplified version of which is
with one another in individual patients, and many are presented here. Patients with commissural abnormali-
comprised within complex multiorgan syndromes. Clas- ties are often impaired intellectually and neurologically
sifications schemes are continuously challenged by new (about 90% of cases), a fact that should be considered
advances in the understanding of the pathologies they when such anomalies are discovered antenatally.
attempt to describe. This has especially been the case with
brain malformations. Knowledge of the basic molecular
Commissural Agenesis
and genetic processes that direct normal brain develop-
ment and, when deranged, result in congenital abnor- Commissural agenesis is categorized in three subsets:
malities has literally boomed in the past decade. For this complete commissural agenesis, callosohippocampal
reason, we are now witnessing a delicate transition from agenesis, and isolated callosal agenesis. The most fre-
a purely morphologic to a molecular genetic approach. At quent among the three is callosohippocampal agenesis,
present, both perspectives probably are equally unsatisfac- in which the anterior commissure is preserved. Commis-
tory because the molecular and genetic background is well sural agenesis is characterized by a host of magnetic res-
known for a few entities but is still unavailable for many onance imaging (MRI) features (Figure 14-1), first and
others. Causes of malformations can be divided into four foremost the absent visualization of the corpus callosum
groups: chromosomal abnormalities, single gene muta- in midsagittal scans. Developing axons fail to cross the
tions, environmental agents, and unknown; unfortunately, midline and remain in their native hemisphere, forming
the last category is the largest. Therefore, neuroradiologic the so-called Probst bundles. These run along the medial
classifications are still mostly based on morphology or on walls of the lateral ventricles, characteristically resulting
a combination of morphologic and biochemical data. in crescent-shaped frontal horns in coronal sections.
Because the cingulum (forming the white matter core of
ANOMALIES OF THE CORPUS the cingulate gyrus) is consistently absent, the cingulate
CALLOSUM AND TELENCEPHALIC gyrus does not fold, the callosomarginal sulcus does not
COMMISSURES form, and the mesial cortical sulci show a radial arrange-
ment. Moreover, absence of the cingulum produces thin-
The corpus callosum, hippocampal commissure, and ning of the parahippocampal convolutions, leading to
anterior commissure form the midline telencephalic dilatation of the temporal horns and rudimentary hip-
commissural plate. The corpus callosum is the largest pocampal infolding. Hypoplasia of occipital associative
commissure in the brain. It is anatomically divided in bundles causes colpocephaly, an ex vacuo dilatation of
five portions from anterior to posterior: the rostrum, the trigones of the lateral ventricle. A large amount of
genu, body, isthmus, and splenium. The hippocam- genetic syndromes may be associated with commissural
pal commissure connects the posterior pillars of the abnormalities. Among these, the Aicardi syndrome is
fornix and lies along the inferior aspect of the callosal a dominant X-linked entity characterized by a variable
isthmus and splenium, so the term callosohippocampal association of asymmetric infantile spasms, commis-
commissure has been introduced to illustrate such con- sural agenesis, and chorioretinal lacunae, found in infant
tinuity. The anterior commissure crosses the midline girls. Choroid plexus papillomas may also be associated.
at the superior end of the lamina terminalis. Embryo-
logically, the telencephalic commissures derive from Commissural Hypoplasia
the lamina reuniens, a dorsal thickening of the embry-
onic lamina terminalis. The concept that callosal devel- Commissural hypoplasia is divided into three categories:
opment starts from the posterior portion of the genu partial posterior commissural agenesis, diffuse commis-
and proceeds bidirectionally toward the splenium and sural hypoplasia, and segmental callosal ­hypoplasia.

496
 Chapter 14 Imaging of Congenital Brain Abnormalities 497

SECTION III
A B
Figure 14-1 Callosohippocampal agenesis in a 7-year-old girl. A: Sagittal T1-weighted image showing complete absence of the corpus cal-
losum and the hippocampal commissure. The anterior commissure is present (arrow). The roof of the third ventricle bulges upward slightly. The
normal appearance of the cingulate gyrus is not found. B: Coronal T2-weighted image confirming no interhemispheric commissure. The medial
cortex is rolled-in over the thalami. The lateral ventricles are away from each other, closed medially by the primordial septal leaves that contain the
longitudinal bundles of Probst (arrow). The temporal horns have an abnormal appearance, extending below the hippocampus into the parahip-
pocampal gyrus (arrowhead), presumably because of the lack of cingulum. This lack of cingulum could also explain the loss of the normal pattern
of the cingulate gyrus.

Partial posterior commissural agenesis is characterized HOLOPROSENCEPHALIES

by partial agenesis of the posterior portion of the cor-
AND RELATED ENTITIES
pus callosum. The extent of the agenetic portion may
be variable, with only part of the genu (corresponding Holoprosencephaly
to the portion of the corpus callosum that forms first)
present in the most severe cases. It is predictable based Holoprosencephaly (HPE) is a complex developmental
on the traditional theory of bidirectional development anomaly of the brain and skull, characterized by hypopla-
of the corpus callosum. Diffuse commissural hypoplasia, sia of the most rostral portions of the neural tube result-
characterized by diffuse thinning of the three commis- ing in noncleaved cerebral hemispheres and absence of
sures, could be related to errors occurring later during midline structures such as the rhinencephalon, corpus
commissural plate development, resulting in a lesser callosum, and septum pellucidum. Both genetic factors
amount of fibers crossing the commissures. Segmental (either chromosomal aberrations or single-gene muta-
callosal hypoplasia, in which an intermediate portion of tions) and extrinsic teratogens (including maternal dia-
the corpus callosum is thinned, must be differentiated betes mellitus) may be involved in the pathogenesis.
from secondary callosal destruction. Currently, nine human HPE genes are known, and more
likely will be discovered in the future; therefore, it prob-
Associated Findings ably is incorrect to think of a gene “for” HPE. Rather, it
is the action of a gene(s) with the environment of the
Interhemispheric Cysts developing embryo that determines the outcome. HPE
Cerebrospinal fluid (CSF)–filled cavities associated is classically divided into alobar, semilobar, and lobar
with commissural abnormalities belong to two main types according to the severity of the malformation.
categories: diencephalic pseudocysts, representing supe- However, a precise boundary among the three groups
rior bulging of the tela choroidea of the third ventri- does not exist, and intermediate cases may be identified.
cle, and interhemispheric cysts (Figure 14-2, A), which
are independent from the ventricles and may in turn Alobar HPE
be intraparenchymal, subarachnoid, arachnoid, or Midline structures such as the falx cerebri, superior sag-
even intradural. True interhemispheric cysts suggest ittal sinus, interhemispheric fissure, septum pellucidum,
that commissural development may influence, and corpus callosum, third ventricle, pituitary gland, and
in turn be influenced by, development of the meninx olfactory bulbs are absent. The thalami are fused and
primitiva. abut a rudimentary ventricle that freely communicates
with a large cyst, the dorsal sac, that extends upward to
Lipomas the calvarium. Facial abnormalities ranging from cyclo-
The deep interhemispheric fissure is a common location pia to ethmocephaly are commonly associated. The
for intracranial lipomas (so-called lipomas of the corpus diagnosis usually is made antenatally by ultrasound.
callosum). Commissural plate abnormalities are almost Neonates usually are stillborn and therefore are rarely
invariably associated (Figure 14-2, B). imaged by MRI.
498 Section III  Problem Solving: Disease Categories

B
Figure 14-2 Callosohippocampal agenesis and associated anomalies. A: Axial T2-weighted image of a 2-month-old girl showing multiple
interhemispheric cavities. The right lateral ventricle is enlarged, whereas the left lateral ventricle is difficult to identify. The cortex of the medial
aspect of the left cerebral hemisphere is dysplastic, with subcortical heterotopia. B: Sagittal T1-weighted image of a 3-year-old boy showing tubu-
lonodular lipoma overlying a dysplastic corpus callosum. (From Tortori-Donati P, Rossi A, Biancheri R. Brain malformations. In: Tortori-Donati
P (ed) Pediatric Neuroradiology. Berlin: Springer, 2005:71-198.).
 Chapter 14 Imaging of Congenital Brain Abnormalities 499

Semilobar HPE Lobar HPE

SECTION III
The brain is less dysmorphic. Rudimentary lateral ven- Lobar HPE is the mildest form, usually found in asymp-
tricles are present, and the cortex is more developed. tomatic or mildly retarded individuals. The lateral ven-
The thalami may be partially separated, and a rudimen- tricles are formed. The frontal lobes may be partially
tary third ventricle may be seen. The interhemispheric fused in some cases and separated in others, but the sep-
fissure and the falx cerebri are partially developed pos- tum pellucidum is constantly absent. The mildest forms
teriorly, whereas the frontal lobes and basal ganglia show only the absence of the septum pellucidum and
are not separated (Figure 14-3). The corpus callosum therefore require differentiation from septooptic dyspla-
is absent in the fused regions, whereas a commissure sia, in which optic nerves are hypoplastic. The differen-
(“pseudosplenium”) is visible where the two cerebral tiation from the semilobar variant is sometimes difficult
hemispheres are separated. Affected patients are usually by MRI due to the large amount of intermediate forms.
afflicted by severe psychomotor delay. The degree of anterior extension of the corpus callosum
in midsagittal planes may be used as a gross indicator of
the severity of the malformation.

Syntelencephaly (Middle Interhemispheric HPE)

This rare abnormality is characterized by failure of cleav-
age of the posterior frontal and parietal regions of the
brain despite separation of the rostrobasal forebrain,
with presence of an interhemispheric fissure anteri-
orly (Figure 14-4). The nervous tissue that bridges the
midline may be represented by a heterotopic nodule or
cortical dysplasia. Patients are usually severely retarded
developmentally, although normal intelligence was
reported in one case.

Septooptic Dysplasia
It is characterized by the association of hypoplastic
optic nerves and absent septum pellucidum. The clini-
cal presentation is related to the association with either
schizencephaly (presenting with seizures) or hypo-
thalamic and pituitary hypoplasia (presenting with
Figure 14-3 Semilobar holoprosencephaly in a 5-month-old girl. pituitary insufficiency). The diagnosis of septooptic
Axial T2-weighted image showing incomplete cleavage of the fron- dysplasia is based on ophthalmoscopy, which shows
tal lobes and basal ganglia (arrows). The interhemispheric fissure is hypoplastic optic discs, and a MRI picture of small
formed posteriorly (arrowheads), consistent with normal cleavage of
the posterior region of the brain. Correspondingly, the trigones of the optic nerves and chiasm and absent septum pellu-
lateral ventricles, albeit rudimentary, are formed, whereas the frontal cidum. The association with schizencephaly (“septo-
horns show agenesis. optic dysplasia plus”) must be accurately scrutinized.

A B
Figure 14-4 Syntelencephaly in a mildly hypotonic 14-year-old boy with normal intelligence. A: Axial T2-weighted image showing rudimen-
tary lateral ventricles but septum pellucidum is absent; however, normally developed interhemispheric fissure both anteriorly and posteriorly
(arrows) does not suggest holoprosencephaly at first glance. B: Sagittal T1-weighted image showing partial intermediate dysgenesis of the corpus
callosum. A thin cortical bridge (arrows) overlies the markedly thinned callosal body. G, Genu; S, splenium. (From Tortori-Donati P, Rossi A,
Biancheri R. Brain malformations. In: Tortori-Donati P (ed) Pediatric Neuroradiology. Berlin: Springer, 2005:71-198.)
500 Section III  Problem Solving: Disease Categories

The frontal horns show a square-like shape due to the f­ requently dilated, and the frontal horn is stretched. The
absence of the septum pellucidum, a feature in com- ­homolateral cerebellar hemisphere is usually enlarged
mon with lobar HPE. as well. Affected newborns suffer from untreatable epi-
lepsy, so hemispherectomy is often necessary. However,
MALFORMATIONS OF THE CEREBRAL because hemispherectomy is contraindicated if the
contralateral hemisphere has cortical malformations,
CORTEX
assessment of the contralateral hemisphere is crucial.
Embryology and Classification
Focal Cortical Dysplasia
The complex events leading to the formation of the
cerebral cortex may be simplified in three main steps: Focal cortical dysplasia (FCD) affects children with
proliferation, migration, and organization. Proliferation partial, intractable epilepsy. It presently is categorized
begins during the seventh gestational week, when cells into three grades. Grade I (or architectural) and grade
in the subependymal layer of the walls of the lateral ven- II (or cytoarchitectural) are often found in association
tricles form the germinal matrix. During the following with hippocampal sclerosis (dual pathology). They are
week, neurons generated by intense mitotic activity in characterized by a hypoplastic appearance of one tem-
the germinal matrix begin to migrate radially toward the poral lobe with loss of gray–white matter demarcation.
surface of the brain; such migration follows a track laid Grade III FCD corresponds to the so-called Taylor-type
by specialized radial glial fibers. When migration in the FCD, which in turn is categorized into two subgroups
cortex of the human fetus stops is not clear. However, based on the presence or absence of balloon cells (i.e.,
distal processes of the radial glia disappear by 20 to 28 large cells with abundant eosinophilic cytoplasm,
weeks of gestation, suggesting no or little migration on showing intermediate features between neuronal and
glial guides at this stage. Organization of the cortex to glial elements). Such classification is valuable because
the eventual six-layer configuration occurs next and is it correlates with epilepsy surgery outcome. In fact, an
completed by the seventh lunar month. The current inverse correlation between histologic grade and per-
classification categorizes cortical malformations into centage of seizure-free patients after 1 year of follow-
defects of proliferation, migration, and organization. up has been found. Patients usually suffer from partial
Only the main entities are described here. intractable epilepsy. Because the histologic abnormal-
ity, which is reflected in corresponding MRI features
Hemimegalencephaly (see below), involves not only the cortex but the whole
thickness of the cerebral mantle (i.e., from the ventric-
Hemimegalencephaly results from a disorder in neu- ular to the pial surface), Taylor-type FCD has also been
ronal and glial proliferation in the germinal matrix. It called focal transmantle dysplasia. On MRI, Taylor-type
may be isolated or occur in patients with neurocuta- FCD shows a triad of focal cortical thickening with
neous syndromes. MRI shows enlargement of a whole enlargement of the affected gyri, blurred gray–white
hemisphere (Figure 14-5). The cortex is affected by dif- matter interface, and a funnel-shaped high T2/fluid-
fuse migration anomalies, whereas the white matter is attenuated inversion recovery signal intensity in the
gliotic and dysmyelinated. The ipsilateral ventricle is subcortical white matter that tapers toward the lateral
ventricle (Figure 14-6).

The Lissencephaly Spectrum

The term lissencephaly refers to a complete lack of sulca-
tion of the cortical plate and therefore should be con-
sidered synonymous with agyria, whereas pachygyria
indicates few, broad gyri with shallow sulci. However,
there is a wide spectrum of intermediate features in
which variably combined areas of agyria and pachy-
gyria coexist. Several forms of lissencephaly have been
­identified, the most relevant of which are briefly dis-
cussed here.
Classical lissencephaly can be caused by abnormali-
ties of either the LIS1 gene on chromosome 17 or the
DCX gene on chromosome X (i.e., X-linked lissen-
cephaly). Patients are usually severely affected with
intractable epilepsy and profound psychomotor delay.
Histologically, there is a four-layered cortex with a
thick sparse cell layer interposed between the exter-
Figure 14-5 Hemimegalencephaly in a newborn. Axial T2-weighted nal and internal cellular layers. On MRI (Figure 14-7),
image showing general increase in size of right cerebral hemisphere
with cortical thickening. Relative hypointensity of the frontal white
the cortical surface is flat and the sylvian cisterns are
matter is consistent with hypermyelination. Notice marked dilatation broad and vertically oriented; therefore, the brain has
of the lateral ventricle. a figure-of-eight shape in axial sections. The cortex is
 Chapter 14 Imaging of Congenital Brain Abnormalities 501

SECTION III
A B
Figure 14-6 Taylor-type focal cortical dysplasia in a 5-year-old boy. On magnetic resonance imaging, Taylor-type focal cortical dysplasia shows
a triad of focal cortical thickening with enlargement of the affected gyri, blurred gray–white matter interface, and funnel-shaped high T2/fluid-
attenuated inversion recovery (FLAIR) signal intensity in the subcortical white matter that tapers toward the lateral ventricle. A: Coronal inversion
recovery image showing focal cortical thickening in the right frontal lobe (arrows). B: Axial FLAIR image showing hyperintensity that tapers toward
the lateral ventricle (arrowheads).

Figure 14-7 Classic lissencephaly in a 3-month-old boy. Axial

T2-weighted image showing the brain has a figure-of-eight appearance
due to shallow, vertically oriented sylvian fissures. The brain surface is
entirely smooth. Thickness of the cortical plate is much greater than Figure 14-8 Subcortical band heterotopia in a 13-year-old girl.
that of white matter. The sparse cells layer, separating the thin outer Axial inversion recovery image showing thick layer of heterotopic neu-
cortical layer from the thick layer of arrested neurons, is clearly recog- rons (arrowheads) located deep to a grossly normal-appearing cortex
nizable as a hyperintense stripe (arrowheads). and extending continuously along both hemispheres bilaterally. The
band is separated from the cortex by a layer of myelinated white mat-
ter. Note that the convolutions are somewhat coarse, and the gyral
pattern probably is simplified.
thickened, and the ­hyperintense sparse cells layer is
usually visualized. A variable degree of sulcation can
be present in individual patients. LIS1 gene mutation Cobblestone lissencephaly is usually found in chil-
is characterized by a ­combination of posterior agyria dren with Fukuyama congenital muscular dystrophy,
and anterior pachygyria, whereas the opposite pattern ­Walker-Warburg syndrome, and muscle-eye-brain dis-
(i.e., anterior agyria and posterior pachygyria) is found ease. There is a more anarchic disorganization of the
in DCX mutations. cortex, with zones of typical lissencephaly interspersed
Subcortical band heterotopia is found in female carri- among areas of polymicrogyria. Cortical lamination is
ers of the DCX mutation. In this entity, the majority of absent, and subcortical heterotopia may be found. On
radial glial fibers are damaged, manifesting with bilat- MRI (Figure 14-9), the cortex is thinner than in classic
eral, thick layers of arrested neurons located approxi- lissencephaly, and there may be concurrent hypomy-
mately halfway between the ventricles and the cortical elination of the white matter. Brainstem hypoplasia and
plate, resembling a doubling of the cortex (Figure 14-8). cerebellar malformations are commonly associated.
502 Section III  Problem Solving: Disease Categories

A B
Figure 14-9 Cobblestone lissencephaly in a 3-year-old girl with muscle-eye-brain disease. A: Axial inversion recovery image showing thickened
cortical ribbon with coarse gyration involving both frontal lobes (arrowheads). B: Sagittal T1-weighted image showing hypoplasia of the pons
(arrow) and inferior vermis (arrowheads).

Figure 14-10 X-linked bilateral periventricular nodular heteroto- Figure 14-11 Polymicrogyria in a 2-year-old girl with congenital
pia in a 16-year-old girl who had her first seizure at age 14 years. Axial left hemiplegia. Axial T2-weighted image showing the right cerebral
fluid-attenuated inversion recovery image showing bilateral subep- hemisphere is smaller than the left and the cortical mantle is appar-
endymal nodules that are isointense with gray matter (arrowheads). ently thickened, resulting from fusion of multiple adjacent small gyri.
(Courtesy Dr R. Guerrini, Florence, Italy.) The cortical surface is flattened.

Polymicrogyria
Subependymal Heterotopia
Polymicrogyria is the most frequent cause of partial
Damage of radial glial fibers may arrest neuronal migra- epilepsy in pediatric patients, although unilateral poly-
tion at anomalous sites, where neurons conglomerate in microgyria may present with congenital hemiparesis.
a disorganized fashion. Patients almost always present Either genetic or acquired factors, including vascular
with a seizure disorder. Gray matter heterotopia may be events or congenital infection, can be implicated in
subependymal, subcortical, or meningeal. Among these, the pathogenesis. Polymicrogyria may be unilateral
subependymal heterotopia is by far more common. The or bilateral, resulting in various appearances depend-
heterotopic nodules are isointense with normal gray ing on the extent of hemispheric involvement. Macro-
matter in all MRI sequences. Focal nodules are found in scopically, there is excessive infolding of the cortex with
sporadic cases. Diffuse heterotopia bordering the walls thin, numerous microconvolutions separated by nar-
of the lateral ventricles is more likely to be X-linked due row and often obliterated sulci. On MRI (Figure 14-11),
to defects of the FLN1 gene (Figure 14-10). ­polymicrogyria appears as an area of increased ­cortical
 Chapter 14 Imaging of Congenital Brain Abnormalities 503

SECTION III
Figure 14-12 Schizencephaly in a 3-year-old girl. Axial T2-weighted Figure 14-13 Dandy-Walker malformation in a 20-month-old girl.
image showing deep fissure involving the entire thickness of the right The posterior fossa is enlarged and filled with a huge cerebrospinal
cerebral hemisphere. The deep portion of the cleft is fused, with a dimple fluid cavity, corresponding to an enlarged fourth ventricle. The vermis
along the ventricular wall (black arrow). Polymicrogyric cortex surrounds is hypoplastic with verticalization (i.e., counterclockwise rotation of
both lips of the fissure (arrowheads). Polymicrogyria also involves the con- the vermis) (arrow) and elevated tentorial insertion/torcula. Associ-
tralateral hemisphere, with deep infolding (white arrow). Large drainage ated hydrocephalus is evident.
veins into the dilated cerebrospinal fluid spaces are visible on both sides.

other until they eventually fuse in the midline to form

thickness with an irregular gray–white matter junc- the vermis. The intervening AMA progressively invo-
tion, whereas the cortical surface may be flat or extend lutes until its remnants are incorporated in the choroid
inward, producing a cortical infolding around an abnor- plexus. Meanwhile, the PMA shows a transient posterior
mally oriented sulcus. Anomalous venous drainage is finger-like expansion, the Blake pouch, which disappears
common in dysplastic cortical areas, and large veins as the foramen of Magendie opens. Cerebellar malfor-
may often be seen within the abnormal sulci. mations derive from an imbalance between the forma-
tion of the rhombic lips and of the choroid plexuses on
Schizencephaly one side and the involution of the AMA and PMA on
the other side. A further categorization individuates cys-
Schizencephaly is characterized by a cleft extending tic malformations, in which a collection resulting from
through the whole hemisphere, from the ependymal active expansion of CSF spaces is found within the pos-
lining of the lateral ventricle to the pia covering the terior cranial fossa, and noncystic malformations, which
brain. The cleft may be unilateral or bilateral and is con- are usually dominated by vermian dysgenesis.
stantly lined by polymicrogyric cortex. The walls of the
cleft may be widely separated by intervening CSF (open Dandy-Walker Malformation
lips) or abut one another (closed lips). In the latter case,
the cleft may not be easily visible, although a dimple The definition of Dandy-Walker malformation clas-
may be seen in the wall of the lateral ventricle where the sically includes partial or complete vermian agenesis
cleft communicates (Figure 14-12). Presence of dysplas- associated with hypoplastic cerebellar hemispheres,
tic cortex lining the cleft is of primary importance to dif- ­cystic dilatation of the fourth ventricle, and expansion
ferentiate schizencephaly from porencephalic cavities. of the posterior fossa associated with high insertion
of the tentorium, torcular Herophili, and transverse
MALFORMATIONS OF THE sinuses (Figure 14-13). Vermian hypoplasia may be
more or less severe; however, the hypoplastic superior
CEREBELLUM
vermis is ­constantly rotated in a counterclockwise fash-
Embryology ion and often lies posterior to the quadrigeminal plate.
Cerebellar hemispheres are also hypoplastic and abut
By gestational day 28 to 37, the thin roof of the rhomb- the petrous ridges. The posterior fossa is occupied by a
encephalon (future fourth ventricle) is formed by an large cyst that corresponds to a dilated fourth ventricle.
ependymal membrane coated by pia mater. The plica Hydrocephalus develops in up to 80% of untreated cases.
choroidea, a precursor of the future choroid plexus, In some cases, key features of Dandy-Walker malforma-
divides the rhombencephalic roof into the anterior mem- tion (e.g., rotated, hypoplastic vermis and cystic dilata-
branous area (AMA) lying cephalad and the posterior mem- tion of the fourth ventricle) may be found in patients
branous area (PMA) lying caudad. The edges of the AMA with a normal-sized posterior fossa. The term Dandy-
thicken progressively by cellular proliferation, forming Walker variant was used to describe these minor forms.
the rhombic lips. These paired structures approach each However, there presently is no consensus regarding the
504 Section III  Problem Solving: Disease Categories

Figure 14-15 Persistent Blake pouch in a 6-month-old boy. Sag-

ittal T2-weighted image showing tetraventricular hydrocephalus.
The fourth ventricle is markedly enlarged and communicates with a
Figure 14-14 Mega cisterna magna in a 2-month-old boy. Sagittal large infravermian cystic formation representing persistence of the
T2-weighted image showing the subarachnoid spaces of the posterior Blake pouch (BP). The cerebellar vermis is normally formed and not
fossa are enlarged, with scalloping of the occipital squama (arrow- rotated, although its inferior surface is compressed. Posterior fossa
heads). Note there is no hydrocephalus. Both the vermis and brainstem size is normal.
are normally formed. Posteriorly, the mega cisterna magna insinuates
itself into a small fenestration of the tentorial insertion (arrow).
­ alformation typically is found in patients with Jou-
m
exact significance of this term. Probably, Dandy-Walker bert syndrome, who present clinically in the neonatal
malformation and Dandy-Walker variant represent two age with hyperpneic–apneic spells, ataxia, nystagmus,
ends of the spectrum of AMA anomalies, with the main and developmental delay. Other entities in the so-called
difference being the degree of dilatation of the fourth cerebello-oculo-renal syndrome spectrum (including Arima,
ventricle and, therefore, of the posterior fossa. Senior-Loken, and Coach syndromes) may display a
similar malformation. On MRI (Figure 14-16), the ver-
Mega Cisterna Magna mis is completely or partially absent, with only the ante-
rior lobules visible. The fourth ventricle is high riding
This abnormality is characterized by dilatation of the with an umbrella shape on axial images. The superior
cisterna magna with free communication with both the cerebellar peduncles are elongated, thickened, and proj-
fourth ventricle and the adjacent subarachnoid spaces ect straight back, running parallel with each other.
(Figure 14-14). The vermis, cerebellar hemispheres, and
fourth ventricle are normal. Hydrocephalus is never CHIARI MALFORMATIONS
associated, and the anomaly is constantly clinically
silent but usually is encountered during MRI for other Chiari I
indications.
Chiari I malformation is characterized by bilateral or,
Persistent Blake Pouch less frequently, unilateral ectopia of the cerebellar ton-
sils into the foramen magnum by greater than 5 mm
Persistent Blake pouch is characterized by a retro- (Figure 14-17). The posterior fossa is usually normal
cerebellar CSF collection that, in itself, is similar to a or slightly smaller than normal, and the vermis is nor-
mega cisterna magna. However, persistence of the Blake mally shaped and located. Associated hydrocephalus
pouch is characterized by failed permeabilization of the and hydromyelia are frequent and may be secondary to
Magendie foramen, resulting in tetraventricular hydro- restricted CSF flow at level of the crowded foramen mag-
cephalus (Figure 14-15). Shunting of the retrocerebel- num. In rare cases, the medulla oblongata is elongated
lar pouch restores normal CSF outflow so that both the sagittally and shows a prominent obex (myelencephalic
hydrocephalus and the pouch are resolved. variant). Affected patients may be asymptomatic or may
complain of headache, torticollis, cervical pain, and cra-
Molar Tooth Malformation nial nerve palsies. Cine MRI studies of CSF flow are use-
ful for selecting candidates for decompression surgery
Molar tooth malformation consists of the following and for evaluating the results.
triad: (1) dysgenesis of the isthmic portion of the brain-
stem with elongation and thinning of the pontomesen-
Chiari II
cephalic junction and elongation of the interpeduncular
fossa; (2) thickened superior cerebellar peduncles that There is a consistent association between myelome-
project straight back, coursing perpendicular to the ningoceles and Chiari II malformation, a complex
brainstem; and (3) hypoplasia of the vermis. This congenital anomaly of the hindbrain characterized
 Chapter 14 Imaging of Congenital Brain Abnormalities 505

SECTION III
A B
Figure 14-16 Molar tooth malformation in a 4-year-old girl. A: Axial T2-weighted image showing thickening of the superior cerebellar pedun-
cles (arrows) resulting in a molar tooth appearance of the midbrain. Note abnormal foliation of the superior vermis. B: Sagittal T1-weighted image
showing marked hypoplasia of the cerebellar vermis (V). The hemispheres (H) abut one another on the midline.

Figure 14-17 Chiari I malformation in a 6-year-old boy. Sagittal Figure 14-18 Chiari II malformation following ventriculoperi-
T1-weighted image showing the cerebellar tonsils (T) herniating into toneal shunting in a 2-year-old boy who had previously undergone
the foramen magnum by more than 5 mm (arrow). Note that the ver- myelomeningocele surgery. The posterior fossa is markedly small
mis (V) is not herniated; instead, it is raised by the underlying tonsils. and crowded. The vermis herniates through the foramen magnum
(arrows), whereas the cerebellum engulfs the brainstem (arrowheads).
The fourth ventricle is effaced. Additional signs include crowding of
the occipital convolutions (i.e., stenogyria), an “accessory lobe” (aster-
by caudal displacement of the vermis, brainstem, and isk) due to medialization of the posterior temporal lobe, and a thick-
fourth ventricle. However, the severity of the hindbrain ened interthalamic mass (IM).
malformation may be variable, so patients with a nearly
normal-sized posterior fossa may sometimes be found.
Therefore, subtle minimal features of Chiari II malfor- (Figure 14-18) and consequently herniate through both
mation should be actively sought in all newborns with the tentorial groove and the foramen magnum. The
open spinal dysraphisms. CSF leaks through the spinal inferior vermis herniates into the foramen magnum and
defect into the amniotic sac result in chronic CSF hypo- wraps around the posterior surface of the cord (cerebel-
tension within the developing neural tube, insufficient lar peg). The medulla is stretched downward into the
dilatation of the rhombencephalic vesicle (future fourth foramen magnum while the cervical cord is anchored
ventricle), and lack of induction of the perineural mes- by the dentate ligaments, resulting in the cervicomedul-
enchyma of the posterior cranial fossa. Therefore, both lary kink, best seen on sagittal views. Hydrocephalus is a
the cerebellum and the brainstem are eventually forced consistent finding in newborns within 48 to 72 hours of
to develop within a smaller than normal posterior fossa repair of the spinal dysraphism.
506 Section III  Problem Solving: Disease Categories

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 chapter 15

Epilepsy
Pascal Bou-Haidar, Saulo Lacerda, and Meng Law

INTRODUCTION
New-onset seizures:
Seizures are caused by abnormal and excessive dis- nn Routine brain with contrast
charges from the cortical neurons. Epilepsy is a general nn Axial gradient-recalled echo (GRE) T2*
term used for a group of chronic neurologic disorders nn Diffusion weighted images
manifesting as spontaneous, recurrent seizures. The Recurrent seizures:
mean prevalence of epilepsy is estimated at 0.52% in nn Noncontrast MRI study
Europe, 0.68% in the United States, and peaks up to nn Coronal T2, fluid-attenuated inversion recovery
1.5% in developing countries. (FLAIR)
The epilepsies are broadly classified into generalized nn Coronal three-dimensional (3D) volume T1
and focal groups. Partial or focal seizures start from a (1.5 mm) whole-brain GRE
localized unilateral area of the cerebrum versus simulta- Seizure protocol (Figure 15-1, A and B):
neously from both hemispheres in generalized seizures. nn Magnetization-prepared rapid acquisition of gradi-
In one fourth of patients who suffer from partial sei- ent echo (MPRAGE), whole-brain sagittal T1
zures, the condition is not adequately controlled with nn Coronal, axial T1
anticonvulsive medication. This is the group of patients nn Coronal T2 (512 × 512 matrix)
who are potential candidates and could profit from sur- nn Coronal FLAIR
gical epilepsy treatment. The success rate for such surgery nn Axial GRE
is greatest when a structural lesion related to the epi- nn Diffusion MRI
lepsy can be identified. This lesion usually points to the nn Postcontrast axial T1
epileptogenic zone. Resection of the epileptogenic zone nn 1H Magnetic resonance spectroscopy and dynamic
is needed to stop the recurrence of seizures. Hence the susceptibility contrast MRI
primary goal of imaging epilepsy patients is detecting The standard imaging protocol for evaluation of epi-
these lesions and determining their spatial relationship lepsy at the Mount Sinai Medical Centre is given in Table
to eloquent cortical areas. Table 15-1 lists definitions of 15-2.
the zones and lesions of the cortex. Excellent alignment is particularly important for evalu-
ating the hippocampus. The hippocampus is best visual-
ROLE OF MAGNETIC RESONANCE ized along its long axis (~35% to the orbitomeatal line)
and orthogonal to this line. The axial plane, which is along
IMAGING IN EPILEPSY WORKUP
the line joining the base of the splenium of the corpus cal-
Magnetic resonance imaging (MRI) plays a central role losum to the inferoposterior border of the frontal lobe, is
in the evaluation of patients with epilepsy. Computed determined on a sagittal scout image (Figure 15-2).
tomographic (CT) imaging still is useful in emergency
settings for screening patients with new onset of seizure LOCATIONS FOR TYPES OF CLINICAL
and for ruling out surgical emergencies such as acute PRESENTATION: CLUES TO LOCATION
intracranial hemorrhage.
MRI is a versatile diagnostic tool in the evaluation of The clinical symptoms and particular auras in par-
patients with epilepsy due to its inherent excellent soft tial seizure often serve as useful clues to possible focal
tissue contrast and high spatial resolution. MRI proto- regions of the brain from which seizures are generated
cols should be optimized and selected based on their (Table 15-3).
ability to assess epileptogenic lesions such as cortical
dysplasia, gray matter heterotopia, and hippocampal Limbic System Anatomy
sclerosis. In 60% of patients with partial seizures and
focal brain lesions, the lesion is located in the temporal The noncortical areas that are part of the limbic system
or frontal lobe. include the following (Figure 15-3):
nn Amygdala
nn Septal nuclei
MRI PROTOCOL nn Basal ganglia
The core imaging protocol is different for new-onset nn Thalamus
­versus recurrent seizures. nn Hypothalamus

507
508 Section III  Problem Solving: Disease Categories

Table 15-1 Zones and Lesions of the Cortex nnLimbic midbrain

nnOlfactory system
Epileptogenic zone Region of cortex indispensible
for generation of seizures
Extensive texts discuss the limbic system in detail; how-
By definition, total removal is ever, for our purpose, one important circuit (of Papez)
necessary and sufficient for seizure and hippocampal formation are briefly discussed here
freedom because they are important for understanding changes
Irritative zone Region of cortex that generates in temporal lobe epilepsy.
interictal epileptiform discharges on
EEG or MEG Papez Circuit
Seizure-onset zone Region of cortex where the clinical In 1937, Papez postulated a classic neuronal circuit rep-
seizure originates resenting one of the anatomic substrates of memory and
emotion. It is important for understanding the patho-
Epileptogenic lesion Structural lesion that is causally
related to the epilepsy logic findings in mesial temporal sclerosis (MTS), dis-
cussed later. The Papez circuit starts in the cingulated
Ictal symptomatogenic Region of cortex that generates the cortex, which projects to the parahippocampal gyrus via
zone initial seizure symptoms
the cingulated bundle and then to the hippocampus via
Functional deficit Region of cortex that in the interictal the entorhinal cortex. The fornix connects the hippo-
period is functionally abnormal as campus with the mamillary body and via the mammil-
indicated by neurologic examina-
tion, neuropsychological testing, and lothalamic tract project to the anterior thalamic nucleus.
functional imaging or nonepilepti- The thalamocingulate fibers complete the Papez circuit
form EEG or MEG abnormalities by connecting back to the cingulated gyrus. More recent
Eloquent cortex Region of cortex that is indispen- work has expanded the circuitry to encompass the
sible for defined cortical functions remainder of the complex limbic system and includes
structures such as the amygdala, prefrontal cortex, and
EEG, Electroencephalography; MEG, magnetoencephalography. other parts of the hypothalamus.

A B C

D E F
Figure 15-1 Magnetic resonance imaging protocol, sample sequences. A: Sagittal T1-weighted imaging B: Axial diffusion-weighted imaging
and apparent diffusion coefficient. C: Axial T2-weighted imaging. D: Coronal T1-weighted imaging. E: Coronal fluid-attenuated inversion recov-
ery. F: Coronal T2-weighted imaging.
 Chapter 15 Epilepsy 509

SECTION III
Seizure

No
First Epilepsy

Yes

Child Adult

Yes Focal motor

Febrile Acute
or meningeal symptoms
signs or neuro-
signs
No No
Yes
No Yes

Neuroimaging: Neuroimaging: Neuroimaging Neuroimaging: – Neuroimaging:

(CT) (CT) not recommended MRI (CT)

– Old Acute + + – +
lesions lesions*

First First Acute Febrile seizures Remote First Acute

unprovoked unprovoked symptomatic (6 months–5 years) symptomatic unprovoked symptomatic
cryptogenic remote seizure seizure cryptogenic seizure
seizure symptomatic seizure
seizure
Complex Simple

Anoxic-ischemic Meningitis First episode Low Gliosis CVA

injury Encephalitis Higher risk of epileptogenic HS Trauma
SNC-tumor Abscess recurrence threshold Neoplasia Infections
Brain dysgenesis CVA (Benign?) Degenerative Toxic-metab
Cysticercosis Neoplasia?
Other Trauma
Tumor
CVA
Hemmorhage
G
Figure 15-1, cont’d G: New-onset seizure flowchart. CVA, Cerebrovascular accident; HS, hippocampal sclerosis.
510 Section III  Problem Solving: Disease Categories

Table 15-2 Standard Imaging Protocol for Evaluation of Epilepsy at the Mount Sinai Medical Centre
Coronal Coronal
Sagittal Axial Oblique 3D Oblique XETA 3D Axial T2
Sequence T1 FLAIR T2 ­Propeller SPGR T2 FLAIR SWAN* Axial DWI FLAIR
FOV 220 210 210 240 240 240 220
Matrix 288 × 192 320× 256 512× 192 256× 256 320× 96× 128 288× 256
192
Scan (%) 100 100 100 90 80 100 100
TI 785 — — — — — —
TR 1839 4800 6250 MIN 7625 9500
TE 24 91.2 MIN MIN 55 MIN 135.1
FA 35 30
Slice thickness 5 5 2.5 2.0 3.0 5.0 5.0
(mm)
Interslice gap 2.5 0 0 0 0 0 0
(mm)
No. of slices 17 30 32 60 50 30 30
NSA 2 1.5 1 1 1 1 1
Acquisition 1:35 2:30 1:10 3:48 4:03 1:09 2:51
time/min
*An alternative sequence to 3D SWAN is a coronal gradient-recalled echo sequence.
3D, Three-dimensional; DWI, diffusion-weighted imaging; FA, flip angle; FLAIR, fluid-attenuated inversion recovery; FOV, field of view; NSA, number of signal
­averages; SPGR, spoiled gradient-recalled; SWAN, T2 star-weighted angiography; XETA, extended echo-train acquisition.

Temporal Lobe Anatomy

The fusiform gyrus is also known as the occipitotemporal
gyrus. It lies lateral to the collateral sulcus and is sepa-
rated from the interior temporal gyrus by the occipito-
temporal sulcus.

Internal Architecture
of the Hippocampus
The hippocampal formation includes older cortical
regions, all consisting of fewer than six layers deep in the
most medial aspect of the temporal lobe (Figure 15-4).
The term includes the following:
nn Hippocampus proper or cornus ammonis (CA),
which is divided into four regions (CA1 to CA4) and
has a three-layered cortical area
nn Dentate gyrus, which also has three layers
nn Subiculum, a transitional cortical area of three to five
layers that becomes continuous with the parahippo-
campal gyrus and is the origin of the majority of for- Figure 15-2 Magnetic resonance imaging technique used to plan
coronal sections perpendicular to the long axis of the hippocampus
niceal fibers (red lines).

COMMON EPILEPTOGENIC LESIONS

may have a remote history of a cortical insult, such as
head trauma, complicated febrile seizures, or infection
Mesial Temporal Sclerosis
in the first decade of life. Histologic findings include
The most common candidates for surgical treatment of hippocampal atrophy with neuronal loss in the dentate,
epilepsy are patients with intractable temporal lobe epi- CA1 (Sommer sector), and CA3/CA4 regions with glio-
lepsy. MST is one of the most common causes of epilepsy sis (Figure 15-5). Given the connections to other neuro-
in the adolescent and young adult populations, and sur- nal structures via the Papez circuit, it is not uncommon
gical therapy offers cures of approximately 90%. Patients to find that extrahippocampal abnormalities also occur
 Chapter 15 Epilepsy 511

in patients with MTS. Findings include atrophy of the Associated findings include the following:

SECTION III
fornix, mamillary body, anterior thalamic nucleus, cin- nn Dilated temporal horn
gulated gyrus, and parahippocampus. Secondary effects nn Atrophy of fornix and mamillary body
include dilatation of the temporal horn (Figures 15-6 nn Increased signal in amygdala
and 15-7). Atrophy of the contralateral cerebellum is nn Increased signal in anterior temporal cortex
also described as crossed cerebellar diaschisis. nn 1H MR spectroscopy in MTS
Other proposed pathogenic processes involved include Proton spectroscopy has demonstrated abnormali-
excitotoxins, particularly glutamate and aspartate. ties of N-acetylaspartate (NAA), a mitochondrial neu-
ronal compound, creatine, and choline in patients with
Diagnosis temporal lobe epilepsy. The abnormalities typically
The combination of clinical, electroencephalographic, consist of reduced NAA signal and increased choline,
and MRI imaging features is usually sufficient for diagno- creatine, and myoinositol signals. These MR spectros-
sis. Three MRI criteria are required for diagnosis of MTS: copy findings are consistent with the histopathologic
1. Atrophy characteristics of reduced neuron cell counts with neu-
2. Signal change (high signal on T2-weighted and ronal dysfunction and increased glial cellularity. Spec-
FLAIR imaging seen most often) troscopy can show reduced NAA peak in asymmetric
3. Derangement of anatomy (loss of digitations of den- MTS and has a lateralizing sensitivity of approximately
tate is useful sign) 80% (Figure 15-8).

Single-Photon Emission Computed Tomography

Table 15-3 Clinical Presentation and Aura Based Single-photon emission computed tomography (SPECT)
on Suspected CNS Location scans show the distribution of blood flow in the brain at
Aura and/or Clinical the time of the injection of a radiotracer, which is injected
­Presentation Suspected CNS Location ictally or interictally. If the radiotracer is injected ictally,
Focal motor seizure, jacksonian Primary motor cortex
focally increased uptake is identified in the affected tem-
seizure, Todd paralysis ­(precentral gyrus) poral lobe (hot focus). If the radiotracer is injected inter-
ictally, the affected temporal lobe demonstrates decreased
Involuntary turning during Motor cortex anterior to
seizure (aversive movement) ­precentral gyrus
uptake compared with that of the rest of the brain (cold
focus) (Figure 15-9). The advantage of SPECT is that it
Somatosensory seizures Primary sensory cortex can used to demonstrate cerebral blood flow during sei-
­(postcentral gyrus)
zure activity.
Bilateral tonic postures Supplementary motor area
Gelastic seizures Hypothalamic region OTHER PATHOLOGIC PROCESSES
Altered affect, crying Frontal gyrus, anterior AND CAUSES OF EPILEPSY
­cingulated gyrus
Apart from hippocampal/MTS, other causes of epilepsy
Auditory auras Region of Heschl gyrus to be considered include the following:
Seizure with olfactory Mesial temporal lobe nn Cerebral neoplasms
or gustatory symptoms nn Vascular malformations
nn Developmental anomalies
Vertigo Insular or parietal cortex
nn Gliosis (including posttraumatic, postsurgical causes)
CNS, Central nervous system. nn Infectious/inflammatory

Cingulate bundle

Fornix

Stria terminalis

Septal region

Olfactory bulb
Anterior commisure
Mammillary bodies
Lateral olfactory stria
Thalamus
Amygdala
Figure 15-3 Schematic limbic system anatomy.
512 Section III  Problem Solving: Disease Categories

Cerebral Neoplasms
Neoplasms represent 2% to 4% of the epileptogenic
CA2
* F causes in the general epilepsy population. The occur-
rence of epileptic seizures in patients suffering from pri-
mary brain tumors, as well as in patients with cerebral
CA3 metastases, varies depending on the tumor entity. Slow-
growing lesions are associated with a higher incidence
CA4 of seizures than rapidly growing lesions. In patients
Dentate Subic with brain metastasis, melanoma is associated with the
CA1
highest likelihood of seizures (Figure 15-10). Lung can-
cer, breast, and gastrointestinal tumor primaries are also
associated with a high frequency of seizures.
Figure 15-4 Schematic diagram of internal architecture of the hip- In the pediatric population, epilepsy-associated
pocampus. Arrow indicates hippocampal fissure. *, alveus; CA1-CA4,
Cornus ammonis; F, fimbria; Subic, subiculum. tumors are more frequently located in the cortex of the
temporal lobes. They are not usually associated with
mass effect or vasogenic edema.
Common epilepsy associated primary brain tumors
include gangliogliomas, dysembryoplastic neuroepithe-
lial tumors (DNETs), pilocytic astrocytomas, pleomorphic
xanthoastrocytomas, and World Health Organization
(WHO) grade II astrocytomas (Figure 15-11).

Gangliogliomas
Gangliogliomas are slowly growing, well-differenti-
ated neuroepithelial tumors composed of a mixture of
neoplastic ganglion and glial cells. They are the most
common mixed neuronal–glial tumor. They are often
partially cystic, often cortically based masses present-
ing in children and young adults with temporal lobe
epilepsy (Figure 15-12). They are usually located in
the temporal lobes but can occur throughout the cere-
brum. They are commonly associated with cortical
dysplasia, and calcification is often present. Little mass
Figure 15-5 Microanatomy of the hippocampus. Microscopic mag- effect or vasogenic edema is seen. Gangliomas dem-
netic resonance imaging at 9.4 T. Neurons in CA1 (Sommer sector) are onstrate variable enhancement pattern and rarely can
most sensitive to ischemia. CA1–CA4, Cornus ammonis; CN, caudate
nucleus; Subic, subiculum. (From Fatterpekar GM, Delman BN, Boonn
have malignant degeneration attributable to its glial
WW, et al. MR microscopy of normal human brain. Magn Reson Imag- component.
ing Clin N Am 2003;11(4):641-653.)
Dysembryoplastic Neuroepithelial Tumors
DNETs are classically seen as a wedge-shaped, well-
defined intracortical partially cystic and nodular lesions.
They present in young patients with a longstanding his-
tory of partial seizures most commonly located in the
temporal lobe, hippocampus, and/or amygdala. Con-
vex lesions tend to cause inner table scalloping. They
have very slow or no growth potential and are unlikely
to recur following resection. Enhancement is a rare and
unusual feature (Figure 15-13).

Pilocytic Astrocytomas
This is the most common primary brain tumor in chil-
dren and is the prototypic WHO grade I neoplasm most
frequently located in the posterior fossa. Although more
than two thirds of all patients demonstrate the classic
imaging manifestation of a cystic mass with an enhanc-
ing mural nodule, approximately 17% of cases can be
predominantly solid masses with minimal to no cyst-
like component. Hence these tumors can be difficult
Figure 15-6 Mesial temporal sclerosis. Note right-sided derange- to differentiate from DNETs and gangliogliomas, espe-
ment of hippocampal anatomy, volume loss, and increased cially when they occur in supratentorial locations and
T2-weighted signal. Compare to normal left side. present as partial seizures.
 Chapter 15 Epilepsy 513

SECTION III
Figure 15-7 Mammillary body atrophy on the right side in a patient with mesial temporal sclerosis. Other associated findings include dilated
temporal horn, atrophy of fornix, increased signal in amygdala, and increased signal in anterior temporal cortex.

NAA

Cho Cr

↓ NAA

A
4.0 3.0 2.0 1.0
B Chemical shift/ppm
Figure 15-8 Magnetic resonance spectroscopy for detecting laterality in mesial temporal sclerosis (MTS). A: Coronal T2-weighted imaging
through mesial temporal lobes with single-voxel spectroscopy over each hippocampal formation. B: Corresponding 1H spectroscopy demonstrat-
ing reduced N-acetylaspartate (NAA) peak in asymmetric MTS. Spectroscopy has a lateralizing sensitivity of approximately 80%. Cho, Choline;
Cr, creatine.
514 Section III  Problem Solving: Disease Categories

Figure 15-9 Single-photon emission computed tomography (SPECT) imaging in a patient with mesial temporal sclerosis performed interic-
tally demonstrating hypoperfusion of the right temporal lobe. SPECT scans show the distribution of blood flow in the brain at the time of injec-
tion of a radiotracer, which is injected ictally or interictally. If the radiotracer is injected ictally, focally increased uptake is identified in the affected
temporal lobe (hot focus). If the radiotracer is injected interictally, the affected temporal lobe demonstrates decreased uptake compared with that
of the rest of the brain (cold focus).

Figure 15-10 Cerebral metastasis. In patients with brain metasta-

sis, melanoma is associated with the highest likelihood of seizures.
 Chapter 15 Epilepsy 515

SECTION III
A B C
Figure 15-11 Low-grade glioma in left medial temporal lobe. Coronal T1-weighted image (A) demonstrates a mass in the left mesial tem-
poral cortex of intermediate to low signal. T2-weighted image (B) and fluid-attenuated inversion recovery image (C) shows hyperintense signal
involving the mass with no surrounding vasogenic edema and little mass effect. Differential diagnosis includes ganglioglioma, dysembryoplastic
neuroepithelial tumor, low-grade astrocytoma, and pleomorphic xanthoastrocytoma.

A B

C D
Figure 15-12 Proven case of ganglioglioma in right medial temporal lobe in an 18-year-old male patient. A: Coronal T1-weighted image fol-
lowing contrast demonstrating subtle lobulated rim enhancement in the same region. B: Coronal fluid-attenuated inversion recovery (FLAIR)
image showing hyperintensity outlining a slightly lobulated cortical mass and marked hyperintensity on T2-weighted (C) and FLAIR (D) images.
516 Section III  Problem Solving: Disease Categories

A B

C D
Figure 15-13 Patient in late teens with typical dysembryoplastic neuroepithelial tumor in right temporal lobe. A, B: Coronal and axial
T2-weighted magnetic resonance images showing a multicystic (bubbly) lesion extending from the mesial right temporal cortex and temporal
pole into the subcortical white matter. C: Axial fluid-attenuated inversion recovery image demonstrating the lesion is hyperintense. D: No signifi-
cant enhancement is seen after contrast.
 Chapter 15 Epilepsy 517

Sturge-Weber Syndrome

SECTION III
Sturge-Weber syndrome is usually a sporadic congenital
neurocutaneous syndrome in which fetal cortical veins
fail to develop normally with ipsilateral facial angioma
in the distribution of ophthalmic branch of the tri-
geminal nerve. This condition does not usually present
a diagnostic challenge because of its stark clinical and
imaging features. Patients can present with variable neu-
rologic symptoms, including intractable seizures and
hemiparesis.
Imaging features are the result of progressive
venous and chronic venous ischemia. Classic tram-
track calcification is often diagnostic on CT. MRI can
demonstrate pial angiomatosis, unilateral atrophy,
hyperintense cortical signal from gliosis, cortical sig-
nal loss to calcification, leptomeningeal enhancement,
and ipsilateral engorged and enhancing choroid plexus
(Figure 15-16).

Malformations of Cortical
Development
Figure 15-14 Pial/parenchymal arterio venous malformation. Developmental malformations constitute 10% to 50%
Axial T2-weighted image showing a large right parietooccipital paren- of pediatric epilepsy cases and 4% to 25% of adult cases.
chymal arteriovenous malformation characterized by large serpentine Malformations of cortical development can be classi-
flow voids. There is no mass effect and the adjacent cortex is atrophic, fied into four categories:
“accommodating” the malformation.
1. Malformations due to abnormal neuronal and glial
proliferation or apoptosis
2. Malformations due to abnormal neuronal migration
Pleomorphic Xanthoastrocytomas 3. Malformations due to abnormal cortical organiza-
Like DNETs and gangliogliomas, pleomorphic xan- tion
thoastrocytomas, a benign subtype of astrocytoma, 4. Malformation of cortical development not otherwise
are found almost exclusively in young adults and classified
most frequently in the temporal lobes. They are WHO Focal cortical dysplasia (FCD) is a distinct subtype
grade II neoplasms and represent less than 1% of all of malformation of cortical development. The findings
astrocytomas. A supratentorial cortical mass with an in FCD can be very subtle and sometimes can only be
adjacent enhancing dural tail should raise suspicion appreciated microscopically. Epilepsy secondary to FCD
of pleomorphic xanthoastrocytoma. Involvement of is thought to be difficult to treat by medication because
the leptomeninges is a feature of this tumor. The deep they have high intrinsic epileptogenicity. It is the most
margin of the tumor may show infiltration of the brain common cause of intractable epilepsy in children,
parenchyma. accounting for the vast majority of surgically treated
cases in children younger than 3 years. Linear subcor-
Vascular Malformations tical T2 hyperintensity extending to the ventricle and
associated with cortical thickening is associated with a
Arteriovenous malformations (Figure 15-14) and cav- particular subtype of FCD containing “balloon cells,”
ernous hemangiomas are the most frequent vascular first described by Taylor et al (type IIB FCD). It is also
malformations causing seizure in epilepsy patients. the most common operated FCD (Figure 15-17). Other
findings include blurring of the gray–white matter junc-
Cavernous Hemangiomas/Cavernomas tion, focal cortical thickening, and gray matter T2 hyper-
Cavernomas are more frequently associated with sei- intensity (Figure 15-18).
zures, particularly partial seizures, than are arteriove- Malformations due to abnormal neuronal migra-
nous malformations. Cavernomas are mulberry-like tion are rarely operated on for seizure control. They
vascular lesions consisting of ectatic endothelium- include the heterotopias, such as band type (Figure
lined channels. Imaging with gradient and suscepti- 15-19), subependymal type (Figure 15-20), lissen-
bility-weighted imaging have made cavernomas even cephalies (Figure 15-21), and schizencephalies ­(Figure
more conspicuous as focal “blooming” low-signal 15-22). Holoprosencephaly is a congenital brain mal-
lesions that may also have “popcorn” high signal formation wherein the forebrain fails to normally
contrast on T2-weighted images (Figure 15-15). Cav- bifurcate of which there are four types: alobar, with
ernoma-related epileptogenicity is thought to be due complete failure of separation; semilobar, the interme-
to chronic, clinically silent, microhemorrhaging. Epi- diate form; lobar, the least severe form; and middle
leptic seizures that are linked to cavernomas are often interhemispheric variant (MIH), also know as syntelen-
medically refractory. cephaly (Figure 15-23).
518 Section III  Problem Solving: Disease Categories

A B

C D
Figure 15-15 Cavernous malformation. A: Axial T1-weighted image demonstrating a large lobulated left temporal mass with multiple hyper-
intense internal regions. B: Axial T2-weighted image showing a rim of low signal involving the same lesion. C, D: Unusually large cavernous
malformation in left hemisphere and multiple other smaller lesions revealed by gradient imaging seen in the right hemisphere.
 Chapter 15 Epilepsy 519

SECTION III
A B C
Figure 15-16 Severe case of right-sided Sturge-Weber syndrome in an 11-year-old male patient with choroidal angioma. A, B: Contrast-
enhanced axial T1 magnetic resonance image showing choroidal angioma (arrow), periorbital enhancement, and enhancement of the enlarged
ipsilateral greater wing of sphenoid. C: Axial T2* gradient-recalled echo showing striking cortical susceptibility from chronic hemosiderin deposi-
tion. Note ipsilateral hemispheric volume loss.

A B
Figure 15-17 Type II focal cortical dysplasia in a 43-year-old female patient. Coronal T2-weighted (A) and coronal fluid-attenuated inversion
recovery (B) magnetic resonance images showing focal cortical thickening of the gray matter in the left frontal region with linear subcortical
hyperintensity extending to the ventricle (arrow).
520 Section III  Problem Solving: Disease Categories

A B C
Figure 15-18 Type I focal cortical dysplasia in the region of the anterior right cingulate gyrus. Magnified coronal fluid-attenuated inversion
recovery (A) and T2-weighted (B) magnetic resonance images showing a subtle hyperintense area in the subcortical white matter of the anterior
right cingulate gyrus and subjacent corpus callosum. C: Axial T2-weighted image demonstrating the subtle finding and blurring of the gray–white
matter junction compared to the normal contralateral side.

A B
Figure 15-19 Band heterotopia, double cortex in an infant. A: Axial T2-weighted image. B: Axial T1-weighted image. Global simplification of
the cortical gyration and bilateral thick subcortical heterotopic gray matter bands are seen. Note shallow sylvian fissures and incidental cavum
septi pellucidi with cavum vergae.
 Chapter 15 Epilepsy 521

SECTION III
A B
Figure 15-20 Nodular subependymal heterotopic gray matter in a 13-year-old male patient. A: Axial T2-weighted image showing bilateral
subependymal heterotopia lining the arium of the lateral ventricles. B: Coronal T1-weighted image showing extensive bilateral subependymal
heterotopia of the left frontal gray matter cortex is thin with shallow sulci. Polymicrogyria is also demonstrated in the right parietal and temporal
regions.

Figure 15-21 Axial T2-weighted image showing classic type 1

l­ issencephaly resulting in a smooth brain surface, shallow sylvian
­fissures, and arrested neuronal migration.
522 Section III  Problem Solving: Disease Categories

A B
Figure 15-22 Closed-lip schizencephaly extending to the right frontal horn. Axial fluid-attenuated inversion recovery (A) and axial T2-weighted
(B) images revealing a “nipple-shaped” outpouching of cerebrospinal fluid from the right frontal horn extending to the subpial surface of the
brain. This tract is lined with gray matter.

A B C
Figure 15-23 Middle interhemispheric variant of holoprosencephaly (syntelencephaly) in a 5-year-old male patient. A: Sagittal T1-weighted
image revealing the absence of the body of the callosum in the region of noncleaved parenchyma. Axial T2-weighted (B) and axial T1-weighted
(C) images showing abnormal communication across the midline with a bridge of gray and white matter.
 Chapter 15 Epilepsy 523

SECTION III
A B C
Figure 15-24 Utility of curved multiplanar reconstruction for assessment of cortical dysplasia. A, B: High-resolution three-dimensional
T1-weighted image dataset can be reconstructed and “rolled out” to aid in the screening of cortical dysplasia (white bracket), which involves almost
the entire right high frontoparietal convexity. C: Original axial T1-weighted image of the same region for comparison showing the abnormality is
less conspicuous to the reader.

A B C
Figure 15-25 Subtle case of hemimegalencephaly. Axial T2-weighted (A) and axial T1-weighted (B) images revealing asymmetrically enlarged
right lateral ventricle and subtle midline shift to the left. C: Curved multiplanar reconstruction of the same patient demonstrates subtle “bulky”
right hemispheric white matter.

Curved reconstructions of the cortical surface from a Tuberous Sclerosis

high-resolution 3D T1-weighted MR sequence can aid Tuberous sclerosis is a multisystemic autosomal domi-
in detecting subtle dysplasias (Figure 15-24) and subtle nant disorder involving primarily the central nervous
cases of hemimegalencephaly (Figure 15-25). system (CNS), the skin, and the kidneys. Neurologic
Microcephaly in itself can be associated with epilepsy features include infantile spasms, intractable epilepsy,
and often is secondary to maternal toxin exposure, such and cognitive disability. In the brain, the characteristic
as smoking or alcohol ingestion during early gestation features are cortical tubers, subependymal nodules, and
(Figure 15-26). giant cell astrocytomas. Cortical tubers are more directly
524 Section III  Problem Solving: Disease Categories

A B
Figure 15-26 Microcephaly. A: Sagittal T1-weighted image demonstrating marked decrease in cranial to facial proportions and a conical head
shape. B: Axial T2-weighted image demonstrating simplification of cortical gyri and a thickened calvarium.

related to epileptogenesis. The junction between gray matter is most commonly seen around the central sulcus,
and white matter in the cortical and subcortical tubers is the interhemispheric fissure and the insula. The greatest
indistinct. Pathologic changes are similar to those seen cortical damage involves the depth of the sulcal spaces
in FCD. Cortical tubers are usually well visualized by while sparing the apex of the convolutions and resulting
MRI as enlarged gyri with atypical shape and abnormal in a mushroom gyric or ulegyric pattern.
signal intensity, mainly involving the subcortical white Posttraumatic epilepsy and seizures are common in
matter (Figure 15-27). Patients with tuberous sclerosis children experiencing traumatic brain injury and predict
must be carefully investigated in order to determine a worse functional outcome. They have an incidence
whether a single epileptogenic area exists because its of about 10% in series of severe head injuries (Figure
surgical removal can yield good seizure control. Two 15-29). Recurring late seizures (relatively remote from
genetic loci for tuberous sclerosis, on chr 9q34 and the initial event) make up the clinical syndrome of post-
16p13.3, form a gene complex product that controls traumatic epilepsy. Susceptibility-weighted imaging is
mammalian target of rapamycin (mTOR) signaling, and a high-spatial-resolution, 3D GRE MR technique with
early trials have shown that mTOR inhibitors such as phase postprocessing that accentuates the paramagnetic
rapamycin could play a dominant roll in the treatment properties of blood products. It is particularly useful
of tuberous sclerosis in the future. and sensitive for detecting extravascular blood products,
as in the setting of diffuse axonal injury, posttraumatic
Gliosis epilepsy, and vascular malformations.

Gliosis is the end result of various focal and diffuse CNS Infection and Inflammatory Causes
injuries. Acute cerebral vascular events are a common
cause of epilepsy in the elderly. Approximately 4% of Seizures can be the earliest clinical sign of a CNS infec-
patients with an acute stroke will have at least one sei- tion, particularly herpes simplex encephalitis (herpes
zure in the early or late period, and half of these patients simplex virus [HSV]) in the elderly population. Tuber-
will develop epilepsy (Figure 15-28). Hemosiderin and culous meningitis or cerebritis and suppurative CNS
gliosis are known to be involved in seizure generation infections are among the most common causes of sei-
and propagation. Therefore, any processes that result in zures worldwide, particularly in developing countries
gliosis and hemosiderin deposition can lead to epilepsy. (Figure 15-30). The seizure may be related to the acute
Causes include operative factor, closed head injury, dif- inflammatory response early in the infectious process
fuse axonal injury, hypoxic–ischemic injury, infarctions, and may be due to gliotic changes in the chronic phase.
and lobar hemorrhage.
Hypoxic–ischemic brain injury sustained in the perina- Herpes Simplex Encephalitis
tal period is a major cause of subsequent chronic disabil- HSV type 1 encephalitis is the most common cause of
ity including seizures. MRI features often reveal symmetric fatal sporadic encephalitis. It can present with variable
lesions within the basal ganglia and thalami with abnor- neurologic symptoms, ranging from altered mental sta-
mal signal intensity in the intervening posterior limb of tus and focal deficits to focal and generalized seizures.
internal capsule. Injury to the cortex and ­subcortical white MRI typically demonstrates hyperintensity in the medial
 Chapter 15 Epilepsy 525

SECTION III
A B

C D
Figure 15-27 Tuberous sclerosis. A, B: Axial postcontrast T1-weighted images. C, D: Axial T2-weighted images. Multiple cortical, subcortical,
and subependymal tubers are seen. The subcortical tubers are best appreciated on the T2-weighted image (arrow in C). A giant cell astrocytoma is
demonstrated adjacent to the left foramen of Monro (C, D).
526 Section III  Problem Solving: Disease Categories

A B
Figure 15-28 Chronic infarction. Seizures may be an early or late complication of cerebral infarcts or hemorrhages. A: Axial T2-weighted image
demonstrating hyperintense signal and cerebral volume loss in the left posterior cerebral artery distribution. B: Diffusion-weighted image showing
no evidence of restriction. Overall, approximately 4% of patients with an acute stroke will have at least one seizure in the early or late period, and
half of them will develop epilepsy.

A B
Figure 15-29 Gliosis secondary to trauma. A: Axial T2-weighted image showing cortical atrophy and gliosis in the left frontal convexity.
B: Gradient imaging revealing old blood product in this region of volume loss.
 Chapter 15 Epilepsy 527

SECTION III
A B C
Figure 15-30 Cerebral abscess. A: Contrast enhanced T1-weighted image showing a smooth ring enhancing the left frontal lobe mass with
extensive vasogenic edema. B: Axial fluid-attenuated inversion recovery image. C: Diffusion restriction is a relatively consistent finding in pyogenic
cerebral abscess.

Figure 15-31 Herpes encephalitis. Abnormal high signal intensity

on fluid-attenuated inversion recovery imaging is seen bilaterally in
the medial temporal lobes, particularly in the uncus and rhinencepha-
lon regions.

temporal, inferior frontal, and cingulate gyrus in a bilat- partial seizures may develop before the cancer becomes
eral and asymmetric pattern (Figure 15-31). Late acute clinically, overt and the patient may be referred to the
and subacute cases can often demonstrate hemorrhage as neurologist as the primary physician. This paraneoplastic
well as restricted diffusion in the involved portion of the syndrome is caused by autoimmune processes triggered
limbic system. Basal ganglia are usually spared, although by the cancer and directed against antigens common to
the cerebral convexity can be involved (Figure 15-32). both the cancer and the nervous system (onconeural
antigens such as anti-HU or anti-Yo in small cell lung
Limbic Encephalitis and ovarian cancers, respectively) (Figure 15-33). MRI
Limbic encephalitis is thought to be a paraneoplastic often presents on T2-weighted imaging with hyperin-
syndrome manifesting with neurologic effects associated tensity in the mesial temporal lobes and limbic system
with extra-CNS tumors. The neurologic disorder and that closely mimics HSV encephalitis but has a different
528 Section III  Problem Solving: Disease Categories

A B C
Figure 15-32 Herpes simplex encephalitis type 1 in a middle-aged female. A: Axial T2-weighted image demonstrating abnormal hyperintensity
in the temporal and insular cortex that is bilaterally greater on the right, sparing the lentiform nucleus. B: Diffusion-weighted image showing
cortical restrictions in the right insular, temporal opercula, and cingulate gyrus. C: Axial T1-weighted image with contrast showing striking cortical
enhancement in the right temporal lobe and insular but also subtly on the left side. Enhancing lesions are also seen in the cingulate gyri.

A B C
Figure 15-33 Subacute limbic encephalitis and N-methyl-d-aspartate receptor antibodies in a 46-year-old male patient with lung cancer. Axial
T2-weighted (A) and axial fluid-attenuated inversion recovery (B) magnetic resonance images demonstrating striking atrophy in the temporal
lobes and hyperintense signal in the white matter. C: Coronal T2-weighted image best demonstrates the expanded temporal horns reflecting the
subacute nature of the presentation.

clinical course due to its subacute or chronic presenta- e­ pisode. Focal swelling of gyri can be seen early during
tion (Figure 15-34). Unlike HSV encephalitis, hemor- the course of the disorder.
rhage is not seen in limbic encephalitis.
PITFALLS IN IMAGING
Rasmussen Encephalitis
A chronic encephalitis called Rasmussen encephalitis There are several common pitfalls to be aware of in order
can be seen in children and young adults as progres- to avoid overdiagnosing or underdiagnosing imaging
sive unilateral cortical atrophy, with enlargement of the findings suggestive of focal lesions.
ventricular system seen over time. It is one of the causes If head rotation is present, assessment of hippocam-
of Dyke-Davidoff-Masson syndrome (Figure 15-35). pal symmetry must be performed by comparing com-
Degeneration of the corticopontocerebellar fibers can patible coronal hippocampal sections in the setting of
also result in contralateral cerebellar diaschisis. The con- MTS. Nonrotation can be quickly confirmed by noting
dition is of uncertain etiology, although autoimmune if the cochlea and internal auditory meatus bilaterally
and prior viral infections are postulated, and in many are in the same coronal image (Figure 15-36). Another
cases the condition is preceded by an inflammatory potential pitfall in assessing patients for MTS is the
 Chapter 15 Epilepsy 529

SECTION III
A B
Figure 15-34 Limbic encephalitis in a patient with multiple myeloma. A: Axial fluid-attenuated inversion recovery image showing high signal
intensity in both medial temporal lobes. B: Axial T2-weighted image demonstrating several multiple myeloma skull lesions.

A B
Figure 15-35 Rasmussen encephalitis in a 20-year-old female patient with a history of refractory epilepsy. A: Axial fluid-attenuated inversion
recovery magnetic resonance image showing marked enlargement of the left hemispheric sulci and ipsilateral lateral ventricle. Increased signal is
seen in the underlying white matter. B: Coronal T2-weighted image demonstrating crossed cerebellar diaschisis.
530 Section III  Problem Solving: Disease Categories

B
Figure 15-36 Confirmation of nonrotation of coronal images
through the temporal lobe. Check that the cochlea (arrows in A) and
internal auditory meatus (arrows in B) are in the same coronal image.

A B
Figure 15-37 Asymmetric temporal horns. This is a potential pitfall in assessing patients for mesial temporal sclerosis. A: Coronal T2-weighted
image showing asymmetry of the temporal horns due to a choroid fissure cyst, an incidental normal variant. Note the absence of increased signal
in the hippocampus or derangement of its anatomy. B: Coronal T1-weighted image.

normal variant of asymmetry of the temporal horns reversible imaging finding and support the diagnosis
(Figure 15-37). (Figure 15-39).
Postictal changes can present as focal or multifocal An important pitfall to avoid relates to dual pathol-
hyperintense abnormalities of the cortex or hippocam- ogy, which is defined as the coexistence of hippocampal
pus on long TR imaging and as restricted diffusion on sclerosis with another epileptogenic substrate. It is easy to
diffusion-weighted imaging (Figure 15-38). Caution focus on an obvious lesion and neglect assessment of the
should be exercised in interpreting findings and recom- hippocampus. Coincidental hippocampal sclerosis is not
mending invasive studies for actively seizing patients. infrequent, especially with developmental anomalies.
Transient lesions can be seen in the splenium of the
corpus callosum. This particular lesion is thought to SUPPLEMENTARY AND
result from either frequent seizures or abrupt changes
COMPLEMENTARY TESTS
in antiepileptic drug concentrations that may cause
cytotoxic edema in the splenium. Slight mass effect Subdural grid arrays are used when seizure activity
from cortical edema way be mistaken for a neoplastic cannot be located by ictal scalp recordings and when
lesion, and follow-up imaging is crucial to confirm this functional cortical mapping is required before surgery
 Chapter 15 Epilepsy 531

SECTION III
A B C
Figure 15-38 Status epilepticus in a 9-year-old male patient immediately prior to imaging. A: Axial T2-weighted image showing hyperinten-
sity in the parietooccipital regions bilaterally in a cortical and subcortical distribution. There is sulcal effacement secondary to cortical edema.
Diffusion-weighted image (B) and apparent diffusion coefficient image (C) demonstrate diffusion restriction in the affected areas.

A B C

D E F
Figure 15-39 Postseizure edema in a 68-year-old patient. Axial T2-weighted (A), axial fluid-attenuated inversion recovery (B), and coronal
T2-weighted (C) images show an asymmetrically enlarged left mesial temporal cortex and uncus from a 2006 study performed soon after an epi-
sode of seizure (arrows). D–F: Magnetic resonance images from a follow-up study in 2008 reveal resolution of cortical edema.
532 Section III  Problem Solving: Disease Categories

e­ pileptogenic activity. For example, MR/FDG-PET in

patients with tuberous sclerosis who present with medi-
cally refractory epilepsy and multiple tubers can demon-
strate tubers with epileptogenic activity, seen as regions
of hypometabolic activity in the tubers during interictal
imaging.

Suggested Readings
Bote RP, Blázquez-Llorca L, Fernández-Gil MA, Alonso-Nanclares L, Muñoz A,
De Felipe J. Hippocampal sclerosis: histopathology substrate and magnetic
resonance imaging. Semin Ultrasound CT MR. 2008;29(1):2-14.
Cepeda C, André VM, Levine MS, et al. Epileptogenesis in pediatric cortical
dysplasia: the dysmature cerebral developmental hypothesis. Epilepsy Behav.
2006;9(2):219-235.
Chan S, Erickson JK, Yoon SS. Limbic system abnormalities associated with
mesial temporal sclerosis: a model of chronic cerebral changes due to
seizures. Radiographics. 1997;17(5):1095-1110.
Concha L, Gross DW, Beaulieu C. Diffusion tensor tractography of the limbic
system. AJNR Am J Neuroradiol. 2005;26(9):2267-2274.
Duncan JS. Imaging and epilepsy. Brain. 1997;120(Pt 2):339-377.
El Kamar FG, Posner JB. Brain metastases. Semin Neurol. 2004;24(4):347-362.
Engel Jr J. Surgery for seizures. N Engl J Med. 1996;334(10):647-652.
Ferroli P, Casazza M, Marras C, Mendola C, Franzini A, Broggi G. Cerebral
cavernomas and seizures: a retrospective study on 163 patients who
underwent pure lesionectomy. Neurol Sci. 2006;26(6):390-394.
Hogan RE, Wang L, Bertrand ME, et al. Predictive value of hippocampal MR
imaging-based high-dimensional mapping in mesial temporal epilepsy:
Figure 15-40 Subdural platinum grid electrodes in situ over the preliminary findings. AJNR Am J Neuroradiol. 2006;27(10):2149-2154.
right cerebral hemisphere for identification of the seizure-onset zone Maehara T. Neuroimaging of epilepsy. Neuropathology. 2007;27(6):585-593.
and mapping of language and motor cortex. Ng YT, McGregor AL, Wheless JW. Magnetic resonance imaging detection of
mesial temporal sclerosis in children. Pediatr Neurol. 2004;30(2):81-85.
Oikawa H, Sasaki M, Tamakawa Y, Kamei A. The circuit of Papez in mesial
temporal sclerosis: MRI. Neuroradiology. 2001;43(3):205-210.
(Figure 15-40). Advanced noninvasive neuroimaging Ozturk A, Yousem DM, Mahmood A, El Sayed S. Prevalence of asymmetry of
mamillary body and fornix size on MR imaging. AJNR Am J Neuroradiol.
techniques with multimodality imaging are increasingly 2008;29(2):384-387.
being used, particularly in cases of pediatric epilepsy. Papez JW. A proposed mechanism of emotion. 1937. J Neuropsychiatry Clin
These approaches include fluorodeoxyglucose-positron Neurosci. 1995;7(1):103-112.
Rastogi S, Lee C, Salamon N. Neuroimaging in pediatric epilepsy: a
emission tomography (FDG-PET), magnetoencephalog- multimodality approach. Radiographics. 2008;28(4):1079-1095.
raphy, diffusion tensor imaging, and magnetic source Strzelczyk A, Reese JP, Dodel R, Hamer HM. Cost of epilepsy: a systematic
imaging in combination with conventional MRI. Tech- review. Pharmacoeconomics. 2008;26(6):463-476.
Taylor DC, Falconer MA, Bruton CJ, Corsellis JA. Focal dysplasia of the cerebral
niques such as MR/FDG-PET fusion imaging allows cortex in epilepsy. J Neurol Neurosurg Psychiatry. 1971;34(4):369-387.
the detection of many subtle abnormalities that may Urbach H. Imaging of the epilepsies. Eur Radiol. 2005;15(3):494-500.
Villemure JG, de Tribolet N. Epilepsy in patients with central nervous system
go undetected with conventional MRI. Furthermore, tumors. Curr Opin Neurol. 1996;9(6):424-428.
these techniques can guide surgical resection in patients Willmore LJ. Post-traumatic epilepsy: cellular mechanisms and implications for
with multiple lesions by selecting those with greatest treatment. Epilepsia. 1990;3(Suppl 31):S67-S73.
 chapter 16

Neuroimaging of Pediatric
Hypoxic–Ischemic Injury
Andre D. Furtado, Saulo Lacerda, and Thomas P. Naidich

most of the diagnostic information. Perfusion weighted

WHY IMAGING?
imaging (PWI) can be helpful to define the penumbra
Hypoxic–ischemic injury in preterm or full-term neo- (“area at risk”) in children with focal ischemic stroke.
nates is a major cause cerebral palsy, seizures, and cog-
nitive disorders. Additionally, preterm neonates with FETAL AND NEONATAL HYPOXIC–
periventricular leukomalacia also present spastic para- ISCHEMIC BRAIN INJURY
paresis. In older children, the incidence of ischemic
stroke is higher than once suspected. Imaging should be Imaging findings in hypoxic–ischemic brain injury are
performed when hypoxic-ischemic injury is suspected in influenced by brain maturity of the newborn infant as
infants, toddlers, or children. well as severity and duration of insult. The gestational
age is one of the most important factors when determin-
ing the pattern of the brain damage.
WHO NEEDS IMAGING?
1. Very-low-birthweight preterm neonates. These neo- Hypoxic–Ischemic Injury in Preterm
nates are at risk for neurodevelopmental disability. Neonates (<36 Weeks’ Gestational
Intraventricular hemorrhage is a major cause of adverse Age)
outcome. Clinical manifestations of hypoxic-ischemic
injury in preterm neonates include spastic paraplegia, In premature infants, the injury occurs mainly in the
cerebral palsy, seizures, and cognitive disorders. deep areas of the brain. The periventricular white matter
2. Neonates with clinical hypoxic-ischemic encepha- is more susceptible to hypoxic–ischemic injury because
lopathy (HIE). Neonatal encephalopathy is a syn- it receives blood supply from terminal circulation
drome of neurologic dysfunction including difficulty between the superficial and deep branches of the middle
to initiate and maintain respiration, depression of cerebral artery. Diffuse noncystic white matter changes
tone and reflexes, subnormal level of consciousness, are one of the most common imaging findings.
and seizures. Neonates with stage 2 or 3 encephalop- When the insult occurs from 24 to 26 weeks of ges-
athies are at risk to have cerebral injury and should tational age, irregularly enlarged ventricular trigones
be imaged (Table 16-1). with minimal periventricular gliosis is most frequently
3. Any infant or child with new neurologic deficit. Imag- seen. When the insult occurs from 28 to 32 weeks, the
ing is indicated to any pediatric patient with new neu- typical finding is variably dilated ventricles with more
rologic deficit, especially if stroke is suspected. evident periventricular gliosis. Insults at 36 weeks char-
acteristically result in cortical and subcortical atrophy
PROBLEM SOLVING: HOW TO with periventricular gliosis. Early diagnosis of severe
hypoxic–ischemic injury is particularly important in
IMAGE/WHICH IMAGING?
the immediate postnatal period, when decisions about
Cerebral ultrasound (US) can be useful for detection of active life support must be made.
periventricular leukoencephalomalacia (PVL) and ger-
minal matrix hemorrhage (GMH). It is considered less Cranial Sonography in Hypoxic–Ischemic Injury
sensitive than magnetic resonance (MR) for detection of in Preterm Neonates
white matter changes and is less sensitive than CT in the Initially, PVL presents as periventricular areas of
detection of small subependymal hemorrhage. increased echogenicity that may progress to cystic
CT scanning is an alternative to magnetic resonance changes after 3 to 4 weeks. Preterm neonates may have
imaging (MRI) for excluding hemorrhage and has some mild periventricular increased echogenicity of uncer-
prognostic information. CT should be performed with tain significance (Figure 16-1); however, periventricu-
the low-dose protocol during the perinatal period, lar white matter as echogenic as the choroid plexus or
which results in a lower signal-to-noise ratio. asymmetric white matter hyperechogenicity should be
MRI is the best modality for diagnosis and prognosis considered abnormal (Figure 16-2). Cysts are identified
of hypoxic–ischemic injury. T1, T2, gradient echo, and as areas with echogenicity similar to that of cerebro-
diffusion-weighted imaging (DWI) sequences provide spinal fluid (CSF). Of note, congenital periventricular

533
534 Section III  Problem Solving: Disease Categories

cysts and frontal horn coarctation may simulate PVL ­ ormal myelinization. CT can demonstrate late findings
n
(Figure 16-3). With more severe insult, the areas of echo- of PVL with reduction in volume of the periventricular
genicity may extend into the subcortical white matter white matter, ventriculomegaly particularly with dilata-
and develop into extensive periventricular and subcorti- tion of the trigones, and irregular ventricular walls. CT
cal cystic lesions. To confirm the presence of a structural should be avoided in neonates given the associated ion-
abnormality rather than an artifact, the periventricular izing radiation exposure. A low-dose radiation protocol
hyperechogenicity and the cysts should be seen in both for neonates should always be applied.
coronal and parasagittal planes.
MRI in Hypoxic–Ischemic Injury in Preterm
Computed Tomography in Hypoxic–Ischemic Neonates
Injury in Preterm Neonates Maintenance of body temperature and oxygen satura-
Although head computed tomography (CT) is very sen- tion greater than 95% is critical during neonatal MR
sitive to subependymal hemorrhage, it provides little examination. MR-compatible incubators have been
information during the early stages of PVL due to its developed to provide a less stressful environment for
limited differentiation of periventricular injury and extreme preterm neonates. Infants may be sedated with
50 or 75 mg/kg of chloral hydrate orally prior to the
Table 16-1 C
 linical Stages of Neonatal MR examination if not contraindicated. Heart rate and
­Encephalopathy transcutaneous oxygen saturation should always be
monitored during the scanning time and supplemental
Stage of Neonatal oxygen should be available if necessary. Dedicated head
Encephalopathy Clinical Criteria
coils has made possible high resolution images of the
1 <24 hours with hyperalertness neonatal brain in a reasonable scanning time.
Moro and stretch reflexes MR findings in premature neonates with PVL include
Sympathetic effects decreased signal intensity on T1-weighted images and
Normal electroencephalogram
increased signal intensity on T2-weighted images involv-
2 Obtundation ing the periventricular white matter (Figure 16-4), which
Hypotonia below a certain threshold is of unclear clinical relevance.
Decreased spontaneous movements
Some neonates may progress to periventricular cysts
3 Stupor (­Figure 16-5). Cystic lesions are defined as areas with
Flaccidity signal intensity identical to that of CSF in all sequences.
Seizures
Suppressed brainstem and autonomic In more severe cases, intraparenchymal hemorrhagic or
functions cystic lesions may involve both periventricular and sub-
Electroencephalogram with isopoten- cortical white matter. Of note, dilated perivascular spaces
tial or infrequent periodic discharges in the peritrigonal white matter may resemble cystic PVL,
Patients with grade 2 or 3 encephalopathy usually have a poor prognosis and however, without atrophy (Figure 16-6).
should undergo imaging.

Figure 16-1 Normal periventricular echogenicity in a

5-day-old 30-week preterm neonate. Cranial US demon-
strates normal periventricular white matter echogenicity
(arrows) that are less echogenic than the choroid plexus (*).
Chapter 16 Neuroimaging of Pediatric Hypoxic–Ischemic Injury 535

SECTION III
Figure 16-2 Periventricular leukoencephalomalacia in
a 6-day-old 25-week preterm neonate. Cranial US dem-
onstrates asymmetric periventricular white matter echo-
genicity (arrows). The right periventricular white matter is as
echogenic as the choroid plexus (*). Note hyperechogenic
foci in the right choroid plexus, suggestive of hemorrhage
(arrowheads).

Figure 16-3 Congenital periventricular cysts

in a 5-day-old 30-week preterm neonate. Cra-
nial US demonstrates bilateral well-defined areas
with echogenicity similar to that of cerebrospinal
fluid in the periventricular white matter (arrows).
These congenital cysts typically occur below the
level of the ventricular angles.
536 Section III  Problem Solving: Disease Categories

Figure 16-4 Periventricular increased signal intensity on

coronal T2 (5610/159) image of a 37-day-old 28-week preterm
neonate. This finding is of uncertain clinical significance.

Figure 16-5 Periventricular leu-

koencephalomalacia in a 3-year-
old 29-week preterm neonate.
Axial T2 fluid-attenuated inversion
recovery (10002/101.4) (A) and
axial T2 (4700/111.6) (B) images
show area of T2 hyperintensity
and cyst formation in the periven-
tricular white matter bilaterally
(arrows).

MRS in PVL (ADC) values may be evident from a few hours to almost
It has been reported that a lactate peak may be seen in 1 week after the insult. Because the ADC values change
preterm infants and infants who are small for their ges- with time, pseudonormalization may occur if imaging
tational age, as well as in cases of head trauma, inborn is performed after 8 or 10 days. Elevated ADC values
errors of metabolism, or mitochondrial disease. It has may not be apparent for two to three weeks. Therefore,
also been reported that pentobarbital commonly used in lack of abnormality on DWI and normal ADC does not
neonates with HIE can lower lactate/choline and lactate/ exclude PVL.
N-acetylaspartate (NAA) ratios in the basal ganglia of
premature neonates. Therefore, it seems that the role of Germinal Matrix Hemorrhage
MRS in hypoxic–ischemic injury of preterm infants is still
unclear. Germinal matrix is the subependymal region of neu-
ronal precursors before their migration to the cortex.
DWI in PVL Premature and low-birthweight newborns are at risk for
The time of the hypoxic-ischemic event in PVL is usually germinal matrix hemorrhage (GMH). Birth trauma and
not clear. It has been reported that reduced diffusion hypoxic–ischemic events are the most frequent causes
and abnormally decreased apparent diffusion ­coefficient of GMH. Clinically, intraventricular hemorrhage is
 Chapter 16 Neuroimaging of Pediatric Hypoxic–Ischemic Injury 537

SECTION III
Figure 16-6 Enlarged perivascu-
lar spaces in an 8-year-old 27-week
preterm neonate resembling peri-
ventricular leukomalacia. Axial
T2 (4700/111.6) (A) and axial T2
fluid-attenuated inversion recovery
(10002/101.4) (B) images show
cluster of cyst formations in the
parietal white matter bilaterally
without evidence of gliosis of vol-
ume loss (arrows).

Table 16-2 C
 lassification of Germinal Matrix MRI in GMH
­Hemorrhage GMH typically have increased signal intensity on
Grade Definition
T1-weighted images and decreased signal intensity
on T2-weighted images, but signal intensity can vary.
I Hemorrhage confined to germinal matrix ­Gradient-recalled echo and susceptibility-weighted imag-
II Hemorrhage extents to ventricles ing may demonstrate blood products (ferritin/hemosid-
erin) deposition (Figure 16-9). DWI can be helpful as late
III Hemorrhage extents to ventricles with
­ventriculomegaly
acute or subacute blood clots may demonstrate reduced
diffusibility. Neonates with acute large intraventricular
IV Hemorrhage into cerebral parenchyma hemorrhages may have fluid-fluid level in the lateral ven-
tricle. Hydrocephalus and parenchymal atrophy can be
seen as a complication of high grade GMH (Figure 16-10).
Cerebellar hemorrhage is usually under recognized
f­ requently associated with a drop in the hematocrit. The in preterm neonates. It often occurs concomitantly with
most used classification for GMH is listed in Table 16-2. supratentorial hemorrhage and is associated with high
Grade 1 and 2 GMH are associated with a low mortal- mortality. US is particularly insensitive for cerebellar
ity rate whereas grade 3 and 4 are associated with a poor hemorrhage compared to MRI. Cerebellar hemorrhage
neurodevelopment outcome and a high mortality rate. may also be a manifestation of an associated blood dis-
GMH typically occurs in the first seven days after birth order. Hemorrhagic foci without PVL are suggestive of
with a peak on day 3. Early GMH has a higher mortality blood disorder rather than a hypoxic–ischemic injury.
rate whereas late GMH has a more benign prognosis.
Late GMH occurs in less than 5% of the cases and can be Profound Asphyxia in Full-Term
of minor severity or clinically silent. Neonates (>36 Weeks’ Gestational
Age)
US in GMH
US scans show unilateral or bilateral hyperechoic hemor- Profound asphyxia in full-term neonates is associated
rhagic material in the caudothalamic groove. Depending with injury to the thalami, basal ganglia, and brainstem.
on the severity, this may extend into the lateral ventricles Full-term neonates may also have cortical and subcorti-
and cause hydrocephalus (Figures 16-7 and 16-8). Initially, cal involvement and atrophy with more severe insults.
decreased resistive index (RI) may be seen on Doppler Grade 2 or 3 encephalopathy in term infants are known
US; however, sustained asphyxia with significant intracra- to have a high incidence of neurologic damage and
nial hemorrhage or diffuse cerebral edema may result in should undergo imaging.
increased RI, which is indicative of a poor outcome. Other findings from a difficult delivery such as caput
succedaneum, cephalohematoma, subdural hematoma,
CT in GMH or subarachnoid or intracranial hemorrhages may be
CT provides a rapid mode of cranial screening for a GMH present.
hemorrhage in neonates without the need for sedation;
however, it is the least sensitive modality for evaluation Transcranial US in Profound Asphyxia
PVL and is disadvantaged due to the exposure to ioniz- Sagittal sonogram of a term neonate with hypoxic–
ing radiation. CT can be useful when suspicion for ger- ischemic encephalopathy shows hyperechogenicity in
minal matrix hemorrhage is high and US is equivocal, the basal ganglia and thalami (Figure 16-11). It may be
particularly if MR is contraindicated or not available. transient or persistent and may progress to cavitation.
538 Section III  Problem Solving: Disease Categories

A B

Figure 16-7 Grade 1 and 2 GMH. Coronal

(A) and sagittal (B) cranial US demonstrates nod-
ular hyperechogenicity (arrows) in the right cau-
dothalamic groove consistent with grade 1 GMH.
Coronal (C) and sagittal (D) cranial US images of
a different preterm neonate demonstrate exten-
sion into the frontal (arrows) and occipital (*)
horns of right lateral ventricle without significant C D
hydrocephalus, consistent with grade 2 GMH.

A B

Figure 16-8 Grade 3 and 4 GMH. Coronal

(A) and sagittal (B) cranial US images demon-
strate nodular hyperechogenicity extending into
lateral (arrows) and third (curved arrow) ventricles
with associated hydrocephalus (*), consistent
with grade 3 GMH. Coronal (C and D) cranial US
images of a different preterm neonate demonstrate
intraparenchymal hemorrhage (arrows), consistent
with grade 4 GMH. Note that besides the hydro-
cephalus (*), the right lateral ventricle is irregularly
shaped (curved arrow), suggestive of porencephalic C D
cyst secondary to intraparenchymal hemorrhage.
 Chapter 16 Neuroimaging of Pediatric Hypoxic–Ischemic Injury 539

SECTION III
Figure 16-10 Porencephalic cyst secondary to intraparenchymal
hemorrhage in a 5-year-old boy with history of 27-week premature
birth. Coronal T2 (5000/1127.2) image demonstrates ex vacuo dilata-
tion of the left lateral ventricle due to grade 4 GMH (arrow). Note lack
of midline shift, mass effect, or transependymal edema, which would
be seen in unilateral hydrocephalus.

Figure 16-9 Intraventricular hemorrhage. Axial gradient-recalled

echo (1770/3.9; flip angle = 30°) image demonstrates susceptibility
effect from blood products in the choroid plexuses bilaterally (arrows).

A B
Figure 16-11 Profound asphyxia in a full-term neonate. Coronal (A) and sagittal (B) cranial US demonstrates hyperechogenicity in the basal
ganglia and thalami (arrows).

CT in Profound Asphyxia MRI in Profound Asphyxia

Although CT is less sensitive than US and particularly MRI typically shows increased signal intensity on
RM, low attenuation related to edema or high attenua- T1-weighted images, involving the ventral lateral
tion related to blood or calcium may be appreciated in ­thalami (Figure 16-12), posterolateral lentiform nuclei
the thalami, basal ganglia, and brainstem. (Figure 16-13), posterior mesencephali (Figure 16-14),
540 Section III  Problem Solving: Disease Categories

Figure 16-12 Profound hypoxic–ischemic injury in a 1-day-old full-

term neonate. Axial T1 (433/9) image showing area of signal hyper-
intensity involving the basal ganglia and thalami bilaterally (arrows).
Note some cortical involvement in the occipital lobes (arrowheads).

Figure 16-13 Profound hypoxic–

ischemic injury in a 5-day-old full-
term neonate. Axial T1 (400/9)
image showing area of signal
hyperintensity (arrows) involving
the lentiform nucleus and thalami
bilaterally (A) and central gyri
bilaterally (B). Note right tem-
poroparietal cephalohematoma A B
(curved arrows).

Figure 16-14 Profound hypoxic–ischemic injury in a 1-day-old full-

term neonate. Sagittal T1 (450/9) image showing area of signal hyperin-
tensity involving the posterior brainstem (arrow) and thalami (arrowhead).
 Chapter 16 Neuroimaging of Pediatric Hypoxic–Ischemic Injury 541

and hippocampi. Cavitation may be present. Progres- Transcranial US in Partial Prolonged

SECTION III
sion with involvement of the lateral geniculate nuclei Hypoxia–Ischemia
and perirolandic cerebral cortex may occur. MR may US is particularly insensitive in infants with prolonged
show no abnormality if imaging is performed to early, hypoxic-ischemic injury because of its limited visualization
particularly in the first 6 hours. of the posterior parasagittal regions of the parietal lobes,
where most of the abnormalities related to partial pro-
MRS in Profound Asphyxia longed hypoxia-ischemia occur. It may show effacement of
Although some authors have documented a minimally the gray–white junction from cytotoxic edema or volume
elevated Lactate/Choline ratio (<0.15) in normal loss from chronic gliosis in the anterior watershed zones.
term neonates, others have advocated that differently
from preterm infants and infants that are small for CT in Partial Prolonged Hypoxia–Ischemia
gestational age, MRS performed in the first 24 hours It is possible to appreciate hypoattenuation with vol-
is sensitive to hypoxia–ischemia in term neonates. It ume expansion from edema (Figure 16-17, A) or with
has been reported that the lactate peak rises during volume loss from chronic gliosis involving the water-
hypoxia–ischemia, is rapidly cleared on resuscita- shed distribution.
tion, and after 12 to 24 hours a secondary lactate peak
appears. Depending on the severity of the insult, ele- MRI in Partial Prolonged Hypoxia–Ischemia
vated lactate and diminished NAA tends to worsen in MRI shows decreased signal intensity on T1-weighted
the first 5 days and then normalize. Persistent elevated images and increased signal intensity on T2-weighted
lactate for more than 48 hours may be a sign of adverse images with volume expansion from edema (Figure
prognosis. 16-17, B and C), or with volume loss from chronic gliosis.

DWI in Profound Asphyxia MRS in Partial Prolonged Hypoxia–Ischemia

DWI performed on day 3 of life, in term newborns with Patients with partial prolonged hypoxia-ischemia may
neonatal encephalopathy, is considered the most sen- have elevated Lactate/Choline ratios in the white matter.
sitive technique for assessing hypoxic-ischemic brain
injury. DWI may be abnormal in the cortex, basal DWI in Partial Prolonged Hypoxia–Ischemia
nuclei, or white matter before conventional MRI. It has In the acute phase, DWI may demonstrate areas of
been that DWI may not reveal the extent of the injury or restricted diffusion with low ADC values in the parasag-
late neuronal damage, related at least in part to cellular ittal watershed zones (Figure 16-17, D).
apoptosis (Figure 16-15).
ISCHEMIC STROKE DURING
Multicystic Encephalomalacia INFANCY AND CHILDHOOD
Multicystic encephalomalacia represents the result of Arterial strokes in children can be attributed to a variety of
widespread brain necrosis that develops into cystic causes including cardiac anomalies, intracranial vasculop-
lesions (Figure 16-16). Multicystic encephalomalacia athies, arterial dissection, migrainous vasospasm, mito-
usually results from severe hypoxic–ischemic brain chondriopathy, and hypercoagulable states, such as factor
damage, particularly late in the third trimester of ges- V Leiden, protein C, protein S, anticardiolipin antibody,
tation and birth. It is generally due to severe asphyxia polycythemia, sepsis, tumor, trauma, disseminated intra-
or hypotension in term or near-term neonates. Less vascular coagulation, and metabolic disorders. Imaging is
frequently, it is due to infection, trauma, or other usually used to differentiate ischemic versus hemorrhagic
injuries. stroke, assess the extension of the infarct, and sometimes
suggest a specific cause. Vascular imaging can display arte-
Partial Prolonged Hypoxia–Ischemia rial dissection or venous thrombosis. Uni- or ­bilateral tha-
lamic infarcts can occur in meningitis. Multiple infarcts
In partial prolonged hypoxia, vital brain areas, such as involving predominantly the anterior circulation can be
the brainstem, thalami, basal ganglia, hippocampus, related to embolic storm (Figure 16-18) and multiple
and cerebellum are preserved at the expense of less infarcts not strict to a vascular distribution involving pre-
metabolically active areas, such as the cerebral cortex dominantly the posterior lobes can be related to mito-
and white matter. The watershed zones are particularly chondrial myopathy, encephalopathy, lactic acidosis, and
vulnerable because they are relatively hypoperfused stroke (MELAS) syndrome. Leigh’s disease, also known
when blood is shunted to the vital, more central areas. as subacute necrotizing encephalomyelopathy, predomi-
Similar findings can also result as a consequence of nantly involves the basal nuclei, thalami, dorsal mesen-
­hypotension. cephalon, pons and medulla bilaterally.
The subcortical white matter almost always undergoes
atrophy and gliosis. As a result, the most typical imaging Cranial US in Ischemic Stroke During Infancy
finding in these patients is ulegyria (“­mushroom-shaped and Childhood
gyri”), which sometimes becomes an epileptogenic In infants with open fontanelle, US demonstrates loss of
focus. This finding is most frequently seen in the triple gray–white differentiation seen in early strokes. Edame
watershed zone at the border zone of the anterior, mid- appears as hyperechogenicity in the basal ganglia and
dle, and posterior cerebral arteries. cortex with signs of volume expansion. Hemorrhage
542 Section III  Problem Solving: Disease Categories

A B

Figure 16-15 Late hypoxic–ischemic brain

damage in a full-term neonate. Axial DWI
(A) and ADC (B) images obtained in the first
24 hours after profound hypoxia–ischemia
shows reduced diffusion and decreased ADC
values in the ventral lateral thalami bilaterally
(arrows). Axial DWI (C) and ADC (D) images
72 hours after the hypoxic–ischemic event
demonstrate widespread abnormality involv-
ing the cortex and white matter of both hemi- C D
spheres (arrows).

Figure 16-16 Multicystic en­­

cephalomalacia in a 1-year-old
boy full-term neonate. Axial
T1-weighted (433/9) (A) and T2
(5500/131.5) (B) images showing
diffuse cystic transformation of
the cortex and subcortical white A B
matter.

should be suspected if foci or focal areas with increased CT in Ischemic Stroke During Infancy
hyperechogenicity are noted. US is not sensitive for and Childhood
small and peripheral strokes. On follow-up studies, US A low-dose radiation protocol is generally warranted. The
shows hyperechogenicity with volume loss and possible temporal and occipital poles are particularly sensitive to
cystic areas. artifact formation during low-dose radiation protocols.
 Chapter 16 Neuroimaging of Pediatric Hypoxic–Ischemic Injury 543

SECTION III
A B

C D
Figure 16-17 Partial prolonged hypoxic–ischemic insult in a 1-day-old girl. Noncontrast computed tomography axial image (A) demonstrat-
ing areas of hypoattenuation and some loss of gray–white matter differentiation in the parasagittal watershed zones bilaterally (arrows). Note right
temporal cephalohematoma (arrowhead). T1-weighted (B) and T2 fluid-attenuated inversion recovery (C) images of a different 1-day-old girl who
suffered partial prolonged hypoxic–ischemic injury showing signal hyperintensity and involving the cortex in the parasagittal watershed zones
bilaterally. D: Diffusion-weighted imaging displaying high signal.

CT carries lower sensitivity to ischemic changes com- In incomplete infarction, cortical luxury perfusion may
pared with MRI but has good sensitivity and specificity enhance within 2 to 4 hours after the stroke.
for ruling out intracranial hemorrhage. CT findings are
similar to those of stroke in adults. Effacement of len- DWI in Ischemic Stroke During Infancy
tiform nucleus or insular ribbon, hypoattenuation in a and Childhood
vascular territory, tissue swelling, loss of gray–white mat- In general, high signal on DWI with corresponding low
ter differentiation, and dense thrombosed vessels may be ADC values may be found as early as 30 minutes after
found. stroke onset. Transition from decreasing to increasing
ADC is estimated at 18 hours after stroke onset. Pseudo-
MRI in Ischemic Stroke During Infancy normalization is estimated to occur around 8 days after
and Childhood infarct.
MRI is an alternative to CT to avoid ionizing radia-
tion exposure in pediatric patients. A few hours after PWI in Ischemic Stroke During Infancy
stroke onset, a loss of arterial signal void is sometimes and Childhood
observed. After 1 to 2 hours, patients with ischemic PWI using first-pass contrast bolus injection or spin
strokes generally demonstrate T1-weighted subtle efface- tagging of protons in the water in blood reveals reduc-
ment of the sulci due to cytotoxic edema. Around 4 to 8 tions of cerebral blood flow and cerebral blood vol-
hours, T2-weighted imaging shows hyperintense signal ume and an increased mean transit time of blood.
due to both cytotoxic and vasogenic edema. In com- Matched between the diffusion and perfusion abnor-
plete infarction, cortical laminar necrosis enhances 5 to malities correlate with the region of infarction and are
7 days after the stroke and persists for several months. indicative of permanent neuronal death. Mismatched
544 Section III  Problem Solving: Disease Categories

A B

Figure 16-18 Multiple cortical infarcts in

a newborn with atrioventricular septal defect.
DWI (A and B) and ADC (C and D) demon-
strate multiple cortical areas with reduced dif- C D
fusion and decreased ADC values.

A B
Figure 16-19 Superior sagittal sinus thrombosis in a newborn with sepsis. Coronal T1 (433/9) shows abnormal increased signal in the supe-
rior sagittal sinus (arrow) and MR venography without contrast demonstrates lack of flow (arrows).
 Chapter 16 Neuroimaging of Pediatric Hypoxic–Ischemic Injury 545

diffusion and perfusion abnormalities with the perfu- Suggested Readings

SECTION III
sion abnormality larger than the diffusion abnormal- Auld KL, Ashwal S, Holshouser BA, et al. Proton magnetic resonance
ity may be indicative of a region of reversible ischemic spectroscopy in children with acute central nervous system injury. Pediatr
penumbra. Neurol. 1995;12:323-334.
Barkovich AJ. Techniques and methods in pediatric magnetic resonance
imaging. Semin Ultrasound CT MR. 1988;9:186-191.
Magnetic Resonance Angiography in Ischemic Barkovich AJ. The encephalopathic neonate: choosing the proper imaging
Stroke During Infancy and Childhood technique. AJNR Am J Neuroradiol. 1997;18:1816-1820.
Barkovich AJ. Pediatric Neuroradiology. 4th ed. Philadelphia: Lippincott
Magnetic resonance angiography is useful in cases of Williams & Wilkins; 2005.
thrombosis to localize the site of occlusion and for cases Barkovich AJ. MR imaging of the neonatal brain. Neuroimaging Clin N Am.
2006;16:117-135:viii-ix.
of severe underlying vasculopathy. Barkovich AJ, Sargent SK. Profound asphyxia in the premature infant: imaging
findings. AJNR Am J Neuroradiol. 1995;16:1837-1846.
Venous Thrombosis During Infancy Barkovich AJ, Truwit CL. Brain damage from perinatal asphyxia: correlation
of MR findings with gestational age. AJNR Am J Neuroradiol. 1990;11:1087-
and Childhood 1096.
Pediatric patients frequently present to the hospital with Barkovich AJ, Good WV, Koch TK, Berg BO. Mitochondrial disorders: analysis
dehydration, which is a major risk factor of intracranial of their clinical and imaging characteristics. AJNR Am J Neuroradiol.
1993;14:1119-1137.
venous thrombosis. Other ­hypercoagulable states that Barkovich AJ, Westmark K, Partridge C, Sola A, Ferriero DM. Perinatal asphyxia:
may cause venous thrombosis include factor V Leiden, MR findings in the first 10 days. AJNR Am J Neuroradiol. 1995;16:427-438.
Barkovich AJ, Westmark KD, Bedi HS, Partridge JC, Ferriero DM, Vigneron
protein C, protein S, anticardiolipin antibody, polycy- DB. Proton spectroscopy and diffusion imaging on the first day of life
themia, sepsis, tumor, trauma, disseminated intravascu- after perinatal asphyxia: preliminary report. AJNR Am J Neuroradiol.
lar coagulation, and metabolic disorders. 2001;22:1786-1794.
Bartha AI, Yap KR, Miller SP, et al. The normal neonatal brain: MR imaging,
diffusion tensor imaging, and 3D MR spectroscopy in healthy term
Cranial US in Venous Thrombosis During Infancy neonates. AJNR Am J Neuroradiol. 2007;28:1015-1021.
and Childhood Cady EB, Penrice J, Amess PN, et al. Lactate, N-acetylaspartate, choline and
creatine concentrations, and spin-spin relaxation in thalamic and occipito-
Color Doppler US of the superior sagittal sinus should parietal regions of developing human brain. Magn Reson Med. 1996;36:878-
always be obtained as part of the cranial US in neonate 886.
Copen WA, Schwamm LH, Gonzalez RG, et al. Ischemic stroke: effects of
infants. Although, color Doppler cannot rule out venous etiology and patient age on the time course of the core apparent diffusion
thrombosis in other venous sinuses, it is a simple and coefficient. Radiology. 2001;221:27-34.
inexpensive way to detect thrombosis of the superior Detre JA, Wang ZY, Bogdan AR, et al. Regional variation in brain lactate in
Leigh syndrome by localized 1H magnetic resonance spectroscopy. Ann
sagittal sinus that could be unnoticed on routine gray- Neurol. 1991;29:218-221.
scale cranial US. Enzmann D, Murphy-Irwin K, Stevenson D, Ariagno R, Barton J, Sunshine P.
The natural history of subependymal germinal matrix hemorrhage. Am J
Perinatol. 1985;2:123-133.
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2000;21:1490-1496.
Hyperattenuation in the venous sinus or in the cortical Frigieri G, Guidi B, Costa Zaccarelli S, et al. Multicystic encephalomalacia in
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rial distribution. CT venography demonstrates a filling leukomalacia: diagnosis by real time ultrasound and correlation with
autopsy findings. Pediatrics. 1982;69:282-284.
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Riikonen R, Santavuori P. Hereditary and acquired risk factors for childhood Steinman KJ, Gorno-Tempini ML, Glidden DV, et al. Neonatal watershed brain
stroke. Neuropediatrics. 1994;25:227-233. injury on magnetic resonance imaging correlates with verbal IQ at 4 years.
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Neuroradiol. 1999;20:1658-1670. perinatal hypoxic-ischemic encephalopathy with ulegyria. Epilepsy Res.
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infarction. Pediatrics. 2008;122:e46-e52. edited MR spectroscopy in premature neonates with and without pentobarbital
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Lafeber HN, Valk J. Early MR features of hypoxic-ischemic brain injury Williams LS, Garg BP, Cohen M, Fleck JD, Biller J. Subtypes of ischemic stroke
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 chapter 17

Intrauterine and Perinatal

­Infections
Andre D. Furtado, Saulo Lacerda, and Thomas P. Naidich

IMAGING: WHY, WHO, AND HOW? GENERAL CONSIDERATIONS

Why Imaging? Perinatal infections are most commonly caused by agents
Perinatal infections are a group of infections caused included in the acronyms TORCH (Toxoplasmosis, Oth-
by bacteria, viruses, or parasites that are transmitted ers, which is mainly syphilis, Rubella, Cytomegalovirus,
from a mother to her baby during pregnancy or child- Herpes simplex) and HIV (human immunodeficiency
birth. Brain damage is the most serious complication. virus). Bacterial infections are most commonly trans-
Imaging provides important diagnostic and prognostic mitted from the cervix during delivery, whereas toxo-
information. plasmosis, syphilis, rubella, CMV, and most viruses
are transmitted via the placenta. Herpes simplex virus
Who Needs Imaging? (HSV) infection with active vaginal vesicles and HIV can
also be transmitted during delivery. In such cases, cesar-
Imaging should be performed in all patients with sus- ean section should be performed.
pected perinatal infection. Clinical presentation includes The most common imaging findings in infected
fever, maculopapular rash, hepatosplenomegaly, micro- fetuses include abnormal amniotic fluid volume, fetal
cephaly, seizures, jaundice, thrombocytopenia, and gen- growth restriction, hyperechogenic bowel, ascites, intra-
eralized lymphadenopathy. hepatic or intracranial calcifications, and ventricular
dilatation. Ventricular dilatation may be secondary to
How to Image/Which Imaging? malformation or brain damage. White matter injury on
prenatal brain MRI has been associated with increased
Cerebral US is usually performed as the first imag- risk of premature birth.
ing modality. Monthly obstetric ultrasound may be
performed to evaluate brain abnormalities, calcifi-
COMMON IMAGING FINDINGS
cations, and growth retardation. Postnatally, US can
be as good as computed tomography (CT) to detect
Ventriculomegaly
intracranial calcifications with the advantages of no
radiation use, cost effectiveness, and less stress for the Although ventriculomegaly is one of the most common
neonate. US may demonstrate echogenic vasculature imaging findings in fetuses with intrauterine infection,
in the basal ­ganglia of neonates with cytomegalovi- only approximately 5% of cases of fetal ventriculo-
rus (CMV), rubella, or congenital syphilis infections, megaly can be attributed to intrauterine infection. Most
but this finding is not specific and may also be seen cases are attributed to neural tube defects.
in cases of chromosomal abnormality, such as trisomy Two criteria for fetal ventriculomegaly have been
13 ­syndrome. proposed: the lateral ventricular width and the lateral
CT scanning is a useful modality for investigating ventriculo-hemispheric ratio (VR).
calcification in patients with neonatal infections. Dur- The lateral ventricular width is measured at the
ing the perinatal period, CT should be performed with a atrium of the lateral ventricles using the choroid plexus
low-dose protocol. as a landmark. This measurement typically ranges from
Magnetic resonance imaging (MRI) is the modality 4 to 8 mm from 15 weeks to term. An upper limit of
of choice for evaluating the fetal brain providing diag- 10-12 mm is most commonly used (Figure 17-1). It is a
nostic and prognostic information in neonates with very useful criterion during the second trimester.
neonatal infection. Sedation of the mother is especially VR is the distance from the midline to the lateral ven-
important for fetuses younger than 28 weeks of gesta- tricular wall divided by the distance from the midline to
tional age, when the head is not yet engaged in the pel- the inner table of the parietal bone on the same image.
vis and moves considerably. This ratio is usually constant from 24 weeks to term, with

547
548 Section III  Problem Solving: Disease Categories

Figure 17-1 Ventriculomegaly. Axial T2-weighted HASTE Figure 17-2 Calcifications. Axial reformatted three-dimensional spoiled
(1000/144) image of a fetus at 30 weeks of gestation demonstrating gradient-recalled T1-weighted (1940/2) image of a 3-month-old boy with
enlarged lateral ventricles measured at the level of the atria (>10 mm). congenital toxoplasmosis demonstrating multiple foci of high signal (arrow-
heads) suggestive of calcifications. Also note a few cyst lesions (arrows).

an upper limit of 50%, but is normally much higher dur-

ing early pregnancy and variable from 15 to 24 weeks.

Intracranial Calcifications
Intracranial calcifications are typically small and often
do not exhibit the acoustic shadowing on cranial US.
CT is considered the best imaging modality for detecting
and characterizing intracranial calcifications. On MRI,
calcifications usually present low T2 signal but variable
T1 signal (low, intermediate, high, and mixed signal
intensity) (Figure 17-2).
Intracranial calcifications may be difficult to detect,
particularly during the second trimester and are most
frequently seen in cases of fetal CMV and toxoplasmosis
infections, but have been reported with congenital vari-
cella, HSV, and rubella.

Hydranencephaly
Hydranencephaly is considered the most severe manifes-
tation of the brain damage. The cerebral hemispheres are
almost entirely replaced by fluid, but the brainstem, thal-
ami, and posterior fossa structures are usually preserved. Figure 17-3 Hydranencephaly. Axial T2-weighted (4300/102.7)
image demonstrating of no discernible brain parenchyma, which is
US demonstrates fluid-filled intracranial cavity with no replaced by cerebrospinal fluid–filled sac spaces (asterisk). The thalami
discernible cerebral hemispheres. The falx is typically pres- typically are preserved (arrows).
ent but in some cases it may be absent. Hydranencephaly
is more common in cases of congenital HSV infection and
unusual in cases of toxoplasmosis and CMV (Figure 17-3). infections. There are several measurements to assess
microcephaly such as biparietal diameter, head circum-
Microcephaly ference, abnormal head circumference to abdominal cir-
cumference, head circumference to femur length ratios,
Microcephaly (small head size) is a result of poor cere- and poor fetal head growth on serial examinations.
bral development or arrested cerebral growth. It is often Head circumference of 2 standard deviations below the
associated with chromossomal syndromes, fetal alco- mean for gestational age is considered ­microcephaly.
hol syndrome, cerebral malformations, and congenital Isolated microcephaly has been documented in cases of
 Chapter 17 Intrauterine and Perinatal Infections 549

congenital CMV, HSV, and rubella virus. It is less com- tent pregnant women are mild. Cats are the definitive

SECTION III
mon in cases of congenital toxoplasmosis infection. hosts and the three principal ways of transmission are
ingestion of inadequately cooked infected meat, inges-
tion from contaminated soil or water, or transplacental.
DIFFERENTIAL DIAGNOSTIC
Congenital toxoplasmosis infection typically causes
The differential diagnostic of congenital infection includes meningoencephalitis, which may result in hydrocephalus,
fetal alcohol syndrome, teratogens, tuberous sclerosis, microcephaly, calcifications, porencephaly, or hydranen-
venous malformation, arteriovenous fistula, chronic cephaly. Congenital toxoplasmosis may not be apparent
venous ischemia, post natal neurocysticercosis, Fahr dis- until late in infancy. The prognosis for normal neurologic
ease, idiopathic familial basal ganglia calcifications, and outcome is good in the absence of brain abnormalities.
pseudo-TORCH syndromes, such as Baraister-Reardon,
Aicardi-Goutieres, progressive cerebral and cerebellar Cranial Ultrasound
demyelination. Metabolic disorders should always be Nonshadowing intracranial are the most typical imag-
ruled out, because early diagnosis and treatment of meta- ing finding, which may be periventricular or random in
bolic disorders can prevent further brain damage. ­distribution. US may miss small calcifications. ­Intrauterine
Overviews of the most common intrauterine and growth restriction and ventriculomegaly can also occur.
perinatal infections are discussed separately. Echogenic bowel, hydramnios, enlarged placenta, hepa-
tosplenomegaly, ascites, and fetal may be present.
Cytomegalovirus Other less specific imaging findings are subependy-
mal or white matter cysts, and echogenic striothalamic
CMV is considered the most common serious congenital arteries (“candlestick sign”).
infection in the United States, affecting approximately
40,000 newborns each year. Most infants exposed to Computed Tomography
CMV before birth develop normally and do not show CT demonstrates periventricular or random intracere-
any symptoms; however, as many as 6,000 are born with bral calcifications, ocular calcifications, hydrocephaly,
serious complications. CMV infection in the newborn is and microcephaly (Figure 17-6). The ocular calcifica-
usually diagnosed by urine culture. Treatment is basi- tions may be similar to retinoblastoma.
cally supportive; however, ganciclovir and foscarnet may
have some utility in selected cases. Magnetic Resonance Imaging
The brain is the most commonly affected organ. MRI is routinely utilized to assess brain lesions, even
Congenital CMV infection has been associated with when the US exam is normal. MRI may also be used
microcephaly, cerebral calcifications, lissencephaly, serially during pregnancy for detection of development
polymicrogyria, cerebellar hypoplasia, dysplastic white of brain abnormalities. In the acute phase, the white
matter, porencephaly, and ventricular dilatation. matter abnormality may manifest as effacement of the
intermediate zone layer. Leukomalacia with parenchy-
Cranial Ultrasound mal calcifications and cortical malformations occur later
Cranial US can demonstrate calcifications, which are (Figure 17-7). The typically imaging finding is cystic
usually periventricular, ventriculomegaly, and micro- lesions with calcified nodules (Figure 17-8).
cephaly. Other findings that may be seen on US include
intrauterine growth restriction, hepatosplenomegaly, Congenital Syphilis
cardiomyopathy, echogenic bowel, and hydrops.
Syphilis can also be transmitted from the mother to
Computed Tomography the fetus before birth. It is estimated that up to 50%
CT is a valuable modality for detecting and character- of infants born with syphilis are premature, stillborn,
izing diminutive periventricular and subependymal or die shortly after birth. Symptoms of syphilis may
calcifications. CT can also show ventriculomegaly and develop as late as 2 years of age. Hepatosplenomegaly is
microcephaly. a very sensitive sign but is nonspecific.
Leptomeningeal enhancement, particularly involv-
Magnetic Resonance Imaging ing the basal meninges and extending into the brain
MRI is excellent for evaluating white matter volume loss parenchyma via the Virchow-Robin spaces may result in
with subsequent enlargement of lateral ventricles (Fig- enhancing intraparenchymal lesions, known as gumma.
ures 17-4 and 17-5). MRI may also shows enlargement Neonates with congenital syphilis may develop syphi-
of the subarachnoid spaces, focal areas of dysplastic litic endarteritis, which can cause ischemic or hem-
cortex, delayed myelination, paraventricular cysts, and orrhagic strokes predominantly involving unilateral
some intracerebral calcification. MRI is not sensitivity periventricular white matter.
for diminutive calcifications.
Congenital Rubella (German
Toxoplasmosis Measles)
It is estimated that 400 to 4,000 cases of congenital Rubella is extremely rare because of vaccination and pre-
toxoplasmosis occur per year in the United States. Most natal screening. Rubella is the virus that causes German
cases of acquired Toxoplasma gondii in immunocompe- measles. When rubella infection occurs during early
550 Section III  Problem Solving: Disease Categories

A B

C D
Figure 17-4 Congenital cytomegalovirus infection in a 15-year-old boy. Axial T2 (4700/111.6), gradient-echo (650/25), and sagittal T1 (350/9)
images demonstrating dysplastic white matter (curved arrows), periventricular calcifications (arrowheads), and multiple areas of cortical malforma-
tions (arrows), most commonly polymicrogyria.

pregnancy, it can be transmitted to the fetus, resulting after maternal varicella during the first two trimesters is
in serious birth defects, including heart abnormalities, less than 1%.
mental retardation, blindness, and deafness. Imaging Intrahepatic and intracranial calcifications are the
demonstrates nonspecific findings such as microceph- most common imaging findings. Although rare, intra-
aly, leukoencephalopathy, and calcifications, particu- uterine encephalitis with atrophy and porencephaly
larly in the basal ganglia. have been reported. Calcifications may be seen in
many organs, such as liver, heart, and kidney. Polyhy-
Congenital Varicella dramnios due to neurologic impairment of swallow-
ing, limb hypoplasia, and diaphragmatic paralysis are
Transplacental transmission of varicella following other imaging findings. Autonomic nervous system
maternal chickenpox infection carries low risk of birth dysfunction may cause neurogenic bladder, hydroure-
defects. The incidence of congenital varicella syndrome ter, esophageal dilatation with aspiration pneumonia.
 Chapter 17 Intrauterine and Perinatal Infections 551

SECTION III
A B C

D E F
Figure 17-5 Congenital cytomegalovirus (CMV) infection in a 6-month-old girl. Axial T2 (2460.2/110) (A, B, E), T2 FLAIR (11000/140) (C, F),
and sagittal T1 (406/12) (D) images demonstrating dysplastic white matter (arrows) with periventricular cysts (arrowheads) and multiple areas of
cortical malformations, polymicrogyria (curved arrows).

Cutaneous lesions in dermatomal distribution may hydrocephalus. Brain imaging findings in fetus and neo-
also be seen. nates with congenital LCMV infection may be similar
to those of toxoplasmosis and CMV. Of note, hepato-
Lymphocytic Choriomeningitis splenomegaly is infrequent in LCMV but is very com-
mon in toxoplasmosis and CMV.
Virus
Lymphocytic choriomeningitis virus (LCMV) usually Parvovirus B19
infects wild mice, but humans and a few other animals
can also be infected. The virus is not transmitted from Parvovirus B19 infection during pregnancy can result in
person to person; however, transplacental transmission adverse fetal outcome. The risk of congenital defects is
may occur. For most healthy people, the disease is mild increased if maternal infection occurs during the first two
and recovery is complete. LCMV infection can have seri- trimesters, but may also occur during the third trimester.
ous consequences in pregnant women and immuno- Infection during pregnancy can cause severe fetal anemia
suppressed individuals. and nonimmune hydrops fetalis, myocarditis, and car-
Congenital LCMV infection can result in miscar- diac failure. Serial middle cerebral artery peak systolic flow
riage or birth defects, including severe brain damage. velocity evaluation may be used to predict severe fetal ane-
Therefore, pregnant women should avoid contact with mia and guide the treatment with cordocentesis transfu-
rodents, including pet hamsters. sion. Parvovirus infected fetuses with severe anemia treated
LCMV causes chorioretinitis, ependymitis, ependy- with multiple cordocentesis transfusions may develop
mal calcifications, polymicrogyria, microcephaly, and polymicrogyria, heterotopia, or cerebellar hemorrhage.
552 Section III  Problem Solving: Disease Categories

A B
Figure 17-6 Axial noncontrast computed tomography showing dysplastic white matter bilaterally with secondary dilatation of the ventricles
(arrows). A normal third ventricle (arrowheads) helps to rule out acute hydrocephalus in this group of patients.

West Nile Virus Toxoplasmosis, CMV, and progressive multifocal leu-

koencephalomalacia caused by JC virus are the most
Population studies have not demonstrated that infants common opportunistic infections in children with AIDS
who were exposed to West Nile virus in utero have a and low CD4 cell count.
higher risk of major birth defects. Rare anecdotal cases
of cortical malformations, such as microcephaly and Intrauterine and Perinatal HSV
lissencephaly, or cystic white matter changes have been
Type 2 Infections
reported.
HSV Type 2 infection can also be transmitted in utero
INTRAUTERINE AND PERINATAL or during birth. Pregnant women with genital herpes
INFECTION are at high risk for miscarriage or delivering a low-
birthweight baby. Infection can be passed to the infant
Intrauterine and Perinatal HIV at the time of delivery if active genial herpes lesions are
Infection present. Diagnosis can be made via viral culture or poly-
merase chain reaction. HSV Type 2 infection early in
HIV infection can be transmitted in utero or during birth. pregnancy can cause hydranencephaly, intracranial cal-
Without treatment, the transmission rate of pregnant cifications, and microphthalmia. If the infection occurs
women infected with HIV to infect their newborn infants late in pregnancy or during delivery, white matter and
is approximately 30%. With treatment, it is possible to cortical involvement may rapidly affect the whole brain.
decrease the transmission rate to less than 2%. Elective There are often multiple hemorrhagic foci, cortical or
cesarean section can prevent vertical transmission. leptomeningeal enhancement, and restricted diffusion.
Congenital HIV infection rarely manifests acute neo- HSV-2 encephalitis usually develops in 5 to 15 days after
natal symptoms. It most commonly causes developmen- birth. Later development of areas of cystic white matter
tal delay. The most common imaging findings are brain changes is common.
atrophy and basal ganglia calcifications. Neck lymph-
adenopathy and benign lymphoepithelial cysts in the NEONATAL INFECTION
parotid glands may also be seen.
With highly active antiretroviral therapy, patients Bacterial Infection
with HIV live longer and HIV-related encephalopathy
is becoming more common. Children with acquired Pregnant women with vaginitis or urinary tract infection
immunodeficiency syndrome (AIDS) may develop cere- caused by Group B streptococcus can infect their infants
bral aneurysms, central nervous system lymphoma, or in utero or during delivery. Group B streptococcus can
extraaxial leiomyoma or leiomyosarcoma. HIV myelop- cause premature birth, neonatal pneumonia, and neo-
athy with corticospinal tract degeneration and preser- natal meningitis. Other less common causes of neona-
vation of the posterior columns is not uncommon in tal bacterial meningitis are Escherichia coli, Streptococcus
children with AIDS. pneumoniae, Haemophilus influenzae type B, and Listeria
 Chapter 17 Intrauterine and Perinatal Infections 553

SECTION III
A B

C D
Figure 17-7 Congenital toxoplasmosis in a 21-year-old patient. Axial noncontrast computed tomography, T2 (5000/107.7), and gradient-echo
(717/25) images showing marked dilatation of the ventricles in part due to dysplastic white matter (curved arrows). Note there is also a component
of hydrocephalus with dilatation of the temporal horns of the lateral ventricles and third ventricle (asterisk). A pattern of multiple random calci-
fications is frequently seen in severe cases of congenital toxoplasmosis (arrows).

monocytogenes. The most common imaging finding in has been reported in a neonate with Citrobacter koseri
neonatal meningitis is hydrocephalus, which occurs late meningitis. Citrobacter meningitis usually carries poor
in the course of the disease. Imaging should always be neurologic outcome, with seizures, mental retardation,
performed in patients with bacterial meningitis if they and paresis.
do not have a rapid response to treatment or develop
focal neurologic deficit. In such patients, imaging is very Fungal Infection
helpful in investigating for occlusive venous thrombosis,
arterial infarcts, cerebritis, empyema, and brain abscess. Candida
Although neonatal Citrobacter koseri (diversus) men- Candida as a commensal fungus is frequent in the intes-
ingitis is rare, it is often complicated by the formation tine and other locations in neonates. Most infections
of brain abscesses, which seem to have a predilection do not occur by maternal infection. Vaginal infection
for the frontal lobes. Diffuse neonatal pneumocephalus is not an indication for cesarean section. The key risk
554 Section III  Problem Solving: Disease Categories

Cardoza JD, Filly RA, Podrasky AE. The dangling choroid plexus: a sonographic
observation of value in excluding ventriculomegaly. AJR Am J Roentgenol.
1988;151:767-770.
Chervenak FA, Jeanty P, Cantraine F, et al. The diagnosis of fetal microcephaly.
Am J Obstet Gynecol. 1984;149:512-517.
Coakley FV, Glenn OA, Qayyum A, Barkovich AJ, Goldstein R, Filly RA,
Fetal MRI: a developing technique for the developing patient. AJR Am J
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Collins AT, Cromwell LD. Computed tomography in the evaluation of
congenital cerebral toxoplasmosis. J Comput Assist Tomogr. 1980;4:326-329.
Crino JP. Ultrasound and fetal diagnosis of perinatal infection. Clin Obstet
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Dubrovsky T, Curless R, Scott G, et al. Cerebral aneurysmal arteriopathy in
childhood AIDS. Neurology. 1998;51:560-565.
Elective caesarean-section versus vaginal delivery in prevention of vertical
HIV-1 transmission. a randomised clinical trial. The European Mode of
Delivery Collaboration. Lancet. 1999;353:1035-1039.
Fakhry J, Khoury A. Fetal intracranial calcifications. The importance of
periventricular hyperechoic foci without shadowing. J Ultrasound Med.
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Filippi L, Serafini L, Dani C, et al. Congenital syphilis: unique clinical
presentation in three preterm newborns. J Perinat Med. 2004;32:90-94.
Gavin P, Yogev R. Central nervous system abnormalities in pediatric human
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with West Nile virus during pregnancy. MMWR Morb Mortal Wkly Rep.
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Lago EG, Baldisserotto M, Hoefel Filho JR, Santiago D, Jungblut R. Agreement
Figure 17-8 Congenital toxoplasmosis. Axial T2-weighted HASTE between ultrasonography and computed tomography in detecting
(1000/144) image of a fetus at 34 weeks of gestation demonstrating intracranial calcifications in congenital toxoplasmosis. Clin Radiol.
cyst lesions, some with calcified nodules (arrows) and solid nodules in 2007;62:1004-1011:Epub 2007 Jul 1020.
the cerebral parenchyma. Lai PH, Lin SM, Pan HB, Yang CF. Disseminated miliary cerebral candidiasis.
AJNR Am J Neuroradiol. 1997;18:1303-1306.
Leung AK, Sauve RS, Davies HD. Congenital cytomegalovirus infection. J Natl
Med Assoc. 2003;95:213-218.
Marques Dias MJ, Harmant-van Rijckevorsel G, Landrieu P, Lyon G. Prenatal
factors are catheters and antibiotics. Candida infection cytomegalovirus disease and cerebral microgyria: evidence for perfusion
can cause meningitis, multiple enhancing hemorrhagic failure, not disturbance of histogenesis, as the major cause of fetal
cytomegalovirus encephalopathy. Neuropediatrics. 1984;15:18-24.
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Nyberg Da MBSPDH. Cerebral malformations. Diagnostic Ultrasound of Fetal
Suggested Readings Anomalies: Text and Atlas. Chicago, IL: Year Book Medical Publishers; 1990,
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Alviedo JN, Sood BG, Aranda JV, Becker C. Diffuse pneumocephalus in O’Leary DR, Kuhn S, Kniss KL, et al. Birth outcomes following West Nile Virus
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 chapter 18

Head and Neck Radiology

Girish M. Fatterpekar and Peter M. Som

This chapter on head and neck radiology follows a with the third gestational week. Mondini anomaly refers
slightly different format than the rest of the textbook. to incomplete partition of the cochlea resulting in 11⁄2
Instead of a problem-solving approach, a case-based turns instead of the normal 21⁄2 to 23⁄4 turns and rep-
approach is used. Toward this end, the discussion in this resents arrest correlating with the seventh gestational
chapter is divided into seven subsections. Each subsec- week. Most patients present with congenital sensorineu-
tion deals with a particular part of the head and neck: ral hearing loss. Characteristic radiologic findings are
temporal bone; orbit; sinonasal cavities; salivary glands; variable depending on the gestational age at arrest of
masticator space, oral cavity including floor of mouth, the developing otocyst. Thus, radiologic manifestations
and pharynx; thyroid, larynx; and other regions of the include complete labyrinthine aplasia, common cavity,
neck. In each of these subsections, the most common, incomplete partition of the cochlea, and various other
clinically important cases are discussed. In a few of dysplasias involving the cochlea, vestibule, and semi-
the pathologies outlined, the discussion is boosted by circular canals (Figure 18-2). Different classification
including relevant images of the differential diagnosis, systems have been proposed based on the anomalies
allowing illustration of key distinguishing features. seen. However, it is best to describe the anomalies with-
out delving much into the classification system because
TEMPORAL BONE of the lack of consensus on any one of them. Of note,
in some inner ear anomalies, such as Alexander and
Eleven cases are discussed in this section. They include Scheibe aplasia, the membranous labyrinth including
congenital anomalies involving the external ear, middle the organ of Corti are affected. Radiologic assessment
ear and inner ear, including large vestibular aqueduct for such membranous abnormalities is beyond the reso-
syndrome, trauma (e.g., fractures), vascular anomalies lution of current imaging modalities.
(e.g., aberrant carotid artery), infectious and inflamma-
tory conditions (e.g., mastoiditis, cholesteatoma, Bell’s Large Vestibular Aqueduct
palsy), and tumors (e.g., cholesterol granuloma, glomus
Syndrome
tumor, acoustic schwannoma).
Large vestibular aqueduct syndrome results from
Congenital External and Middle Ear abnormal congenital enlargement of the membranous
Anomalies endolymphatic duct and sac. Most patients present
with congenital sensorineural hearing loss. Character-
Anomalies of the external and middle ear usually occur istic radiologic findings include an enlarged vestibular
together due to the common embryologic origin from aqueduct (>1.5 mm in diameter) in its midportion. A
the first and second branchial arches. Isolated anoma- simpler way to diagnose this entity is to correlate the
lies occur occasionally. An atretic pinna and hearing caliber of the vestibular aqueduct to the adjacent poste-
loss are common presenting features. Characteristic rior semicircular canal. The posterior semicircular canal
radiologic features include an atretic, ectopically placed is approximately 1.5 mm in diameter. Thus, a vestibular
pinna, absent or hypoplastic external auditory canal, aqueduct caliber greater than that of the adjacent pos-
hypoplastic tympanic cavity, and malformed ossicles, terior semicircular canal is suggestive of large vestibular
which are frequently attached to the lateral attic wall aqueduct syndrome (Figure 18-3).
(Figure 18-1). Associated radiologic features can include
an anomalous course of the facial nerve as it traverses Temporal Bone Trauma
the tympanic cavity and inner ear anomalies.
Temporal bone fractures usually occur secondary to
Congenital Inner Ear Anomalies blunt trauma. Three kinds of temporal bone fractures
are known based on their orientation to the long axis of
Anomalies of the inner ear result from partial or com- the temporal bone: longitudinal variety, with the fracture
plete failure of development of the otic cyst during the line along the long axis of the temporal bone; transverse
first few weeks of embryonic life. Michel and Mondini variety, with the fracture line perpendicular to the long
malformations are some of the more common inner axis of the temporal bone; and mixed variety, which is a
ear anomalies seen. Michel deformity refers to complete combination of the two fractures. The longitudinal vari-
labyrinthine aplasia and represents arrest ­correlating ety causes disruption of the ossicles and trauma to the

557
558 Section IV Problem Solving: Anatomic Regions

facial nerve. The transverse variety is more often asso-

ciated with fractures of the inner ear structures. Swell-
ing and tenderness to the ear following temporal bone
trauma are common clinical features. Depending on
the underlying structures affected, patients can present
with conductive or sensorineural hearing loss and facial
paresis or paralysis. A characteristic radiologic feature
is demonstration of linear nonserrated lucencies con-
A sistent with fractures traversing the temporal bone. The
course of the fracture line should be carefully evaluated
to assess for fractures involving the ossicles and their
associated dislocation, for fractures involving the inner
ear structures, which can result in perilymph fistula, and
for fractures involving the tegmen tympani, which can
result in cerebrospinal fluid otorrhea. Hemotympanum
as suggested by opacification of the mastoid air cells is
a common associated finding (Figure 18-4). Very rarely,
laceration of the adjacent venous sinus, such as the sig-
B moid sinus, is seen. Cerebrospinal fluid otorrhea or rhi-
norrhea and meningitis are delayed complications of
temporal bone trauma.

Aberrant Carotid Artery

Aberrant carotid artery represents an enlarged infe-
rior tympanic artery anastomosing with an enlarged
caroticotympanic artery, when the vertical portion of
C the petrous segment of the internal carotid artery is
underdeveloped or regresses during embryogenesis. It is
Figure 18-1 A: High-resolution axial computed tomographic essential to recognize this entity and not mistake it for a
(CT) scan through the temporal bones demonstrating a dysplastic “mass” so as to avoid biopsy, which can otherwise result
left pinna and an absent external auditory canal. B: High-resolu-
tion coronal reformatted CT scan demonstrating a hypoplastic left in catastrophic hemorrhage. Most patients are asymp-
tympanic cavity and malformed ossicles attached to the lateral tym- tomatic. Pulsatile tinnitus and conductive hearing loss
panic cavity. C: In a different patient, axial CT scan demonstrating are symptoms that have otherwise been described. Char-
malformed ossicles on the left side and a hypoplastic tympanic cav- acteristic radiologic findings include an absent normal
ity. On the right side, the anomaly is more subtle. The ice-cream
cone appearance of the ossicles (produced by the head of the mal-
vertical petrous portion of the carotid canal. Instead, the
leus and body of incus) is normally seen. However, close observa- carotid artery is seen to course upward and slightly later-
tion reveals that the ossicles are attached to the lateral wall of the ally through an enlarged inferior tympanic canaliculus.
tympanic cavity. It protrudes variably into the tympanic cavity, posi-
tioned lateral to the promontory of the middle ear, and

A B
Figure 18-2 A: Axial computed tomographic (CT) scan demonstrating congenital cystic dilatation of the cochlea (arrowhead) with incomplete
partitioning. B: In a different patient, high-resolution coronal CT scan demonstrating a dilated dysplastic vestibule (arrowhead) and lateral semi-
circular canal (arrow). There is mild dysplasia of the basal turn of cochlea (curved arrow).
 Chapter 18 Head and Neck Radiology 559

SECTION IV
A

Figure 18-3 Axial computed tomographic scan demonstrating

enlarged caliber (> 1.5 mm) of the vestibular aqueduct (star). Arrow
points to posterior semicircular canal whose caliber can be used as B
a rough reference guide to determine the presence or absence of an
enlarged vestibular aqueduct. A vestibular aqueduct caliber greater
than that of the posterior semicircular canal is suggestive of large ves-
tibular aqueduct syndrome.

C
Figure 18-5 A: Axial computed tomographic scan demonstrating
a curvilinear structure coursing through the medial wall of the right
tympanic cavity, which appears contiguous with the vertical portion
of the petrous internal carotid artery (ICA) posteriorly and with the
horizontal portion of the petrous ICA anteriorly. B: Coronal reformat-
ted CT scan demonstrating the same lesion to be in close proximity
to the cochlear promontory. C: More posteriorly in the coronal plane,
this lesion is contiguous with the vertical segment of the petrous ICA.
The diagnosis is aberrant carotid artery.

However, if not controlled, secondary complications

Figure 18-4 Axial computed tomographic scan demonstrating can occur. Most patients present with fever and otalgia
a transverse fracture (arrowheads) extending through the inner ear
involving the posterior semicircular canal (curved arrow) and the ves-
following a bout of upper respiratory tract infection.
tibule (arrow). Opacified tympanic cavity and mastoid air cells reflect Imaging in acute otitis media is not routinely obtained.
hemotympanum. However, in patients who do not respond to antibiotic
treatment or in whom complications are suspected,
contrast-enhanced computed tomographic (CT) scans
courses further anteriorly through a normal horizontal or magnetic resonance imaging (MRI) studies can be
petrous portion of the carotid canal (Figure 18-5). Dif- obtained. Typically, opacified mastoid air cells and tym-
ferential diagnosis includes glomus tympanicum and panic cavity will be seen. Destruction of the mastoid air
persistent stapedial artery. Glomus tympanicum will be septae is suggestive of coalescent mastoiditis. Erosion of
seen as a focal, intensely enhancing lesion overlying the the cortex and extension of the infection into the adja-
cochlear promontory. Persistent stapedial artery will be cent soft tissues or intracranial compartment can result
seen as a curvilinear enhancing structure coursing along in abscess formation (Figure 18-6). Labyrinthitis, otitic
the medial wall of the tympanic cavity, with an absent hydrocephalus, venous sinus thrombosis, venous infarc-
foramen spinosum on the ipsilateral side. tion, and meningitis are other complications that can
be seen.
Acute Mastoiditis
Cholesteatoma
Acute otitis media is seen most often in the pediatric
population. It refers to inflammation of the middle ear Cholesteatoma is a collection of keratinous debris seen
and mastoid air cells with resultant fluid collections. In typically within the tympanic cavity. Such a collec-
most patients, the condition resolves with antibiotics. tion commonly occurs following ingrowth of stratified
560 Section IV Problem Solving: Anatomic Regions

s­ quamous epithelium from the external auditory canal the imaging modality of choice to evaluate of cholestea-
into the tympanic cavity, secondary to external otitis and toma. It demonstrates a nonenhancing soft tissue lesion
perforation of the ear drum. Less commonly, such collec- within the tympanic cavity with characteristic erosion of
tions develop from congenital rests. Most patients pres- scutum and ossicles. Widening of the Prussak space will
ent with painless otorrhea and hearing loss. CT scan is also be seen (Figure 18-7). Less commonly, erosion of
the otic capsule is seen, resulting in perilymph fistula.
Differential diagnosis includes glomus tympanicum
and granulation tissue within tympanic cavity. Glomus
tympanicum will be seen as a focal enhancing soft tis-
sue mass overlying the cochlear promontory. There is no
erosion of the adjacent ossicles or otic capsule. Granula-
tion tissue will be seen as an enhancing soft tissue mass
A within the tympanic cavity. No erosion of the ossicles or
scutum or otic capsule will be seen.

Bell’s palsy
Bell’s palsy is an acute, idiopathic, unilateral, peripheral,
lower motor neuron facial nerve paralysis that gradually
resolves over time. Most patients present with an acute
onset of facial weakness. MR is the imaging modality
of choice. The typical imaging appearance is asymmet-
ric enhancement of some segments of the facial nerve
B or of the entire course of the facial nerve as it traverses
the temporal bone (Figure 18-8). No obvious thicken-
Figure 18-6 A: Axial computed tomographic (CT) scan demon- ing of the facial nerve is seen. Differential diagnosis
strating opacified right mastoid air cells and tympanic cavity. There includes perineural extension of the tumor and facial
is a suggestion of destruction of mastoid cortex (arrowhead). B: Axial nerve schwannoma. Usually with perineural extension,
CT scan, soft tissue window demonstrating soft tissue swelling (star)
suggestive of phlegmonous change or early abscess formation. The
there will be an associated known high-grade malig-
diagnosis is acute coalescent mastoiditis with an early abscess in the nant tumor. Enhancement along the course of the facial
overlying soft tissues. nerve will be seen. The nerve can also appear to be

A B

C
Figure 18-7 A: Axial computed tomographic (CT) scan demonstrating a soft tissue mass within the left lateral tympanic cavity eroding malleus
and incus. B: At a slightly caudal level, axial CT scan demonstrating the soft tissue mass eroding the long process of incus. Extension of this soft tissue
mass into the external auditory canal is also seen. C: Coronal reformatted CT scan demonstrating erosion of the ossicles and scutum, and widening of
the Prussak space. The normal right scutum (arrowhead) and Prussak space (curved arrow) are shown for comparison. The diagnosis is cholesteatoma.
 Chapter 18 Head and Neck Radiology 561

t­ hickened. Facial nerve schwannoma will demonstrate peripheral calcification. Flow-related artifact can be seen

SECTION IV
fusiform thickening of the facial nerve. Variable degrees on MRI. Contrast-enhanced MR angiogram and CT
of enhancement will be seen. angiogram are diagnostic (Figure 18-9, D). Congenital
cholesteatoma will appear hypointense on T1-WI and
Cholesterol Granuloma will not exhibit any enhancement. Depending on its
protein content, mucocele can demonstrate variable
Cholesterol granuloma is the most common petrous signal intensity characteristics on T1-WI and T2-WI. It
apex lesion. Most patients are young adults who present can sometimes be difficult to distinguish a cholesterol
with tinnitus, hearing loss, and hemifacial spasms. On granuloma from a mucocele.
imaging, CT scan demonstrates an expansile lytic lesion
involving the petrous apex. The lesion appears hyper- Glomus Jugulare
intense on T1-weighted imaging (T1-WI), hyperintense
on T2-WI, and does not demonstrate any enhancement. Glomus jugulare is a paraganglioma that arises in the
The characteristic hyperintense signal seen on T1-WI is jugular fossa from paraganglia located within the adven-
highly suggestive of cholesterol granuloma (Figure 18-9, titia of the jugular bulb. Most patients present with dys-
A and B). Occasionally, fluid–fluid level secondary to phagia and hoarseness of voice. Cross-sectional imaging
intralesional hemorrhage can be seen. Differential diag- demonstrates an intensely enhancing lesion centered in
nosis includes chondrosarcoma, aneurysm of the petrous the jugular foramen. The demonstration of an irregularly
internal carotid artery, congenital cholesteatoma, and marginated lesion on CT and “salt-and-pepper” appear-
mucocele. Chondrosarcoma will demonstrate rings and ance on T2-weighted MRI are highly suggestive of glomus
arcs of calcification within the lytic lesion (Figure 18-9, jugulare (Figure 18-10, A–D). “Salt” refers to the hemor-
C). The lesion will appear hypointense on T1-WI and rhage and “pepper” to the flow voids seen in most such
exhibit heterogeneous enhancement following contrast lesions. Differential diagnosis includes schwannomas,
administration. An aneurysm can be seen as an expans- meningiomas, and metastasis. Typically, schwannomas
ile lytic lesion within the temporal bone ­demonstrating will demonstrate a lesion with smooth, rounded bor-
ders. No irregular bone destruction will be seen. Also,
schwannomas appear more homogeneous on MRI and
do not demonstrate the salt-and-pepper appearance of
glomus tumors (Figure 18-10, E–H). Meningiomas will
be associated with hyperostosis. An enhancing dural tail,
although not specific, is more often seen with meningio-
mas than with glomus tumors. A primary tumor will be
known in most patients with metastasis.

Acoustic Schwannoma
A
Acoustic schwannomas account for 60% to 80% of
all cerebellopontine angle tumors. Most acoustic
schwannomas arise from the vestibular division of the
vestibulocochlear (VIII) nerve. Typically, patients present
with unilateral sensorineural hearing loss. Large acoustic
schwannomas can be evaluated by both CT and MR. An
enhancing lesion widening the internal auditory canal
and extending into the cerebellopontine angle cistern
producing an “ice-cream cone” appearance will be seen.
B Some such acoustic schwannomas are associated with
cysts, typically along the medial margin of the lesion.
Intracanalicular schwannomas are best evaluated by
high-resolution MRI of the internal auditory canal. CT
imaging can be limited in evaluation. Bilateral acoustic
schwannomas are diagnostic of neurofibromatosis type
2 (NF2) (Figure 18-11). Differential diagnosis includes
meningiomas, epidermoids, and arachnoid cysts. Menin-
giomas in the cerebellopontine angle cistern will be
C associated with hyperostosis of the petrous pyramid. A
dural tail, although not specific, is more often seen with
Figure 18-8 A, B: High-resolution, fat-suppressed, contrast-enhanced meningiomas than with glomus tumors. Epidermoids in
axial T1-weighted imaging through the temporal bones demonstrating the cerebellopontine angle cistern will be seen as non-
asymmetric enhancement of the labyrinthine segment (arrow) and pos- enhancing cystic lesions that will typically demonstrate
terior tympanic segment (arrowhead) of the right facial nerve. C: High-
resolution, fat-suppressed, contrast-enhanced coronal T1-weighted
restricted diffusion. Arachnoid cysts in the cerebellopon-
imaging demonstrating asymmetric enhancement of the mastoid seg- tine angle cistern will be seen as nonenhancing cystic
ment (curved arrow) of the right facial nerve. The diagnosis is Bell’s palsy. lesions that will not demonstrate any restricted diffusion.
562 Section IV Problem Solving: Anatomic Regions

A B

C D
Figure 18-9 A: Axial computed tomographic (CT) scan demonstrating an expansile lytic lesion (star) in the left petrous apex. B: In a differ-
ent patient, axial T1-weighted imaging demonstrating a rounded homogeneously hyperintense lesion at the petrous apex. The diagnosis in both
of these patients is cholesterol granuloma. C: In another patient, axial CT scan demonstrating an expansile lytic lesion at the right petrous apex
showing faint rings and arcs of calcification. The diagnosis in this patient is a chondrosarcoma. D: In yet another patient, coronal reformatted CT
angiogram demonstrating a saccular aneurysm at the left petrous apex (Image courtesy: Shyamsunder Sabat, University of Alabama, Birmingham).

ORBIT
been reported. MR demonstrates a well-defined, lobu-
Eight cases are discussed in this section, including con- lated lesion hypointense on T1-WI and hyperintense on
genital vascular malformations (e.g., hemangiomas), T2-WI, which demonstrates avid contrast enhancement
orbital venous varix, trauma (e.g., orbital blowout frac- (Figure 18-12). Flow voids and calcification are some-
tures), infectious and inflammatory conditions (e.g., times seen. Differential diagnosis of capillary hemangi-
orbital cellulitis, Sjögren syndrome, Graves disease), oma includes lymphangioma and rhabdomyosarcoma.
tumors (e.g., lymphoma), and optic nerve gliomas. Lymphangiomas typically are transspatial and do not
demonstrate obvious enhancement. Rhabdomyosarco-
Vascular Malformations: mas are seen as destructive lesions, eroding and not just
scalloping the bones. Differential diagnosis of cavernous
Hemangiomas
hemangioma includes schwannoma and hemangioperi-
There are two types of hemangiomas: capillary and cav- cytoma. Schwannomas typically occur along the course
ernous hemangiomas. Capillary hemangiomas typically of cranial nerves III, IV, and VI. These lesions appear as
are absent at birth but demonstrate rapid growth dur- well-defined soft tissue lesions hypointense on T1-WI
ing infancy and spontaneous involution later in life. In and hyperintense on T2-WI, and demonstrate mild to
contrast, cavernous hemangiomas typically are seen in moderate contrast enhancement. Hemangiopericytomas
middle-aged adults. Most often unilateral, these lesions are rare intraorbital lesions that demonstrate intense
are classically located in the retrobulbar compartment early enhancement following contrast administration.
and demonstrate slow progressive enlargement. Most
patients with capillary hemangioma are brought in by Orbital Venous Varix
parents who notice a red periorbital area that blanches
on pressure. Most patients with cavernous hemangioma Orbital varix is the most frequently encountered pri-
present with ocular discomfort. Both lesions are seen on mary orbital venous abnormality. Patients usually are
CT as relatively well-defined lesions that demonstrate asymptomatic, but some may complain of intermittent
intense enhancement following contrast administration. proptosis, especially with a Valsalva-type maneuver. On
Less commonly, mild to moderate enhancement has imaging, a focal or segmental dilation of the superior
 Chapter 18 Head and Neck Radiology 563

SECTION IV
A B

C D
Figure 18-10 A: Contrast-enhanced axial computed tomographic (CT) scan demonstrating an irregularly marginated lytic lesion (star) in
the right jugular foramen. Axial T1-weighted imaging (B), axial T2-weighted imaging (C), and contrast-enhanced axial T1-weighted imaging
(D) demonstrating a heterogeneously enhancing lesion within the jugular foramen. The lesion demonstrates hypointense foci representing flow
voids and hyperintense foci representing hemorrhage, producing the characteristic salt-and-pepper appearance of a glomus tumor. The diagnosis
in this patient is glomus jugulare.
Continued

ophthalmic vein will be seen. Occasionally, the entire inherently weak floor of the orbit, typically along the
superior ophthalmic vein will be seen to be asymmetri- infraorbital foramen. The orbital rim classically remains
cally enlarged. Further dilation of the superior ophthal- intact. Fracture involving the floor of the orbit will be
mic vein can occur following a Valsalva-type maneuver seen on CT studies (Figure 18-14). Enophthalmos is
(Figure 18-13). Differential diagnosis includes carotid an ocular emergency and therefore should be evalu-
cavernous fistula, cavernous sinus thrombosis, and ated. Inferior rectus entrapment is also a medical emer-
orbital vascular malformation. In direct carotid–cavern- gency; however, it is a clinical diagnosis. Thus, although
ous fistula, an enlarged ipsilateral cavernous segment entrapment of the inferior rectus can be suggested, it can
of the ipsilateral carotid artery will be seen. In indirect never be diagnosed solely on imaging. Associated frac-
carotid–cavernous fistula, an arteriovenous fistula can tures, including those of the nasal bones and maxilla,
be demonstrated on an angiogram. Also, reversal of flow are common and should be assessed.
will be seen in the superior ophthalmic vein. Cavernous
sinus thrombosis will be seen as a filling defect in the Ocular Cellulitis
cavernous sinuses. Orbital vascular malformation will
demonstrate arterial feeders and a nidus. Ocular cellulitis can be broadly classified into pre-
septal cellulitis and postseptal (orbital) cellulitis. Of
the two, postseptal cellulitis has a higher morbidity
Orbital Blowout Fracture
and therefore requires more aggressive treatment.
Orbital blowout fracture results from direct blunt trauma The most common cause of orbital cellulitis is sinus-
to the orbit. The sudden increase in intraorbital pressure itis. Most patients will present with orbital pain and
from such an injury results in a fracture involving the swelling. Occasionally, patients complain of reduced
564 Section IV Problem Solving: Anatomic Regions

extraocular motility. CT and MRI will demonstrate guishing these different clinical entities can be difficult,
stranding of the periorbital fat. It is important to dis- but clinical and laboratory correlation can help to estab-
tinguish preseptal from postseptal cellulitis based on lish the diagnosis.
the infiltration of the fat and the presence of soft tis-
sue with respect to the orbital septum (Figure 18-15). Graves Disease with Characteristic
It also is imperative to evaluate for sinusitis and for Thyroid Orbitopathy
associated abscess.
Graves disease is an autoimmune disease character-
Sjögren Syndrome ized by hyperthyroidism. It frequently affects women
between the ages of 20 and 45 years. Most patients pres-
Sjögren syndrome is a systemic autoimmune disorder ent with signs and symptoms of hyperthyroidism with
characterized by lymphocytic infiltration of the exo- diffuse enlargement of the thyroid gland and infiltra-
crine glands. Most patients present with sicca symp- tive orbitopathy. On imaging, bilateral enlargement of
toms (e.g., xerophthalmia [dry eyes], xerostomia [dry the muscle bellies of the extraocular muscles sparing
mouth], parotid gland enlargement). In the orbit, the tendinous insertions will be seen (Figure 18-17).
Sjögren syndrome is characterized by bilateral lacri- Although any extraocular muscle can be involved, the
mal gland enlargement, which can be demonstrated on inferior rectus is most often affected. Associated orbital
both CT and MRI. Other associated findings in the head findings include increased deposition of retrobulbar
and neck include small cystic changes in the parotid fat, which results in proptosis. Differential diagnosis of
glands. Such cystic changes are best demonstrated on enlarged extraocular muscles includes myositis, pseudo-
T2-WI ­(Figure 18-16). Differential diagnosis of bilateral tumor, and metastasis. In each of these clinical entities,
lacrimal gland enlargement includes lymphoma, sar- unilateral orbital involvement is more common. Also,
coidosis, and pseudotumor. Based on imaging, distin- both the muscle bellies and the tendinous insertions

E F

G H
Figure 18-10, cont’d E: In a different patient, contrast-enhanced axial CT scan demonstrating a smoothly marginated lytic lesion (dia-
mond) in the right jugular foramen. Axial T1-weighted imaging (F), axial T2-weighted imaging (G), and contrast-enhanced fat-suppressed axial
T1-weighted imaging (H) demonstrating a homogeneously enhancing lesion. No abnormal flow voids or hemorrhages are associated with this
lesion. The diagnosis in this patient is vagal schwannoma.
 Chapter 18 Head and Neck Radiology 565

tend to become involved, a key distinguishing feature ary (80%) to lymphoid involvement from extraorbital

SECTION IV
from Graves disease. origins. Most primary lymphomas affecting the lacri-
mal gland are of mucosa-associated lymphoid tissue
Lymphoma (MALT) type. These tumors carry a better prognosis than
the more common secondary lymphoma of the orbit.
Lymphoma involvement of the lacrimal glands can be On imaging, homogeneous enlargement of unilateral
primary (20%) in origin (i.e., from native lymphoid or bilateral lacrimal glands is seen. Associated propto-
tissue present within the lacrimal glands) or second- sis and scalloping of the adjacent bone can be seen
(Figure 18-18). Differential diagnosis of bilateral lacri-
mal gland enlargement is discussed in the section on
Sjögren syndrome. Differential diagnosis of unilateral
lacrimal gland enlargement includes pseudotumor,
pleomorphic adenoma, and malignant tumors such as
adenoid cystic carcinoma. It can be difficult to distin-
guish pseudotumor and pleomorphic adenoma from
lymphoma. Adenoid cystic carcinoma will appear more
heterogeneous and can demonstrate bone destruction.

A
Optic Nerve Glioma
Optic nerve gliomas are low-grade neoplasms that can
affect any portion of the optic nerve. They can be unilat-
eral or bilateral. When bilateral, they are highly sugges-
tive of neurofibromatosis type 1 (NF1). They are often
seen in the first decade of life. Most often patients pres-
ent with proptosis and progressive decrease in visual acu-
ity. MR is better than CT in evaluating for optic nerve
gliomas. Typically, enlargement of the involved portion
B
of the optic nerve is seen. Variable degrees of enhance-
ment have been noted following contrast administra-
tion (Figure 18-19, A–C). Differential diagnosis includes
optic nerve sheath meningioma and optic neuritis. Optic
nerve sheath meningioma is characterized by enhance-
ment and thickening of the optic nerve sheath. The optic
nerve itself is spared. This results in the classic tram-track
sign of enhancement on contrast-enhanced MR studies
(Figure 18-19 D). Optic neuritis is characterized by an
C enhancing optic nerve with no evidence of any obvious
thickening (Figure 18-19 E). Most patients with optic
Figure 18-11 A: High-resolution constructive interference in steady- neuritis have an acute presentation of a painful eye, with
state (CISS) image demonstrating a focal soft tissue lesion within the
left internal auditory canal. B: High-resolution contrast-enhanced fat- sudden loss of vision.
suppressed axial T1-weighted imaging demonstrating enhancement of
the lesion. The diagnosis in this patient is an intracanalicular acous-
tic schwannoma. C: In a different patient, high-resolution, contrast- SINONASAL CAVITIES
enhanced, fat-suppressed axial T1-weighted imaging demonstrating
focal enhancing lesions (left larger than right) within both internal audi-
Six cases are discussed in this section. They include
tory canals. The diagnosis in this patient is bilateral acoustic schwanno- trauma (e.g., Le Fort I fractures), infectious and inflam-
mas diagnostic of neurofibromatosis type 2 (NF2). matory conditions (e.g., sinonasal polyposis, mucocele,

A B C
Figure 18-12 Axial T1-weighted imaging (A), axial T2-weighted imaging (B), and contrast-enhanced fat-suppressed axial T1-weighted imaging
(C) demonstrating left-sided proptosis with a large multilobulated lesion in the retrobulbar compartment of the left orbit appearing hypo- to iso-
intense on T1-weighted imaging and hyperintense on T2-weighted imaging, and demonstrating moderate heterogeneous enhancement. Smaller
components of this large lesion showing similar imaging characteristics are seen medial to the medial rectus. The diagnosis is cavernous hemangioma.
566 Section IV Problem Solving: Anatomic Regions

A B
Figure 18-13 A: Contrast-enhanced axial computed tomographic (CT) scan demonstrating a dilated tortuous right superior ophthalmic vein.
B: Contrast-enhanced axial CT scan following Valsalva maneuver demonstrating further increase in the caliber of the dilated superior ophthalmic
vein. The cavernous sinuses do not demonstrate any filling defect (ruling out cavernous sinus thrombosis) or any asymmetric prominence (ruling
out carotid cavernous fistula). The diagnosis is orbital venous varix.

A B C
Figure 18-14 A: Coronal computed tomographic (CT) scan, bone window demonstrating a fracture involving the floor of the left orbit.
B: Reformatted sagittal CT scan, bone window demonstrating the fracture involving the midportion of the floor of the orbit. The orbital rim is
intact. C: Coronal CT scan, soft tissue window demonstrating the inferior rectus is adjacent to the fracture site, raising the possibility of inferior
rectus entrapment. However, it should be noted that inferior rectus entrapment is a clinical diagnosis and can only be suggested but not diagnosed
on imaging. Hyperdensity seen within the maxillary sinus represents hemorrhage. The diagnosis is orbital blowout fracture.

A B
Figure 18-15 A: Axial computed tomographic scan demonstrating ill-defined soft tissue and stranding of periorbital fat predominantly within
the preseptal compartment of the left orbit. Extension into the postseptal compartment is also seen. Shrunken right globe demonstrates dys-
trophic calcification. The diagnosis in this patient is left orbital cellulitis and right phthisis bulbi. B: Contrast-enhanced, fat-suppressed, axial
T1-weighted imaging demonstrating left ethmoid sinusitis, a peripherally enhancing collection in the subperiosteal compartment, enhancement
and thickening of the left medial rectus, and stranding of the retrobulbar fat. The diagnosis in this patient is left ethmoid sinusitis with subperi-
osteal abscess, myositis, and postseptal cellulitis.
 Chapter 18 Head and Neck Radiology 567

SECTION IV
A B C
Figure 18-16 Coronal T1-weighted imaging (A), coronal T2-weighted imaging (B), and contrast-enhanced, fat-suppressed, axial T1-weighted
imaging (C) through both orbits demonstrate enlarged, enhancing lacrimal glands bilaterally. The diagnosis is Sjögren syndrome.

apices, and the zygomaticomaxillary junction, to involve

the pterygoid plates. Le Fort II fracture results from a blow
delivered to the central facial region. It is one of the most
severe of the facial fractures. The fracture extends through
the root of the nose to involve the frontal processes of
the maxilla, the lacrimal bones, the inferior orbital floor,
to extend under the zygoma, across the pterygomaxillary
fissure to involve the pterygoid plates. Le Fort III fracture
results from a blow to the central to upper midface. It is
regarded as the most severe of all facial fractures. This
fracture starts at the root of the nose and extends posteri-
orly along the lacrimal bones and the medial wall of the
orbit, to involve the floor of each orbit. The fracture then
continues superolaterally through the lateral orbital wall
and the zygomatic arch to involve the pterygoid plates
and the base of the sphenoid. Most patients present with
A facial swelling, bleeding, and crepitus. Reduced visual
acuity, paresthesia along the infraorbital nerve distribu-
tion, loose teeth, and malocclusion are other common
symptoms. Facial fractures are best evaluated with CT
scans complemented with three-dimensional recon-
structions. Typically, Le Fort I fractures are seen to extend
through the lower nasal septum, across the maxillary
alveolar rim and the zygomaticomaxillary junction, to
involve the pterygoid plates (Figure 18-20).

Sinonasal Polyposis
Sinonasal polyposis is inflammatory polypoidal change
involving the paranasal sinuses and nasal cavity. The
B
most common underlying etiology is seasonal pollino-
Figure 18-17 Coronal T1-weighted imaging (A) and axial sis, most commonly associated with ragweed allergy.
T1-weighted imaging (B) demonstrating enlargement of muscle bel- Other causes of pansinusitis include cystic fibrosis,
lies of most of the extraocular muscles bilaterally. Sparing of the ten- immotile cilia syndrome, and unusual allergens such
dinous insertions (arrows) can be appreciated on the axial image. The
diagnosis is Graves disease with characteristic thyroid orbitopathy.
as aspirin intolerance. Most patients present with nasal
obstruction, running nose, and headache. Common
radiologic manifestations include near-complete to
fungal sinusitis), and tumors (e.g., olfactory neuroblas- complete opacification of the paranasal sinuses and
toma, squamous cell carcinoma). nasal cavities with mucosal inflammatory change and
polyps (Figure 18-21). Bony scalloping of the sinus
walls is occasionally seen.
Le Fort I Fractures
Le Fort fractures account for 10% to 20% of all facial frac- Mucocele
tures. There are three types of Le Fort fractures. Le Fort I
fracture results from a blow delivered low on the maxil- Mucoceles are cystic expansile lesions of the paranasal
lary alveolar rim. The fracture extends through the lower sinuses, which are formed due to ostial obstruction. The
nasal septum, the maxillary alveolar rim above the teeth frontal and ethmoid sinuses are often involved. Most
568 Section IV Problem Solving: Anatomic Regions

A B
Figure 18-18 A: Contrast-enhanced axial computed tomographic (CT) scan, soft tissue window demonstrating asymmetrically enlarged,
enhancing right lacrimal gland. B: Corresponding axial CT scan, bone window demonstrating mild scalloping of the adjacent superolateral orbital
wall. The diagnosis is primary orbital (mucosa-associated lymphoid tissue) lymphoma.

A B C

D E
Figure 18-19 Axial T2-weighted imaging (A), coronal T2-weighted imaging (B), and contrast-enhanced axial T1-weighted imaging (C) dem-
onstrating enlarged enhancing optic nerves bilaterally. The diagnosis is bilateral optic nerve gliomas in this child with neurofibromatosis type
1 (NF1). D: In a different patient, contrast-enhanced, fat-suppressed, axial T1-weighted imaging demonstrating thickened, enhancing left optic
nerve sheath surrounding the optic nerve producing the tram-track sign diagnostic of optic nerve sheath meningioma. E: In another patient,
contrast-enhanced, fat-suppressed, coronal T1-weighted imaging demonstrating asymmetric enhancement of the left optic nerve. The diagnosis
in this patient is optic neuritis.

patients present with nasal obstruction, facial discom- ­ eoplasms. Typically, sinonasal polyposis involves
n
fort, and headache. Common radiologic manifestations almost all the paranasal sinuses. Benign sinonasal neo-
include an expansile cystic lesion involving the para- plasms (e.g., retention cysts, focal polyps) appear as focal
nasal sinuses. Thinning of the walls of the paranasal cystic lesions within the paranasal sinuses. They typi-
sinuses with occasional pressure deossification and ero- cally do not expand the paranasal sinuses. Other benign
sion can be seen. Most such cystic lesions are hypoin- polyps (e.g., antrochoanal polyps) will demonstrate
tense on T1-WI and hyperintense on T2-WI, and do not a soft tissue component. The typical growth pattern of
exhibit any contrast enhancement. Variable signal inten- antrochoanal polyp expanding the maxillary sinus and
sity within the mucocele can be seen due to variability in extending into the nasal cavity helps distinguish it from
the hydration state and protein content of these lesions other lesions (Figure 18-22, E). Aggressive sinonasal
­(Figure 18-22). The differential diagnosis includes sino- neoplasms will demonstrate an enhancing soft tissue
nasal polyposis, and benign and aggressive ­sinonasal mass with associated destruction of the sinus walls.
 Chapter 18 Head and Neck Radiology 569

SECTION IV
A B

C D
Figure 18-20 A–C: Coronal reformatted computed tomographic scans demonstrating a fracture line traversing through the frontal processes
of the maxillae (arrowheads), the right zygomaticomaxillary junction (arrow), and the pterygoid plates (curved arrows). Three-dimensional surface-
shaded display (3D-SSD) demonstrates the fracture line (arrowheads) coursing through the nasal septum, across the frontal processes of the maxil-
lae to extend further laterally to involve the region adjacent to the right zygomaticomaxillary junction. The diagnosis is Le Fort I fracture.

can be classified into fungal ball (or mycetoma) or

allergic fungal sinusitis. The invasive form is typically
seen in immunocompromised patients and has been
classified as acute fulminant fungal sinusitis, granulo-
matous invasive fungal sinusitis, and chronic invasive
fungal sinusitis. The noninvasive form is more indo-
lent in presentation. Headache, facial pain, and numb-
ness are typical presenting features. The invasive form
is more acute in presentation. Fever and headache are
typical presenting features. CT scan is the imaging
modality of choice. However, in patients with the inva-
sive form of fungal sinusitis, MRI with contrast may be
obtained to evaluate for intracranial involvement and
extension into the adjacent soft tissues. Fungal concre-
tions are typically seen as hyperdense foci within the
abnormal soft tissue seen within the paranasal sinuses.
Figure 18-21 Coronal reformatted computed tomographic scan More specifically, a fungus ball or mycetoma will
demonstrating polypoid mucosal thickening involving all the visual-
ized paranasal sinuses and the nasal cavity. There is mild bowing of
be seen as either a hyperdense area within the sinus
the bony walls of the nasal cavity. The diagnosis is sinonasal polyposis. cavity or as a focus of calcific density of varying size
within the inflammatory soft tissue mass in the para-
Fungal Sinusitis nasal sinuses. Allergic fungal sinusitis has nonspecific
imaging findings such as polypoid mucosal thicken-
Fungal diseases of the paranasal sinuses can be catego- ing. Invasive fungal sinusitis presents as inflamma-
rized into noninvasive and invasive varieties. The non- tory mucosal thickening completely opacifying the
invasive form seen in immunocompetent individuals involved paranasal sinuses. Spread to adjacent regions
570 Section IV Problem Solving: Anatomic Regions

A B C

D E
Figure 18-22 A: Coronal reformatted computed tomographic scan demonstrating an expansile cystic-appearing lesion involving the right
supraorbital ethmoid sinus (star) with pressure de-erosion of its inferior wall and inferior displacement of right ocular globe. Complete opacifica-
tion of the right frontal sinus is seen (diamond). B: Axial T2-weighted imaging demonstrating predominantly hyperintense signal within the right
supraorbital ethmoid sinus with fluid–fluid level suggestive of variability in the protein content of the lesion. Near-complete opacification of right
frontal sinus is seen. C: Contrast-enhanced coronal T1-weighted imaging demonstrating no obvious enhancement. D: Axial diffusion-weighted
imaging does not demonstrate any restricted diffusion. The diagnosis is right supraorbital ethmoid mucocele with right frontal sinusitis. E: Axial
CT scan through the maxillary sinuses demonstrates soft tissue lesion extending from one left maxillary sinus extending into the nasal cavity. The
lesion demonstrates a polypoidal configuration suggestive of an antrochoanal polyp.

A B
Figure 18-23 A 25-year-old man with a known case of bone marrow transplant and paranasal sinus surgery in the recent past presented with
fever, headache, and sinusitis. A: Axial computed tomographic (CT) scan demonstrating evidence of prior paranasal sinus surgery. Hyperdense
foci (arrowheads) are seen within nearly completely opacified bilateral maxillary sinuses. B: Axial CT scan at a more caudal level demonstrating
infiltration of fat in the region of the pterygomaxillary fissures (arrows) bilaterally. Completely opacified sphenoid sinuses are seen. The diagnosis
is fungal sinusitis.

can be ­suspected when there is infiltration of fat in the Occasionally, reactive sclerosis alternating with areas
adjacent soft tissues including the cheek, orbit, and of bony destruction is seen on the affected sinus walls.
infratemporal fossa (Figure 18-23). In immunocom- Intracranial extension is better assessed with MRI.
promised patients, such spread with intact sinus walls Dural thickening, empyema, intracranial abscess, and
should raise a red flag for invasive fungal sinusitis. mycotic aneurysms can occur.
 Chapter 18 Head and Neck Radiology 571

SECTION IV
A B

C D
Figure 18-24 A: Contrast-enhanced axial computed tomographic scan demonstrating a lobulated enhancing mass (star) in the posterior nasal
cavity. The mass extends into the left pterygomaxillary fissure (curved arrow). Subtle anterior bowing of the posterior wall of the left maxillary
sinus is seen. B: Axial T2-weighted imaging demonstrating a lobulated heterogeneous mass in the posterior nasal cavity. C: Contrast-enhanced
fat-suppressed axial T1-weighted demonstrates intense enhancement of this mass is seen following contrast administration on the contrast-
enhanced, fat-suppressed, axial T1-weighted image. D: Digital subtraction angiogram demonstrating tumor blush from arterial feeders arising
from the left internal maxillary artery. The diagnosis is juvenile nasopharyngeal angiofibroma.

Juvenile Nasopharyngeal
Angiomatous polyp is an uncommon soft tissue
Angiofibroma
lesion, typically seen in adult males. Although it is
Juvenile nasopharyngeal angiofibroma is a locally typically located in the posterior nasal cavity, it does
aggressive, benign hypervascular tumor found exclu- not exhibit extension into the infratemporal fossa or
sively in adolescent males. Most patients present with sphenoid sinus. The lesion does not cause anterior
nasal stuffiness and epistaxis. Imaging demonstrates bowing of the posterior wall of the maxillary sinus,
an intensely enhancing mass centered in the region which is typically seen in cases of juvenile nasopha-
of the sphenopalatine foramen (posterior nasal cavity ryngeal angiofibroma.
region). Extension contiguously anteriorly into nasal
cavity, posteriorly and inferiorly into the nasopharynx, Olfactory Neuroblastoma
laterally via the pterygomaxillary fissure into the infra-
temporal fossa, and posterosuperiorly into the sphe- Olfactory neuroblastoma (historically referred to as esthe-
noid sinus is typically seen. Extension into the middle sioneuroblastoma) is a rare malignant tumor of the nasal
cranial fossa is rarely seen. Juvenile ­nasopharyngeal cavity. It accounts for up to 6% of all malignant tumors
angiofibroma typically scallops adjacent bony struc- of the nasal cavity. It arises from the olfactory neuroepi-
tures and widens fissures through which it extends thelium, which extends from the roof of the nasal cav-
(Figure 18-24). Erosion is seen, but later in the disease ity into the adjacent superior turbinates. Most patients
process. Differential diagnosis includes rhabdomyo- present with nasal obstruction and occasional epistaxis.
sarcoma and angiomatous polyp. Rhabdomyosar- A homogeneously enhancing nasal cavity mass is seen
coma is seen in children about 6 to 8 years of age or (Figure 18-25, A and B). Extension into the adjacent
in the late second decade of life. Mild to moderate paranasal sinuses is occasionally seen. Intracranial exten-
enhancement is seen. Bone destruction can be seen. sion can be identified by the presence of focal ­enhancing
572 Section IV Problem Solving: Anatomic Regions

A B C

D E F
Figure 18-25 A: Contrast-enhanced coronal reformatted computed tomographic (CT) scan demonstrating an enhancing polypoidal soft tissue
mass (star) in the right nasal cavity. B: More anteriorly, coronal reformatted CT scan demonstrating the polypoid soft tissue mass is attached to the
right cribriform plate. The diagnosis in this patient is olfactory neuroblastoma. C: In a different patient, contrast-enhanced sagittal T1-weighted
imaging demonstrating an enhancing homogeneously enhancing mass in the sinonasal cavities with intracranial extension. The lesion demon-
strates a cystic component (star) along the posterior aspect of its intracranial component. Obstructive sphenoid and frontal sinusitis is seen. The
diagnosis in this patient is also an olfactory neuroblastoma. In another patient, axial (D) and coronal (E) T2-weighted imaging demonstrate an
expansile left nasal cavity mass. This mass demonstrates heterogeneous signal with alternating bands of hyperintense and hypointense signal
producing a “cerebriform-like appearance.” Obstructive left maxillary sinusitis is seen. F: Contrast-enhanced, fat-suppressed, axial T1-weighted
imaging demonstrating heterogeneous enhancement. The diagnosis in this patient is inverted papilloma.

dura. Sometimes, intracranial extension is associated

SALIVARY GLANDS
with a cyst that occurs along the margins of the tumor.
Presence of such an associated intracranial cyst is highly Three cases are discussed in this section. They include
suggestive of olfactory neuroblastoma (Figure 18-25, C). infectious and inflammatory disorders (e.g., sialadenitis),
Differential diagnosis includes inverted papilloma, pleo- acquired immunodeficiency syndrome (AIDS)-related
morphic adenoma, lymphoma, and melanoma. Based parotid cysts, and tumors (e.g., pleomorphic adenoma).
on imaging, it can be difficult to distinguish a completely
intranasal olfactory neuroblastoma from these different
Sialolithiasis and Sialadenitis
clinical entities. However, inverted papilloma demon-
strates a cerebriform-like appearance on T2-WI, which Sialolithiasis most commonly affects the submandibu-
can help distinguish it from other polypoidal nasal cavity lar gland, less commonly the parotid gland, and uncom-
masses (Figure 18-25, D–F). monly the sublingual gland. Most patients present with
pain, swelling, and tenderness of the involved salivary
Squamous Cell Carcinoma gland. CT scan is the imaging modality of choice. Sialo-
liths are typically seen as well-defined hyperdense foci
Squamous cell carcinoma is the most common type within the main drainage duct of the gland or within
of malignancy arising in the nasal cavity and parana- the gland itself (Figure 18-27). Secondary sialectasis
sal sinuses. These carcinomas constitute over 80% of (dilation of the ducts and ductules) and sialadenitis
neoplasms of the paranasal sinuses. About 70% occur (enlarged involved salivary gland) are seen. Stranding
in the maxillary sinus, 12% in the nasal cavity, and the can be seen in the adjacent soft tissues. Rarely, secondary
remainder in the remaining sinuses and nasal vestibule. infection occurs, resulting in abscess formation.
Most patients present during the fifth to sixth decade
of life. Clinical presentation varies and includes rhinor-
AIDS-Related Parotid Cysts
rhea, epistaxis, and pain. CT, positron emission tomog-
raphy/CT, and MR can be used to evaluate squamous AIDS-related parotid cysts are benign lymphoepithelial
cell carcinoma. An enhancing aggressive mass lesion cysts that occur in patients who are positive for human
causing bone destruction is seen (Figure 18-26). Dif- immunodeficiency virus. Most patients present with
ferential diagnosis includes sinonasal undifferentiated painless swelling in the region of the parotid glands.
carcinoma, adenocarcinoma, melanoma, malignant Imaging demonstrates nonenhancing cystic lesions
lymphoma, Wegener granulomatosis, and metastasis. involving both parotid glands. Rarely, unilateral involve-
Based on imaging, it is difficult to distinguish these dif- ment is seen. AIDS-related parotid cysts are usually
ferent clinical entities. accompanied by enlarged nasopharyngeal lymphoid
 Chapter 18 Head and Neck Radiology 573

SECTION IV
A B C
Figure 18-26 Contrast-enhanced axial (A) and reformatted coronal (B) computed tomographic scans demonstrating an aggressive destructive
lesion involving the right maxillary sinus. C: Positron emission tomographic-computed tomographic imaging demonstrating increased uptake by
the mass seen in the right maxillary sinus. The diagnosis is squamous cell carcinoma involving the maxillary sinus.

A B C
Figure 18-27 A: Axial computed tomographic (CT) scan, bone window demonstrating multiple hyperdense foci (arrowheads) in the region of
the right floor of mouth suggestive of sialolithiasis. B: Axial CT scan, soft tissue window at a corresponding level demonstrating dilatation of the
right Wharton duct (arrow). C: Axial CT scan at more caudal level demonstrating an asymmetrically enlarged right submandibular gland sugges-
tive of sialadenitis.

tissue and cervical lymphadenopathy (Figure 18-28, A). seen. Variable degrees of contrast enhancement are seen
Differential diagnosis includes Warthin tumor, intra- following contrast administration (Figure 18-29). When
parotid lymph nodes, and Sjögren syndrome. Warthin large, they tend to have a lobulated contour that is
tumor is typically associated with an enhancing nodule highly suggestive of their diagnosis. Differential diagno-
along the periphery of the cyst (Figure 18-28, B). Intrap- sis includes Warthin tumor and other low-grade or high-
arotid lymph nodes are more solid appearing. The intra- grade neoplasms of the salivary glands. Warthin tumor
parotid cysts in Sjögren syndrome are much smaller than will typically demonstrate an enhancing nodule along
those of AIDS-related parotid cysts (Figure 18-28, C). the periphery of the cyst. It can be difficult to distin-
guish a low-grade malignant neoplasm from pleomor-
Pleomorphic Adenoma phic adenoma. Most high-grade malignant neoplasms,
such as mucoepidermoid carcinomas, will demonstrate
Pleomorphic adenoma is the most common benign sal- an irregular margin and appear hypointense on T2-WI.
ivary gland tumor. They most often involve the parotid
glands and less commonly involve the submandibular MASTICATOR SPACE, ORAL CAVITY
glands and minor salivary glands. Most patients present INCLUDING FLOOR OF MOUTH,
with a slow-growing mass. Both CT and MR can be used
AND PHARYNX
to evaluate pleomorphic adenomas. CT will demon-
strate a well-defined ovoid lesion with a slightly higher Six cases are discussed in this section. They include
attenuation than the surrounding parotid parenchyma. trauma (e.g., foreign body), infectious and inflamma-
Occasionally, the tumors have a more cystic appearance tory conditions (e.g., peritonsillar abscess), Ludwig
due to areas of necrosis. On MR, these tumors typically angina, and tumors (e.g., lingual tonsil squamous cell
appear hypointense on T1-WI and hyperintense on carcinoma, retromolar trigone carcinoma, rhabdomyo-
T2-WI. Occasionally, a low-signal-intensity “capsule” is sarcoma, ameloblastoma).
574 Section IV Problem Solving: Anatomic Regions

A B

C
Figure 18-28 A: Contrast-enhanced axial computed tomographic (CT) scan demonstrating multiple, nonenhancing cystic lesions within both
parotid glands. Note prominence of nasopharyngeal soft tissue. The diagnosis in this patient is AIDS-related parotid cysts and prominent naso-
pharyngeal soft tissue. B: In a different patient, contrast-enhanced axial CT scan demonstrating enhancing nodule (arrow) along the periphery of
the left parotid cyst. The diagnosis in this patient is Warthin tumor. C: In another patient, fat-suppressed axial T2-weighted imaging demonstrating
multiple subcentimeter cystic lesions within both parotid glands. The diagnosis in this patient is Sjögren syndrome.

Peritonsillar Abscess
the patient may experience a sensation of strangling as
Peritonsillar abscesses are more commonly seen in the inflammatory change pushes the tongue posteriorly,
the pediatric population. The most common organ- which can potentially block the oropharynx. Contrast-
isms associated with peritonsillar abscess are group A enhanced CT scan is the imaging modality of choice. It
beta-hemolytic streptococcus and fusobacterium. Most demonstrates a peripherally enhancing, predominantly
patients present with fever, sore throat, odynophagia, necrotic lesion suggestive of an abscess involving the
and occasionally otalgia. Contrast-enhanced CT will floor of mouth. Stranding of fat in the floor of mouth
demonstrate a predominantly necrotic peripherally and inflammatory change in the adjacent soft tissues are
enhancing lesion in the region of the tonsil, typically common (Figure 18-31). Reactive cervical lymphade-
in the (presumed) space between the tonsil and its cap- nopathy is also common. Rarely, osteomyelitis of the
sule (Figure 18-30). An enlarged retropharyngeal lymph mandible is seen. An accompanying history of dental
node is a common associated finding. caries, recent dental manipulation, or, less commonly,
history of sialolithiasis and sialadenitis involving the
submandibular gland helps establish the diagnosis.
Ludwig Angina
Differential diagnosis includes necrotic lymph node,
Ludwig angina is a serious, potentially life-threatening lymphangioma, and ranula. A known primary tumor or
infection of the floor of mouth, which most commonly other enlarged cervical lymph nodes will be seen with
occurs secondary to dental caries or manipulation. Most a necrotic level I (floor mouth) lymph node. Lymph-
patients present with fever, pain, and tenderness at the angioma classically presents as a nonenhancing multi-
floor of mouth. With more extensive spread of infection, loculated, transspatial lesion. No inflammatory changes
 Chapter 18 Head and Neck Radiology 575

SECTION IV
A B

C
Figure 18-29 A: Axial T1-weighted imaging demonstrating a well-defined, ovoid, predominantly hypointense lesion (star) within the right
parotid gland. B: Fat-suppressed axial T2-weighted imaging demonstrating the lesion is minimally hyperintense to the rest of the visualized
parotid gland. C: Contrast-enhanced, fat-suppressed, coronal T1-weighted imaging demonstrating near-homogeneous enhancement of this
lesion. The diagnosis is pleomorphic adenoma.

are seen. A ranula classically presents as a thin-walled, tumor for better staging and treatment planning (i.e.,
unilocular, well-defined, nonenhancing, cystic-appear- anteriorly into the oral tongue and sublingual space,
ing lesion in the lateral floor of the mouth arising from posterolaterally into palatine tonsil, and inferiorly into
the sublingual gland. Typically this cystic lesion remains supraglottic larynx). Also, cervical lymphadenopathy
above the mylohyoid muscle sling. No inflammatory should be evaluated. Differential diagnosis includes
changes are seen. lingual tonsil hyperplasia and minor salivary gland
malignancy. Asymmetric lingual tonsil hyperplasia can
Lingual Tonsil Squamous Cell sometimes mimic base of tongue carcinoma. However,
Carcinoma the enhancing mass lesion seen with base of tongue
carcinoma is not noted with lingual tonsil hyperpla-
Lingual tonsil squamous cell carcinoma, also known as sia. Based on imaging, it can be difficult to distinguish
base of tongue carcinoma, is seen as a mass lesion poste- minor salivary gland malignancy from base of tongue
rior to the circumvallate papilla, extending inferiorly to carcinoma.
the vallecula. Most such tumors remain clinically indo-
lent for a long time and are seen only when they are Retromolar Trigone Carcinoma
large. Patients typically have cervical lymphadenopathy
at the time of presentation. On imaging, an asymmetri- Usually retromolar trigone carcinomas are squamous
cally enhancing mass lesion is seen at the tongue base cell carcinomas. Excessive alcohol and tobacco abuse
(Figure 18-32). It is critical to evaluate the spread of are the most common risk factors. Most patients
576 Section IV Problem Solving: Anatomic Regions

A B C
Figure 18-30 A: Contrast-enhanced axial computed tomographic scan demonstrating a predominantly necrotic lesion involving the right ton-
sil. Inflammatory change is seen involving the adjacent right parapharyngeal space. Mass effect on the airway and midline shift to the left is seen.
The diagnosis in this patient is right peritonsillar abscess. B: In a different patient, axial T2-weighted imaging demonstrating a predominantly
necrotic lesion in the left peritonsillar region. C: Contrast-enhanced, axial T1-weighted imaging demonstrating peripheral enhancement of this
predominantly necrotic lesion suggestive of a peritonsillar abscess.

A B
Figure 18-31 A: Contrast-enhanced axial computed tomographic (CT) scan demonstrating a well-defined necrotic lesion in the left floor of the
mouth with adjacent inflammatory change. Note reactive thickening of the left oropharyngeal wall. The diagnosis in this patient is Ludwig angina.
B: In a different patient, contrast-enhanced axial CT scan demonstrating ill-defined inflammatory change, predominantly involving the right floor
of mouth adjacent to the submandibular gland. Pockets of air are seen scattered throughout the floor of mouth. Extensive reactive edematous
changes extend to involve the tongue base and oropharynx, resulting in near-complete occlusion of the airway. An endotracheal tube is seen in
situ. The diagnosis in this patient is also Ludwig angina. Purulent material obtained from an ill-defined collection in the right floor of mouth
demonstrated a mixture of aerobic and anaerobic flora, with gas-forming organisms (Klebsiella and anaerobic streptococci).
 Chapter 18 Head and Neck Radiology 577

SECTION IV
A B C
Figure 18-32 A: Contrast-enhanced axial computed tomographic (CT) scan demonstrating an ill-defined heterogeneous lesion (star) involving
the left tongue base. Extension anteriorly into the oral tongue and posteriorly into the left oropharynx is seen. There is no extension of the lesion
across the midline. B: Contrast-enhanced axial CT scan demonstrating a predominantly necrotic left level IIA lymph node (arrow) with extracap-
sular spread. C: Positron emission tomography/CT study demonstrates increased uptake at the left tongue base. The diagnosis is left tongue base
carcinoma with cervical lymphadenopathy.

A B
Figure 18-33 A: Contrast-enhanced axial computed tomographic (CT) scan at the level of the oral cavity demonstrating an ill-defined soft
tissue mass (arrow) in the right retromolar trigone. B: Contrast-enhanced axial CT scan at the level of the floor of the mouth demonstrating pos-
sible contiguous extension of the mass along the right oropharyngeal region. Extensive, necrotic right level I and II lymphadenopathy is seen. The
diagnosis is right retromolar trigone carcinoma and cervical lymphadenopathy.

­ resent with discomfort in the region of the oral cav-

p enhancing soft tissue mass with poorly defined margins.
ity or painless bleeding. On imaging, a mass lesion Bone remodeling and destruction are also noted (Figure
will be seen in the region of the retromolar trigone. 18-34). Differential diagnosis includes plexiform neu-
It is essential to map the tumor on imaging for better rofibroma and juvenile nasopharyngeal angiofibroma.
staging and treatment planning. Spread of the tumor Plexiform neurofibroma will demonstrate multiple ser-
into the masticator space usually portends a poor piginous or ovoid soft tissue lesions causing scalloping
prognosis (Figure 18-33). Cervical lymphadenopathy of the bone. Other features of NF1 may be seen. Juvenile
is seen in 20% to 30% of cases and should also be nasopharyngeal angiofibroma is seen as an intensely
assessed. enhancing mass in the region of the posterior nasal cav-
ity, extending into adjacent spaces. The lesion typically
Rhabdomyosarcoma extends into the infratemporal fossa, widening the pter-
ygomaxillary fissure and bowing the posterior wall of
Rhabdomyosarcoma is the most common soft tissue the maxillary sinus.
sarcoma in children. It shows a bimodal peak age pre-
sentation, at 2 to 5 years, and again at 15 to 20 years. Ameloblastoma
It is uncommonly seen in adults. Most patients present
with a slowly growing mass lesion. Occasionally trismus Ameloblastoma accounts for 10% of all odontogenic
is noted, especially when the temporomandibular joint tumors. It is the most common epithelial odontogenic
is involved. Imaging demonstrates a heterogeneously tumor and is typically seen in young adults. The lesion
578 Section IV Problem Solving: Anatomic Regions

A B
Figure 18-34 A: Contrast-enhanced coronal T1-weighted imaging demonstrating an enhancing lesion in the right masticator space with pos-
sible involvement of the ramus and condyle of the mandible. B: Axial computed tomographic scan demonstrating scalloping and erosion of the
ramus of the mandible. The diagnosis is rhabdomyosarcoma.

A B
Figure 18-35 Axial computed tomographic (CT) scan (A) and coronal reformatted CT scan (B) demonstrating predominantly lytic lesion
showing mild scalloping and thinning of the cortex involving ramus of right mandible. The diagnosis is ameloblastoma.

can involve the mandible or the maxilla, although the two clinical entities, metastasis only rarely involves the
most common site is the posterior body or ramus of the mandible.
mandible. Most patients present with a slow-growing
painless mass. Imaging demonstrates an expansile, uni- THYROID AND LARYNX
locular lesion seen in the posterior body or ramus of
the mandible (Figure 18-35). Sometimes a multilocu- Six cases are discussed in this section. They include con-
lar lesion is seen. Differential diagnosis includes odon- genital anomalies (e.g., lingual thyroid, thyroglossal
togenic keratocyst, dentigerous cyst, metastasis, and duct cyst), inflammatory conditions (e.g., Hashimoto
multiple myeloma. Odontogenic keratocyst is usually a thyroiditis, goiter), and neoplastic conditions (e.g., ana-
solitary lesion and can have the same imaging appear- plastic thyroid carcinoma, laryngeal carcinoma).
ance as ameloblastoma. However, a lesion located in the
posterior body or the ramus of the mandible is more Lingual Thyroid
likely to represent an ameloblastoma.
A dentigerous cyst usually has a tooth associated Ectopic thyroid tissue most commonly is located at the
with the cyst wall. Metastasis and multiple myelomas tongue base but can be found anywhere along its embry-
are usually seen as multiple lytic lesions, unlike typical, onic course (i.e., from the foramen cecum at the junction
solitary, more well-defined ameloblastomas. Of these of the anterior two thirds and posterior one third of the
 Chapter 18 Head and Neck Radiology 579

SECTION IV
A B
Figure 18-36 A: Contrast-enhanced axial computed tomographic (CT) scan at the level of the floor of the mouth demonstrating an enhancing
lesion (arrow) in the midline base of tongue. B: Contrast-enhanced axial CT scan at the level of the thyroid bed does not demonstrate any evidence
of normal native thyroid tissue. The diagnosis is ectopic thyroid with absent normal native thyroid tissue.

tongue up to its normal location in the neck). It is imper- adenopathy with or without a primary mass lesion will
ative to scan the thyroid bed in the neck for normal thy- be seen. Lymphangiomas typically appear as multilocu-
roid tissue if ectopic thyroid tissue is found. Most patients lated, transspatial, nonenhancing cystic lesions. Bran-
are asymptomatic. Some patients present with hypothy- chial cleft cysts are typically seen more laterally, typically
roidism. CT scan shows a well-defined, high-density in the posterior triangle of the neck.
lesion, which demonstrates intense enhancement at the
tongue base (or anywhere along the embryonic course of Hashimoto Thyroiditis
thyroid) (Figure 18-36). MR study demonstrates lingual
thyroid as a well-defined mass, hyperintense on both Hashimoto thyroiditis (chronic lymphocytic thy-
T1-WI and T2-WI. In such cases, a nuclear medicine scan roiditis) is an autoimmune form of thyroiditis. Most
should be obtained to evaluate for any other ectopic thy- patients are women in their third to fifth decade of
roid tissue sites and for any evidence of functioning thy- life who present with signs and symptoms of hypo-
roid tissue at its normal location. thyroidism. An association with lymphoma has been
described. In fact, a small percentage of patients with
Hashimoto thyroiditis develop malignant lymphoma
Thyroglossal Duct Cyst
of the thyroid gland, and most patients with thyroid
The thyroglossal duct cyst is the most common congeni- lymphoma have coexistent Hashimoto thyroiditis.
tal neck mass. It is classically seen as a cystic lesion in Diagnosis of Hashimoto thyroiditis is generally based
or just off the midline. The cysts result from failure of on clinical presentation and laboratory analysis of thy-
normal involution of the thyroglossal duct with subse- roid function. Imaging does not play a critical role in
quent cyst formation. Most patients present with a slow making the diagnosis. However, three distinct patterns
growing, nontender midline neck mass. Imaging dem- have been described on imaging: a large solitary nod-
onstrates thyroglossal duct cyst as a midline, unilocular ule, multiple small nodules, and diffuse infiltration
cystic lesion, at or just below the level of the hyoid bone of the gland (Figure 18-38). Violation of the thyroid
(Figure 18-37, A). In the lower neck, the thyroglossal capsule or presence of cervical lymphadenopathy sug-
duct cyst is seen just outside the thyroid cartilage, in gests an underlying lymphoma. Differential diagnosis
the midline or just off midline, and tends to insinuate includes de Quervain thyroiditis and goiter. Based on
itself between the strap muscles (Figure 18-37, B and imaging, it can be difficult to distinguish these clinical
C). The presence of solid tissue within a thyroglossal entities. Clinical and laboratory correlation is helpful
duct cyst could represent residual thyroid tissue (Figure in establishing the diagnosis.
18-37, D). However, coexistent thyroid carcinoma (usu-
ally papillary) merits consideration (Figure 18-37, E). Goiter
Differential diagnosis includes necrotic lymph node,
lymphangioma, and branchial cleft cyst. A necrotic Enlargement of the thyroid gland due to any cause
lymph node typically demonstrates a slightly thick is known as goiter. Patients can present with a neck
enhancing wall. Associated additional cervical lymph- mass and signs and symptoms of hyperthyroidism or
580 Section IV Problem Solving: Anatomic Regions

A B C

D E
Figure 18-37 A: Contrast-enhanced axial computed tomographic (CT) scan demonstrating a predominantly cystic lesion attached to
the hyoid bone in the midline neck. The diagnosis in this patient is thyroglossal duct cyst. B, C: In a different patient, contrast-enhanced
axial CT scans demonstrating a well-defined abnormal density lesion in the midline neck, attached to hyoid bone and insinuating itself
between the strap muscles. The slightly higher density seen within this lesion suggests a more proteinaceous content of the thyroglossal
duct cyst. D: In another patient, contrast-enhanced axial CT scan demonstrating soft tissue (arrow) along the margins of a cyst in midline
neck. This soft tissue was proven to be normal thyroid tissue within thyroglossal duct cyst. E: In yet another patient, contrast-enhanced,
fat-suppressed, axial T1-weighted imaging demonstrating irregularly marginated, heterogeneous enhancing lesion (arrowhead) within
the cyst in midline neck. This enhancing soft tissue was proven to be mixed papillary and follicular carcinoma within thyroglossal
duct cyst.

­ ypothyroidism. Rarely, patients present with dyspha-

h
gia and dyspnea due to esophageal and tracheal com-
pression. Of note, hoarseness does not occur in benign
enlargement of thyroid gland. In fact, presence of
hoarseness suggests underlying malignant transforma-
tion and recurrent laryngeal nerve paralysis. Heteroge-
neous enlargement of the thyroid gland is seen. Such
enlargement can affect a single lobe or can diffusely
involve the whole gland. Such enlargement can be focal
and remain confined to the vicinity of the thyroid bed,
or it can be more widespread, extending for a variable
distance along the pharynx superiorly or to a retroster-
nal location inferiorly (Figure 18-39). There is no viola-
tion of the thyroid capsule or cervical lymphadenopathy.
Narrowing and displacement of the trachea are seen and
should always be evaluated.
Figure 18-38 Contrast-enhanced axial computed tomographic
scan demonstrating heterogeneous enhancement of the thyroid gland. Anaplastic Thyroid Carcinoma
The thyroid gland enhances less than normal. The diagnosis is Hashi-
moto thyroiditis. Anaplastic thyroid carcinoma is the most aggressive variety
of thyroid malignancy. It accounts for less than 2% of all
thyroid cancers but is responsible for up to 40% of deaths
 Chapter 18 Head and Neck Radiology 581

SECTION IV
A B

C D
Figure 18-39 A: Contrast-enhanced axial computed tomographic (CT) scan demonstrating diffuse heterogeneous enlargement of the entire
thyroid gland including the isthmus (right lobe > left lobe). There is no violation of the thyroid capsule. Displacement of the trachea to the left
is seen with mild tracheal luminal compromise. B: Axial CT scan at a more cranial level demonstrating superior extension of the enlarged lobes
of the thyroid gland along the pharynx up to the level of the supraglottic larynx. The diagnosis in this patient is goiter. C: In a different patient,
contrast-enhanced axial CT scan demonstrating heterogeneous enlargement of the thyroid gland suggestive of goiter. Displacement of the trachea
to the right is seen with mild tracheal luminal compromise. There is no violation of the thyroid capsule. D: Caudally, axial CT scan demonstrating
retrosternal extension of goiter.
582 Section IV Problem Solving: Anatomic Regions

A B C
Figure 18-40 A: Contrast-enhanced axial computed tomographic (CT) scan demonstrating a heterogeneous mass lesion involving the left lobe
of the thyroid gland and extending through its capsule to involve the left sternocleidomastoid. B: Axial CT scan at a caudal level demonstrating
the mass to extend up to the skin surface with associated ulceration (arrowheads) along its margins. C: Axial CT scan at a more caudal level dem-
onstrating marginal extension into the trachea (arrow). The diagnosis is anaplastic thyroid carcinoma.

from thyroid cancers. Most patients are elderly women, Brachial Cleft Cyst II
who present with a rapidly growing neck mass, hoarseness,
dyspnea, and dysphagia. An aggressive heterogeneous thy- Branchial cleft cysts are congenital anomalies arising
roid-based mass lesion is seen violating its capsule, extend- from anomalous embryogenesis of the branchial arches.
ing into adjacent soft tissue structures including the trachea Depending on the arch involved, four such branchial
and larynx (Figure 18-40). Cervical lymphadenopathy is cleft cysts are seen in the neck. Of these, the type 2 bran-
common. Lung metastasis is not uncommon. Rarely, inva- chial cleft cyst is the most common. Most patients pres-
sion of vascular structures occurs. Hematogenous metasta- ent with a neck mass or some discomfort in the neck.
sis and brain metastasis are known. Differential diagnosis Imaging demonstrates a uniform thin-walled cyst pos-
includes other primary thyroid cancers, such as papillary, terolateral to the submandibular gland, anteromedial to
follicular, and medullary thyroid cancer. However, these the sternocleidomastoid and anterolateral to the carotid
thyroid cancers are not as aggressive in spreading to adja- sheath (Figure 18-42). Differential diagnosis includes
cent structures as is anaplastic thyroid cancer. necrotic lymph node, abscess, and lymphangioma. A
necrotic lymph node will demonstrate some periph-
Squamous Cell Carcinoma of Larynx eral thickening. In addition, a primary mass lesion and
additional lymphadenopathy will be seen. An abscess
Squamous cell carcinoma accounts for the overwhelm- will demonstrate a thick-walled peripherally enhanc-
ing majority of all malignancies of the larynx. Risk ing predominantly necrotic lesion. Lymphangiomas are
factors include alcohol, tobacco, and human papil- typically nonenhancing, multiloculated, multispatial
lomavirus. Most patients present with hoarseness of congenital lesions.
voice. An enhancing mass lesion will be seen on imag-
ing. However, the goal of imaging is not to identify the Cystic Hygroma
tumor but to determine the extent of tumor and evalu-
ate for metastasis. In particular, evaluation should be Cystic hygroma is the most common form of lymph-
performed to determine the presence of cartilage inva- angioma. The other less common varieties include cav-
sion and transglottic spread of tumor (Figure 18-41). ernous lymphangioma, capillary lymphangioma, and
This finding can have significant surgical implications, vasculolymphatic malformations. Cystic hygromas can
including voice conservation surgery and choice of treat- occur anywhere in the neck, but most are located in
ment protocol. In addition, extension of tumor across the posterior triangle of the neck. Most patients present
the anterior commissure to involve more than one third with a growing neck mass. Nonenhancing, multilocu-
of the contralateral larynx precludes vertical hemilaryn- lated, occasionally transspatial cystic lesion, sometimes
gectomy. Evaluation for cervical lymphadenopathy and demonstrating fluid–fluid level suggestive of intrale-
metastasis should also be performed. sional hemorrhage, is seen (Figure 18-43). Differential
diagnosis includes thyroglossal duct cyst and branchial
NECK MISCELLANEOUS cleft cysts. Thyroglossal duct cyst is typically seen in the
midline neck. These cysts are attached to, or are in close
Six cases are discussed in this section. They include proximity to, the hyoid bone and typically insinuate
congenital anomalies (e.g., branchial cleft cyst, cystic themselves between the strap muscles. The unilocu-
hygroma), trauma (e.g., foreign body), infectious and lar, nonseptated appearance of the branchial cleft cysts
inflammatory conditions (e.g., Lemierre syndrome), and their specific locations in the neck help distinguish
and tumors (e.g., carotid body tumor, lymphoma). branchial cleft cysts from lymphangiomas.
 Chapter 18 Head and Neck Radiology 583

SECTION IV
A B

C D
Figure 18-41 A: Contrast-enhanced axial computed tomographic (CT) scan demonstrating irregularly marginated soft tissue mass obliterating
the left pyriform sinus. B: Axial CT scan at a caudal level demonstrating mass lesion extending contiguously along the left true cord. There is a hint
of extension of this mass lesion across the left thyroid cartilage into the adjacent strap muscles (arrow) suggestive of cartilage invasion. C: Axial
CT scan at a more caudal level demonstrating irregularity along the left lateral aspect of the subglottis. D: Coronal reformatted CT scan confirms
findings demonstrated on axial scans of a heterogeneous mass (carcinoma) seen in the left supraglottic region with transglottic spread.
584 Section IV Problem Solving: Anatomic Regions

Carotid Body Tumor

Carotid body tumor is a type of paraganglioma. Most
paragangliomas are sporadic. Occasionally, they are
familial with autosomal dominant inheritance and
incomplete penetrance. In the head and neck, based on
their anatomic location, four types of paragangliomas
have been described. Paragangliomas that arise at the
nodose ganglion of the vagus nerve are known as glomus
vagale; those at the carotid body bifurcation are known
as carotid body tumors; those at the jugular foramen are
known as glomus jugulare; and those at the cochlear
promontory are known as glomus tympanicum tumors.
Most patients with carotid body tumor present with a
slowly growing pulsatile mass in the neck. On imaging,
an intensely enhancing mass at the carotid bifurcation,
splaying the internal and external carotid arteries, is seen
(Figure 18-46, A–D). Differential diagnosis includes
schwannoma and lymph nodes. A vagal schwannoma
is seen as a moderately enhancing lesion that typically
displaces the internal jugular vein posterolaterally and
internal carotid artery anteromedially (Figure 18-46,
Figure 18-42 Contrast-enhanced axial computed tomographic E and F). Lymph nodes are uncommonly seen in the
scan demonstrating a nonenhancing cystic lesion posterior to the carotid sheath. Typically, such lymphadenopathy will
submandibular gland (SMG), anterior to the carotid sheath (CS), and be associated with lymphadenopathy elsewhere in the
anteromedial to the sternocleidomastoid (SCM) suggestive of a type neck.
2 branchial cleft cyst.

Lymphoma
Foreign Body
Lymphoma is the second most common primary malig-
Most foreign bodies seen in the neck result from acci- nancy that occurs in the head and neck. It occurs as either
dental ingestion. Patients present with a foreign body Hodgkin disease or non-Hodgkin lymphoma. Hodgkin
sensation in the throat. Occasionally, dysphagia and disease (HD) predominantly affects adolescents and
dyspnea are also present. Most foreign bodies are iden- young adults, and it typically involves the lymph nodes.
tified as hyperdensities of varying shapes. Associated Extranodal disease is rare in head and neck. The diag-
retropharyngeal soft tissue swelling is seen, and can be nosis is established by the presence of Reed-Sternberg
appreciated on lateral scout film of the neck or lateral cells. Non-Hodgkin lymphoma (NHL) is most com-
plain film of the neck. The foreign body is best appreci- monly seen in older patients. Extranodal involvement
ated on CT scans (Figure 18-44). is seen in 60% cases of NHL, with areas rich in lym-
phoid tissue such as the Waldeyer ring, more prone to
Lemierre Syndrome such occurrence. Enlarged, homogeneously enhancing
cervical lymph nodes are typically seen, although non-
Lemierre syndrome is an anaerobic suppurative throm- homogeneous, necrotic lymph nodes uncommonly can
bophlebitis of the internal jugular vein, occurring most occur (Figure 18-47). Differential diagnosis includes
commonly secondary to pharyngeal, dental, or mas- tumors (e.g., leukemia, metastasis, posttransplant lym-
toidal infection. Most patients present with fever, sore phoproliferative disorder), infectious etiologies (e.g.,
throat, neck pain, and tenderness. Color Doppler ultra- cat-scratch disease, tuberculosis), and inflammatory
sound demonstrates a distended internal jugular vein, conditions (e.g., sarcoidosis, Kimura disease, Castleman
which does not demonstrate any flow within. Contrast- disease). Presence of necrosis and calcification raises the
enhanced CT scan demonstrates an enlarged jugular possibility of metastasis and infectious etiologies such
vein, with filling defect within the vein. Stranding of the as tuberculosis. However, it can sometimes be difficult
adjacent fat will be seen. Asymmetrically thickened ipsi- to establish the diagnosis on imaging. Therefore, lymph
lateral oropharyngeal wall is often seen (Figure 18-45). node biopsy is indicated in most cases.
 Chapter 18 Head and Neck Radiology 585

SECTION IV
A B

C D
Figure 18-43 A: Contrast-enhanced axial computed tomographic (CT) scan demonstrating nonenhancing, multiloculated, transspatial cystic
lesion in the region of the floor of mouth. Fluid level (arrowhead) seen within one of these loculations suggests intralesional hemorrhage. Axial
T1-weighted imaging (B), axial T2-weighted imaging (C), and contrast-enhanced fat-suppressed coronal T1-weighted imaging (D) confirm the
morphologic appearance of the lesion seen on CT study. The diagnosis is cystic hygroma.
586 Section IV Problem Solving: Anatomic Regions

A B

C
Figure 18-44 A: Noncontrast axial computed tomographic (CT) scan of the neck demonstrating a linear hyperdensity within the cervical
esophagus. The diagnosis in this patient is a swallowed chicken bone. B: In a different patient, lateral scout film demonstrating a toothbrush in the
hypopharynx with extensive heterogeneity of the soft tissues suggestive of emphysema. C: Noncontrast axial CT scan of the neck demonstrating
bristles of the toothbrush in the region of the left pyriform sinus with extensive emphysematous changes.

A B
Figure 18-45 A: Contrast-enhanced axial computed tomographic (CT) scan at the level of the true cords demonstrating a filling defect within
the right internal jugular vein (arrow) with adjacent inflammatory changes. B: Axial CT scan at the level of the oral cavity demonstrating asym-
metric thickening of the right oropharyngeal wall (star). The diagnosis is Lemierre syndrome.
 Chapter 18 Head and Neck Radiology 587

SECTION IV
A B C

D E F
Figure 18-46 A: Fat-suppressed axial T2-weighted imaging just distal to the carotid bifurcation demonstrating mass lesions (stars) displacing
the internal carotid arteries posteriorly and external carotid arteries anteriorly. B: Contrast-enhanced sagittal T1-weighted imaging demonstrat-
ing an intensely enhancing lesion splaying the internal carotid artery posteriorly (arrowheads) and external carotid artery anteriorly (arrow).
C: Contrast-enhanced time-resolved imaging of contrast kinetics (TRICKS) magnetic resonance angiography (MRA) image reconstructed in the
sagittal plane demonstrating tumoral blush at the carotid bifurcation. D: TRICKS MRA image in the coronal plane demonstrating tumoral blush
at the carotid bifurcation bilaterally. The diagnosis in this patient is bilateral carotid body tumors. E: In a different patient, axial T1-weighted imag-
ing demonstrating a soft tissue lesion displacing the left internal carotid artery anteromedially (black arrow) and internal jugular vein posteriorly
(curved arrow). F: Contrast-enhanced, fat-suppressed, axial T1-weighted imaging demonstrating enhancement of the mass. The diagnosis in this
patient is vagal schwannoma.

A B
Figure 18-47 A: Contrast-enhanced axial computed tomographic (CT) scan at the skull base demonstrating enlarged suboccipital and intrapa-
rotid lymph nodes. There is no obvious prominence of the nasopharyngeal soft tissue. B: Contrast-enhanced axial CT scan at the supraglottic level
demonstrating multiple, homogeneously enlarged cervical lymph nodes bilaterally. The diagnosis is Hodgkin lymphoma.
588 Section IV Problem Solving: Anatomic Regions

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 chapter 19

Spine: Tumors and Infection

Paul E. Kim, Johan W.M. Van Goethem, and Alyssa T. Watanabe

PROBLEMS IN SPINAL TUMOR l­ ocalization information because of relatively poor

IMAGING tissue contrast despite excellent spatial resolution,
and plain radiography significantly provides even
This chapter elucidates a few relatively common prob- less so in both respects. However, in the spine, both
lems encountered in imaging of spinal tumors and are capable of specifying the anatomic compartment
infections. It should be kept in mind that the primary involved if myelographic contrast is used, based on
tasks of diagnostic imaging can be summarized, largely the filling defect pattern of contrast displacement
in order of importance, as follows: (1) detection of the (Figure 19-1, A).
pathological lesion, (2) localization of the lesion, and nn Localization of a lesion in the spine means delinea-
(3) characterization of the lesion to make the most spe- tion of (1) spine segment level involved; (2) which of
cific diagnosis possible. three principal anatomic compartments from which
The first and second issues, detection and localiza- the lesion originated— intramedullary, intradural–
tion of pathology, have been largely resolved since the extramedullary, or extradural (Figure 19-1, B); and
development of cross-sectional imaging, particularly (3) “subcompartment” site of origin (e.g., distinguish-
magnetic resonance imaging (MRI), which is generally ing site of origin among disc, vertebral body, facets,
quite sensitive as well as capable of highly specific ana- etc., for an extradural process).
tomic localization. The third issue, specific diagnosis, nn MRI should be the initial and principal modality
has been elusive in an absolute sense for all but a few of choice for evaluation of tumors of the spine. The
entities; however, ever-evolving technological advance- protocol should include a T2-weighted fat-suppres-
ments over the past several decades have resulted in an sion sequence (fat saturation or inversion recovery)
increasing ability to better characterize lesions and gen- in the sagittal plane as well as contrast-enhanced
erate more specific differential diagnoses with higher T1-weighted images in both sagittal and transverse
probabilistic certainty. planes, with fat suppression.
nn Other considerations:
nn CT, plain x-ray, and angiography: Despite some of
LESION DETECTION AND
LOCALIZATION PROBLEM SOLVING: the limitations noted previously, these modalities
IMAGING MODALITIES often have adjunctive roles in the workup of spinal
tumors. CT, in particular, can show bony detail not
The first task of imaging is detection of pathology, which assessed by MRI. Angiography is reserved for evalu-
is primarily a function of the sensitivity of an imaging ation of vascular lesions.
modality. This is a complex issue that requires distin- nn Advanced imaging techniques: Diffusion tensor
guishing pathology from surrounding normal tissue, imaging (DTI), spectroscopy, and multimodality
which involves spatial resolving capacity when the imaging could play significant roles in lesion char-
pathology is a mass lesion and atomic, molecular, bio- acterization under certain circumstances and are
chemical, physiologic, magnetic, or electrochemical likely to play greater roles in the future. Addition-
properties for non–space-occupying pathologies. The ally, because of recent and ongoing advances in MR
second task is localization of the pathology, a relatively angiography and CT angiography, a viable noninva-
simple function of an imaging modality’s anatomic sive alternative to conventional angiography likely
resolving power, which necessitates high spatial resolu- will be realized in the near future.
tion as well as tissue contrast.
nn MRI versus computed tomography (CT) versus other
DETECTION AND LOCALIZATION
(plain x-ray, nuclear medicine, positron emission TO CHARACTERIZATION AND
tomography): Practically speaking, the best combina- DIFFERENTIAL DIAGNOSIS
tion of sensitivity, spatial localization, and specific-
ity for the spine is afforded by MRI. Although some Lesion Localization for Differential
modalities can surpass MRI in sensitivity for certain
Diagnosis
processes (e.g., technetium-99m [Tc-99m] bone
scintigraphy for detection of bone metastases), spa- The differential diagnostic process should initially begin
tial/contrast resolution and specificity are typically with anatomic localization. A broad anatomically based
much less robust. CT provides generally less precise differential diagnosis is created by identifying the site

589
590 Section IV Problem Solving: Anatomic Regions

Epidural space
Dura mater
Subdural space Internal
Arachnoid mater vertebral
vein
Subarachnoid space
Pia mater
Spinal cord

Dorsal root
Spinal ganglion
Dorsal ramus

Ventral ramus
Intervertebral foramen
Ventral root

Intervertebral Basivertebral Vertebral body

A plexus of veins vein

Figure 19-1 A: Anatomic diagram detailing

meningeal layers of the spinal canal that delin-
eate the epidural, subdural, subarachnoid, and
intramedullary spaces. B: Schematic diagram of
myelographic contrast patterns reflecting lesion Extramedullary Intradural- Intramedullary
space of origin. B Extramedullary

of origin of the lesion as one of three specific anatomic most lesions overlap significantly in appearance with
compartments (Table 19-1): one or more other diagnoses, and specific imaging
nn Intramedullary (Figure 19-2, A) features per se merely promote a higher probability
nn Intradural–extramedullary (Figure 19-2, B) diagnosis rather than an absolute one. Thus, once the
nn Extradural (Figure 19-2, C) anatomic site of the lesion has been determined, the
Caveat: The larger the lesion, the more difficult it may differential diagnostic equation requires consideration
be to identify the site of origin as the mass of the lesion of both clinical information and specific imaging char-
extends into more than one compartment. Consider- acteristics to further narrow the differential diagnosis
ation of more than one anatomic category of differential (Table 19-3):
diagnosis may then be required. nn Clinical information: Demographics, clinical presenta-
tion, and laboratory studies. For example, spinal cord
Narrowing the Differential ependymomas are more common in adults, whereas
Diagnosis: Moving Beyond a Broad astrocytomas are more common in pediatric patients.
nn Specific imaging features that are more characteristic
Anatomically Specific Tabulation
of certain tumor types: Some features are relatively
How specific can imaging be in problem solving? With idiosyncratic to a specific diagnosis and thus have a
the exception of lesions that have nearly pathogno- greater impact on diagnostic probability, for exam-
monic imaging features (so-called “Aunt Minnies” of ple, the classic appearance of a spinal cord heman-
Felson) (Table 19-2 and Figures 19-3 through 19-5), gioblastoma presenting as an enhancing nodule
 Chapter 19 Spine: Tumors and Infection 591

Table 19-1 D
 ifferential Diagnosis of Spinal Lesions by Nuclear medicine: Tc-99m bone scintigraphy and flu-

SECTION IV
nn
Compartment orodeoxyglucose-positron emission tomography typ-
Intradural–Extra- ically do not show increased activity in hemangiomas
Intramedullary medullary Extradural and increased activity with tumor. In addition, Tc-
99m red blood cell pool scans can show radiotracer
Astrocytoma Meningioma Metastasis*
Ependymoma Schwannoma Epidural
accumulation in hemangiomas with low fat content.
nn Confirmation of long-term stability with prior com-
Hemangioblastoma Myxopapillary ­hematoma
Metastasis* ependymoma Epidural abscess parison studies.
Lymphoma* Drop metastasis Schwannoma nn Biopsy: Last resort.
Multiple sclerosis Dural metastasis* Disc ­herniation
Infarct Lymphoma* Lymphoma*
Arteriovenous Arachnoid cyst Chordoma Neoplasm versus Modic 1 Changes
­malformation Cysticercosis Granulomatous*:
Syringomyelia Granulomatous*: Fungal, sarcoid, Modic 1 degenerative end plate changes and vertebral
Rare: Neuronal– Fungal, sarcoid, TB TB metastases demonstrate the same T1, T2, and con-
glial tumors
Granulomatous*:
trast enhancement characteristics: hypointense on T1,
Fungal, sarcoid, TB hypointense on T2, and significant contrast enhance-
ment with gadolinium (Figure 19-8). The distinction
TB, Tuberculosis. usually is readily made by noting the configuration of
*Metastases, lymphoma, and granulomatous processes occur in all three

compartments. the lesion. Modic 1 degenerative end plate changes usu-

ally extend along the vertebral end plate adjacent to a
disc showing varying degrees of degenerative change.
Metastases involving the vertebral bodies are typically
a­ butting the pial surface of the cord with extensive circumscribed geographic lesions. However, rarely a
cord edema (Figure 19-6). Other characteristics may metastasis attains a configuration that mimics Modic 1
have only slightly greater prevalence in one tumor changes along an end plate. Signs of adjacent degenera­
type compared to another. For example, the common tive disc disease may be unhelpful because it is so preva-
diagnostic dilemma of ependymoma versus astrocy- lent in the patient demographic with metastases. The
toma, in which the findings of cyst formation, hetero- problem-solving algorithm should include the following:
geneity, and greater and more homogeneous contrast nn Comparison with prior imaging studies: This is not an
enhancement and blood products can be found in absolute because inflammatory Modic 1 changes can
both tumor types but are somewhat more prevalent develop during a follow-up interval.
in ependymoma than astrocytoma. nn Bone scan: Modic 1 changes do not typically accu-
Caveat: Absolute differentiation frequently is not pos- mulate significant radiotracer activity. In addition,
sible, but differentiating relative probabilities among identification of metastatic lesions elsewhere in the
ependymoma, astrocytoma, metastasis, and heman- skeleton by scintigraphy can mitigate the dilemma.
gioblastoma still may be clinically important because nn Biopsy: Last resort.
treatment differs among these lesions. Ependymoma
may be a surgically resectable lesion, whereas astrocy- Neoplasm versus Infection
toma typically is not. In this regard, advanced imaging
techniques such as DTI may be of additional value. Spinal infections usually begin at the osteocartilaginous
Ependymomas being of ependymal cell origin will end plate and thus typically involve the intervertebral
grow concentrically from the central canal displacing disc. Neoplasms such as metastases do not typically
fiber tracts, whereas astrocytomas typically will have an involve the disc space. However, in some instances, par-
eccentric location and will tend to infiltrate the fiber ticularly when a granulomatous process is in consider-
tracts. ation, neoplastic and inflammatory processes exhibit
similar imaging features: (1) Infection presenting pri-
Common Problems of Differential marily as vertebral osteomyelitis without discitis. This
is particularly the case with tuberculous spondylitis, in
Diagnosis in Spinal Tumor Imaging
which multiple vertebral bodies may be involved with
Neoplasm versus Atypical (Lipid-Poor) sparing of the disc spaces (Figure 19-9). (2) Neoplasm
Hemangioma (Figure 19-7) breaking through the end plate to involve the disc
The typical hemangioma within the vertebral body or ­(Figure 19-9, C). The approach to this problem include
neural arch contains enough fat to be pathognomonic consideration of the following:
on imaging, but a minority, probably less than 15%, nn Clinical factors: Fever, leukocytosis, history of intrave-
lack significant fatty components and thus demon- nous drug use, etc., all are nonspecific associations of
strate high signal intensity on T2-weighted images and infection. Known history of cancer may raise consid-
low signal intensity on T1-weighted images. Contrast eration for metastasis.
enhancement also is common. These findings can be a nn Nonenhancing paraspinous fluid versus enhancing solid
difficult mimic of metastatic disease. The following con- paraspinous mass: Nonenhancing fluid favors infection,
siderations should be made: whereas enhancing solid mass favors neoplasm. Again,
nn Plain x-ray or CT correlation: Classic coarse trabecular this is not absolute because ­granulomatous inflamma-
“corduroy” appearance of hemangioma. tory masses may appear solid, and a pathologic fracture
592 Section IV Problem Solving: Anatomic Regions

A B

C
Figure 19-2 A: Intramedullary process. Sagittal T1-weighted contrast-enhanced image of the cervical spine demonstrating a circumscribed peripher-
ally enhancing, lobulated, cystic lesion arising within the cervical cord. The imaging appearance initially was thought to be most consistent with an epen-
dymoma; this was subsequently believed to be unlikely given a history of very acute onset and rapidly progressive course. Diagnosis was intramedullary
abscess due to Staphylococcus aureus. B: Intradural–extramedullary process. Sagittal T2-weighted image of the thoracic spine demonstrating an intermedi-
ate/low-signal-intensity circumscribed lesion dorsal to the thoracic cord with mass effect. Meningioma. C: Extradural process. Conventional myelogra-
phy (left) and computed tomography myelography (right) demonstrating a lobulated extradural mass extending through the right C2/3 neural foramen
with mass effect on the right side of the thecal sac and cervical cord. This lesion demonstrates the classic “dumbbell” appearance of a schwannoma.

Table 19-2 “Aunt Minnies” of technetium and gallium scans has been reported
to be as high as 94%. Indium white blood cells scans
• Cavernous malformation
• Typical cavernous hemangioma of spine probably are useful only if antibiotic therapy has not
• Disc herniation been administered.
• Modic 2 and 3 changes nn Biopsy: Last resort.

Metastases versus Cellular Marrow

may rarely develop a paraspinous hematoma forming a
Proliferation
nonenhancing fluid collection.
nn Nuclear medicine: Tc-99m bone scans have an accu- Cellular marrow conversion, whether diffuse or hetero-
racy of about 90% in patients with more than 2 days geneous and patchy, appears as diffuse or patchy areas
of symptoms, and gallium scans may be positive even of hypointensity on T1-weighted images and thus can
before the technetium scan. The combined accuracy be concerning for infiltrative metastases. This problem
 Chapter 19 Spine: Tumors and Infection 593

SECTION IV
Figure 19-3 Cavernous malformation. Patient
with multiple cavernous malformations of the
brain and spinal cord. Sagittal T1-weighted (A)
and T2-weighted (B) images of the cervical spine
demonstrating classic appearance of cavernous
malformation and “popcorn”-like appearance
with heterogeneous high and low signal areas
corresponding to variegated blood products
(methemoglobin, hemosiderin, and serous fluid
resulting from multiple prior hemorrhages). In
addition to the cervical cord lesion at C3, a small
pontine lesion (arrowhead) and a large lesion in
A B the cerebellar vermis (small arrows) are seen.

A B C

D E
Figure 19-4 Hemangioma. Typical osseous hemangioma of the vertebral body. Sagittal T1 (A), sagittal T2 (B), sagittal T2 with fat saturation
(C), transverse T2 (D), contrast-enhanced T1 with fat saturation (E) images. Note signal characteristics corresponding to fat within much of the lesion,
demonstrating high signal on T1 and good suppression on both T1 and T2 fat suppression sequences. The suggestion of “corduroy”-type appearance
on sagittal images and dot-like appearance on transverse images are characteristic. Contrast enhancement may be minimal to mild, as shown in E.
594 Section IV Problem Solving: Anatomic Regions

B
Figure 19-5 Modic 2 (A) and Modic 3 (B) changes. Sagittal T1-weighted (left), T2-weighted (middle), and T2 fat suppression (right) images.
A: Modic 2 changes show hyperintense marrow adjacent to the L4–5 end plates on T1-weighted images due to increased fat content that character-
izes Modic 2 changes. Note hyperintensity of these fatty changes on fast spin-echo T2-weighted sequence due to suppression of J-coupling effects
and diffusion-mediated susceptibility dephasing. Fat saturation sequence shows effective fat suppression and hypointensity of Modic 2 fatty mar-
row changes. Note mild Modic 1 changes at the L5–S1 level. B: Modic 3 changes at the L5–S1 level demonstrating hypointensity on all sequences
(arrowheads). This example demonstrates a mixed pattern as well, with small areas of Modic 1 change.

usually is readily resolved by observation of two key fea- all features of pathologic fracture due to underlying
tures (Figure 19-10): neoplasm or infection.
nn Fat-suppressed T2 weighted images: Signal intensity nn Configuration of posterior vertebral fracture margin:
remains relatively hypointense with cellular marrow, A smooth rounded convex posterior vertebral body
whereas metastases are typically hyperintense unless retropulsion is seen with much greater frequency in
osteoblastic. pathologic compression fractures (Figure 19-9, C)
nn Contrast enhancement: Does not occur with cellular than in benign fractures, which typically show a more
marrow. sharply angulated and fractured or retropulsed con-
tour (Figure 19-11). In addition, a well-delineated
Pathologic Fracture versus Benign hypointense fracture line may be identified in a benign
fracture.
Osteoporotic Compression Fracture nn Significant extension of abnormal signal into the pos-
Benign osteoporotic compression fractures are hypoin- terior arch is seen in metastatic disease but not typi-
tense on T1, hyperintense on T2 due to edema, may cally with benign fractures.
have small to moderate amounts of paraspinous mass- nn Signal changes in metastatic disease tend to be some-
like blood/edema/bone fragments (in the case of burst what more homogeneous and diffuse than in benign
fractures), and show significant contrast enhancement, fractures.
 Chapter 19 Spine: Tumors and Infection 595

Table 19-3 Potentially Differentiating Features of Common Spinal Mass Lesions*

SECTION IV
Astrocytoma Age: Children/young adults Imaging:
Gender: M > F = 3:1 � <4 segments
Presentation: � ±Cyst/syrinx
� Slow-onset myelopathy � Hemorrhage uncommon
� May cause painful scoliosis � Low T1, high T2, relatively homogeneous
� +Enhancement: Usually mild/moderate

Ependymoma Age: 35–45 years Imaging:

Gender: F ≥ M � Circumscribed mass with hemorrhagic foci
Presentation: � Low T1, high T2; more inhomogeneous than astrocytoma
� Neck/back pain due to hemorrhagic foci
� Progressive paraparesis, paresthesias � +Enhancement: Usually moderate/intense
Cord metastasis Age: Any with known primary Imaging:
Gender: Depends on primary � Usually <1.5 cm
Presentation: � Always enhances
� Rapidly progressive paraparesis � Spherical or oval
� Pain, hyperesthesia, Brown-Séquard � Key differentiation from hemangioblastoma: Usually not
syndrome subpial
� Syrinx rare
Meningioma Age: Middle age, elderly Imaging:
Gender: F > M = 4:1 � Broad base against dural sac
Presentation: � Intermediate/low signal on both T1 and T2
� Pain � Prominent contrast enhancement ± “dural tail”
� Myelopathy from extrinsic compression:
motor/sensory deficit, gait disturbance
Schwannoma Age: Middle age, 30–60 years Imaging:
Gender: M = F � Classic: “Dumbbell” tumor extending through neural fora-
Presentation: men frequently not seen
� Radicular pain most common � 70% intradural, 15% dumbbell intra/extradural, 15%
completely extradural
� Enlarged neural foramen
� T1: Intermediate/low
T2: Extremely variable—75% hyperintense, remainder mixed
areas of high and low signal, usually peripherally hyperin-
tense and hypointense centrally
� Intense contrast enhancement
� Cysts 40%
� Hemorrhage 10%
Myxopapillary Age: All ages (peak 30–40 years) Imaging:
ependymoma Gender: M > F = 2:1 � Almost exclusively conus, filum terminale, cauda equina
Presentation: � May fill entire thecal sac
� Back pain � Medial pedicle erosion and posterior vertebral body
� Paraparesis ­scalloping
� Lower-extremity radiculopathy � Low T1, high T2; often with heterogeneous foci of
­hemorrhage
� +Enhancement: Intense, homogeneous
*Features listed are typical, not exclusive.
F, Female; M, male.

nn Volume of extraspinous mass: Neoplasm or infection eliminate diffusion-mediated susceptibility dephasing

can result in relatively voluminous paraspinous mass and suppress J-coupling modulation of the echo train.
or fluid. This is rarely the case with benign fractures, Because window width and level are user defined, bright
which typically show only paraspinous edema and/or fatty marrow appears as a hypointense vertebral body
small hematomas. lesion. Because most metastatic neoplasms are hyperin-
tense on T2-weighted images, this high signal can only
“Pseudohypointense” Vertebral be appreciated with a fat suppression sequence such as
Body Lesion in Fast Spin-Echo short tau inversion recovery (STIR) (Table 19-4). Contrast
enhancement is also a differentiating feature, so gadolin-
T2-Weighted Images
ium-enhanced imaging should be performed if necessary
A small pathologic lesion such as a metastasis can be mis- (Figure 19-12). One caveat is blastic metastasis, which
taken for a benign osteoma or enostosis because it appears will be hypointense on all sequences and may not show
hypointense on both T1-weighted and T2-weighted appreciable contrast enhancement if sufficiently ­sclerotic.
images acquired with fast spin-echo technique. This is a In all of the instances discussed in which the problem
common pitfall among trainees due to the hyperintense was metastasis versus other, one should always search
appearance of marrow fat on the fast spin-echo sequence, for the presence of other more typical metastatic lesions.
an effect of multiple 180-degree refocusing pulses, which Although this does not specify the nature of any given
596 Section IV Problem Solving: Anatomic Regions

B C
Figure 19-6 A: Hemangioblastoma. Sagittal T2 (left) and contrast-enhanced T1 (right) images of spinal cord hemangioblastoma with common
characteristic features: relatively small nodular homogeneously enhancing mass, subpial in location, with extensive cord edema out of proportion
to size of the mass. B: Ependymoma. Sagittal T2 (left) and contrast-enhanced T1 (right) images of ependymoma showing more central location of
the lesion and less prominent edema. (Courtesy M. Law.) C: Astrocytoma. T1 contrast-enhanced image showing solid enhancing lesion and large
distal cord syrinx. Note relative homogeneity of the enhancing portion of the mass compared to ependymoma.
 Chapter 19 Spine: Tumors and Infection 597

SECTION IV
A B

C D
Figure 19-7 Atypical hemangioma of the spine. Sagittal T1 (A), sagittal T2 (B), sagittal T2 with fat saturation (C), and transverse T2
(D) images. This lesion demonstrates low lipid content characterized by primarily low signal intensity on T1-weighted and high signal intensity
on T2-weighted images that does not suppress with fat saturation. This lesion continues to demonstrate findings of trabecular coarsening seen as a
dot-like appearance on transverse images (D), but these lesions are often difficult to differentiate from metastases in patients with known cancer.
Technetium-99m–labeled red blood cell studies can be helpful for these atypical lipid-poor lesions.
598 Section IV Problem Solving: Anatomic Regions

A B C

D E

F
Figure 19-8 A–C: Modic type 1 degenerative marrow changes. D–F: Vertebral metastasis. A: Sagittal T1-weighted images showing typical wedge-
shaped area of hypointensity along anteroinferior corner of the L4 vertebral body (arrows). B: T2-weighted image with fat saturation showing
hyperintensity reflecting marrow edema in Modic 1. C: Contrast enhancement after gadolinium administration is common. D–F: Corresponding
image sequences in a patient with metastatic breast carcinoma along the posteroinferior corner of L1 (arrowheads). Note intraspinal extension of
tumor in F (white arrowheads) facilitates distinction from Modic 1 changes.
 Chapter 19 Spine: Tumors and Infection 599

SECTION IV
A B

C
Figure 19-9 A, B: Tuberculous spondylitis. C: Breast carcinoma metastases. Sagittal (A) and transverse (B) T2-weighted images of tuberculous
spondylitis at L3. Characteristic features include sparing of disc spaces, severe vertebral body collapse/deformity, and relatively large paraspi-
nous abscesses (arrows). Similar features are seen in T2-weighted image of metastatic breast carcinoma at L2 in (C). Similar features are seen
in T2-weighted image of metastatic breast carcinoma at L2, but note relatively modest paraspinous soft tissue abnormality consisting of small
amounts of tumor and perhaps hemorrhage, but no large fluid collections. Note additional metastasis at L4, skipping the L3 level, that is also
less characteristic of tuberculous spondylitis, which more often demonstrates contiguous involvement. Note focal breakthrough of the end plate
with disc involvement, a feature more commonly associated with infection (C, white arrow).
600 Section IV Problem Solving: Anatomic Regions

A B C

D E F

Figure 19-10 A–C: Heterogeneous marrow conversion. D–G: Diffuse infiltrative meta-
static breast carcinoma. Sagittal T1-weighted (A) and sagittal T2-weighted (B) images dem-
onstrating patchy, variegated appearance of cellular and fatty marrow elements. C: T2 STIR
image showing suppression of fatty elements and no significant T2 prolongation of cel-
lular elements. Sagittal T1-weighted (D) and sagittal T2-weighted (E) images of infiltrative
metastases showing similar appearance to heterogeneous marrow elements. F: T2 with fat
saturation showing T2 prolongation and hyperintensity of infiltrative metastatic elements.
G G: Contrast-enhanced T1 with fat saturation showing enhancement of metastatic elements
after gadolinium administration.
 Chapter 19 Spine: Tumors and Infection 601

SECTION IV
A B
Figure 19-11 Benign vertebral body fracture. Sagittal T1-weighted (A) and T2-weighted STIR (B) images. Features suggestive of benign fracture
are discrete linear fracture line and irregular, interrupted linear or jagged retropulsion contour (arrows). Note features of pathologic fractures
depicted in Figure 19-9, C, of indistinct fracture line and smoother convex retropulsion contour.

Table 19-4 Vertebral Body Lesions such as elevated myoinositol levels in spinal cord astro-
cytomas compared to multiple sclerosis. As could be
High T1, High Low T1, Low T2, Low T1, Low T2, expected, the primary limitation of the technique is
T2, Low STIR High STIR Low STIR
overcoming the technical limitations associated with
� Hemangioma � Neoplasm � Blastic metastasis the small tissue volumes inherent to the spinal cord.
� Modic 3 (­ metastasis, lymphoma) � Osteoma
� Lipid-poor � Paget disease
­hemangioma � Chronic PROBLEM SOLVING: COMMON
� Osteomyelitis ­osteomyelitis PROBLEMS IN SPINAL INFECTION
� Modic 1 � Bone infarct IMAGING
STIR, Short tau inversion recovery.
As with spinal tumors, the principal role of imaging in
spinal infection is twofold: first, localizing the lesion;
lesion, it does tilt the probability toward a metastatic and second, suggesting a diagnosis or a differential
etiology. It should be relatively uncommon to encoun- diagnosis. Scanning protocols are essentially identical
ter a vertebral body lesion that remains indeterminate to those for tumor imaging, consisting of routine non-
after all imaging considerations are addressed. For these contrast sagittal T1, sagittal T2, sagittal T2 with fat sup-
lesions, biopsy remains the last resort. pression such as STIR or fat saturation, transverse T1
and transverse T2, and contrast-enhanced T1-weighted
PROBLEM SOLVING WITH imaging with fat suppression in the sagittal and trans-
ADVANCED IMAGING: verse planes.
SPECTROSCOPY, DIFFUSION,
DTI, AND TRACTOGRAPHY Localization
DTI of the spinal cord has been studied for a number As with tumor imaging, differential diagnosis is best
of conditions, including trauma, multiple sclerosis, approached using the same anatomic categorization:
and transverse myelitis. With respect to spinal tumor extradural, intradural–extramedullary, and intramedul-
imaging, DTI may have the ability to differentiate lary (Table 19-5).
between ependymoma and metastases or fibrillary
astrocytomas, which are typically infiltrating lesions, PROBLEM: INFECTION VERSUS
whereas ependymomas are typically well-circum- NONINFECTIOUS/INFLAMMATORY
scribed lesions (Figure 19-13). PROCESSES
MR spectroscopy of spinal cord lesions has shown some
promise for differentiating neoplastic and inflammatory Clinical and imaging mimics of infection can make the
or demyelinating lesions. Currently it is an investiga- diagnosis of infection challenging both clinically and
tional tool, but some useful results have been obtained, radiographically. Common presenting symptoms, such
602 Section IV Problem Solving: Anatomic Regions

B
Figure 19-12 A: Sagittal T1 (left) and fast spin-echo T2 (right) images both apparently demonstrating apparently hypointense focal vertebral
lesions. B: T2 STIR image (left), however, more accurately depicting the relatively long T2 relaxivity of the lesions as T2 hyperintensity when sur-
rounding marrow fat is suppressed. Contrast-enhanced T1 with fat saturation (right) showing prominent enhancement of these metastatic lesions.
 Chapter 19 Spine: Tumors and Infection 603

Table 19-5 Infections Considered by Compartment

SECTION IV
Intradural–
Intramedullary Extramedullary Extradural
Viral myelitis Granulomatous: TB, Granulomatous:
Cord abscess fungal TB, fungal
Granulomatous: Spinal meningitis Spondylodiscitis
TB, fungal Parasitic: ­Cysticercosis, and osteomyelitis
echinococcus, Epidural abscess
­schistosomiasis and phlegmon
Facet joint septic
arthritis

TB, Tuberculosis.

Septic Arthritis of Facet Joint versus

Aseptic Facet Synovitis (Figure 19-15)
Mild inflammatory changes normally associated with facet
osteoarthritis is not typically a diagnostic problem. How-
Figure 19-13 Tractography obtained from diffusion tensor imaging ever, inflammatory changes occasionally are so acutely
dataset demonstrating displacement of fibers around the central cord severe that they very closely mimic the appearance of septic
lesion, consistent with ependymoma. Astrocytic tumors are more likely arthritis. Like septic arthritis, the MRI appearance of asep-
to demonstrate disruption or infiltration of fiber tracts rather than dis- tic facet inflammation is characterized by varying amounts
placement. (Courtesy M. Thurnher and M. Law.)
of joint effusion, erosive change, and edema in the subar-
ticular bone and periarticular soft tissues, and prominent
contrast enhancement. The following must be considered:
nn Clinical history: Fever, leukocytosis, clinical setting,
and laboratory studies.
nn Erythrocyte sedimentation rate and C-reactive pro-
tein: C-reactive protein is somewhat more specific
as simple back pain, can occur with or without fever and and generally more helpful.
leukocytosis, which themselves are nonspecific when nn Aspiration: Should be last resort.
present and thus are only indirectly helpful. Likewise, nn Treatment: Facet synovitis can be treated by injection
antecedent history, such as intravenous drug use, raises of corticosteroids, which is contraindicated in case of
suspicion for but does not specify the diagnosis. infection.

Infectious Spondylodiscitis versus Infectious Spondylodiscitis versus

Spondylosis Neuropathic Spondyloarthropathy
The inflammatory component of degenerative disc dis- Like some cases of spondylosis, neuropathic spondylo-
ease is typically manifested on MRI as Modic 1 changes. arthropathy can exhibit all characteristics of infection
Occasionally degenerative changes, particularly when (edema, hyperemia, inflammatory and erosive changes
associated with mixed or persistent inflammatory Modic on plain x-ray and MRI). Diagnostic considerations
1 changes, can be quite severe, showing bony erosion, should include the following:
edema, and inflammation and are virtually indistin- nn Clinical factors: Medical history of a neuropathic con-
guishable from infection (Figure 19-14). Plain radio- dition is significant.
graphs and even nuclear medicine studies may show nn Nuclear medicine: Indium-111 white blood cell scan
findings similar to infection. Problem-solving consider- may be the most reliable in differentiating these enti-
ations are as follows: ties. Tc-99m bone scans are likely to be falsely positive.
nn Vacuum disc: Although common in advanced degen- nn Biopsy: Last resort.
erative disc disease, it is virtually never seen in infec-
tion and is probably the most reassuring imaging Infectious Spondylodiscitis versus
finding in establishing the absence of infection. Dialysis Spondyloarthropathy
nn Erythrocyte sedimentation rate and C-reactive pro-
(Figure 19-16)
tein: These levels should not be significantly elevated
in spondylosis. Dialysis spondyloarthropathy is a virtual mimic of
nn Comparison with prior and follow-up examinations: infection on plain radiographs only. It is not usually a
The time course is typically much shorter than for diagnostic problem for MRI because MRI will be nega-
spondylosis. tive for typical imaging features of infection.
604 Section IV Problem Solving: Anatomic Regions

A B

C
Figure 19-14 Aseptic inflammatory degenerative changes. Sagittal T1 (A), contrast-enhanced T1 with fat saturation (B), and T2 STIR
(C) images. Inflammatory changes associated with degenerative spondylosis may be a close mimic of infection, occasionally with relatively
prominent contrast enhancement and edema. When inflammatory changes are this pronounced, infection should be favored until excluded by
correlation with C-reactive protein and/or biopsy if necessary.
 Chapter 19 Spine: Tumors and Infection 605

SECTION IV
A B

C
Figure 19-15 Inflammatory changes of facet osteoarthritis. Contrast-enhanced T1 with fat saturation (A, B) and T2 with fat saturation
(C) images. Like aseptic inflammatory changes of the disc, inflammatory changes associated with degenerative changes of the facet may some-
times approach the appearance of infection. Bone edema, increased joint space fluid, and periarticular inflammation are all depicted here.

A B
Figure 19-16 Dialysis spondyloarthropathy. A: Plain x-ray film showing loss of disc height and erosive changes at L3–4, mimicking infection.
B: Sagittal T2 STIR magnetic resonance image in a different patient demonstrating chronic changes of end plate sclerosis with no active edema or
inflammatory changes (arrow). (Courtesy D.M. Forrester.)
606 Section IV Problem Solving: Anatomic Regions

A B
Figure 19-17 T2-weighted sagittal (A) and axial (B) images of the thoracic spinal cord. Human immunodeficiency virus (HIV) myelopathy.
Although the appearance may be nonspecific, the tendency for involvement primarily within the posterior and lateral aspects of the cord, as seen
here, is highly suggestive in a patient with known HIV.

A B
Figure 19-18 T2-weighted sagittal (A) and axial (B) images of the thoracic spinal cord. Herpes simplex virus (HSV) myelitis. The appearance is
a nonspecific transverse myelitis, overlapping with other entities such as HIV. In this case, note the more central location of the lesion within the
cord. Additionally, HSV may be necrotizing and demonstrate characteristic involvement of the nerve roots of the cauda equina.

Infectious Myelitis versus some tumors can present without significant cord expan-
Demyelinating Disease or Tumor sion. Diagnostic considerations include the following:
nn Clinical features: Known systemic infection with spe-
Intramedullary pyogenic or granulomatous infection is cific agents tilts diagnostic probability significantly.
extremely rare. Infectious myelitis is usually of viral origin, nn HIV: HIV can present as a myelitis or as a subacute pro-
most commonly human immunodeficiency virus (HIV), cess known as vacuolar myelopathy. Vacuolar myelopathy
herpes simplex virus (HSV), and cytomegalovirus. Typi- is seen as T2 hyperintensity along the dorsal and lateral
cal reported imaging features are not always present, and aspects of the cord (Figure 19-17), reminiscent of myelop-
all entities can present with a nonspecific appearance that athy associated with vitamin B12 deficiency. Because there
could mimic tumor or multiple sclerosis. Cord volume is no inflammatory component in subacute vacuolar
probably is helpful only if a discrete mass is clearly present, myelopathy, no contrast enhancement is seen.
which favors tumor. Mild cord expansion is not a helpful nn Cytomegalovirus and HSV: Although these enti-
distinguishing feature because it can occur in infection and ties can present as a typical myelitis (Figure 19-18),
multiple sclerosis if active inflammation is present, and a ­characteristic presentation is polyradiculitis, with
 Chapter 19 Spine: Tumors and Infection 607

SECTION IV
A B

C
Figure 19-19 Pyogenic spondylodiscitis at L5–S1 in an intravenous drug abuser. T1 (A), T2 STIR (B), and contrast-enhanced T1 (C) images
showing characteristic appearance of end plate/disc space involvement, relatively small epidural/paraspinous abscess formation, and relatively
little bony deformity/collapse compared to tuberculous spondylitis.

prominent enhancement and clumping of nerve roots features that are more characteristic of one over the
of the cauda equina and enhancement of the lepto- other:
meninges of the cord. Because HSV is also encoun- nn Primary involvement of disc space, mild or moder-
tered in HIV patients, differentiation from HIV ate destruction of end plates or vertebral bodies, and
myelopathy by imaging may be made when contrast variable but usually small- to moderate-sized paraspi-
enhancement, necrosis, and/or hemorrhage is seen, nous fluid collections (abscesses), fever, leukocytosis,
in addition to nerve root clumping and enhancement. and history of intravenous drug abuse are more typi-
cal of pyogenic spondylodiscitis (Figure 19-19).
nn Relative sparing of the disc spaces with extensive
Infectious Spondylodiscitis
vertebral body involvement including severe verte-
Suspected Radiographically
bral body collapse and deformity, large paraspinous
Determination of Type of Infection fluid collections (“cold” abscesses), clinical presen-
Once infection is suspected radiographically, the next tation primarily of back pain without significant
diagnostic consideration is whether the infection is fever and leukocytosis favor tuberculous spondylitis
pyogenic or granulomatous. Each entity demonstrates (Figure 19-20).
608 Section IV Problem Solving: Anatomic Regions

A B

C
Figure 19-20 Typical features of tuberculous (TB) spondylitis. Sagittal T1 (A), T2 STIR (B), and axial T2-weighted (C) images demonstrating
many hallmarks of TB spondylitis: relative sparing of discs; subligamentous spread to multiple contiguous levels (white arrows); extensive vertebral
body destruction and deformity, including gibbus deformity; and large paraspinous “cold abscesses” (black arrows).
 Chapter 19 Spine: Tumors and Infection 609

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proton magnetic resonance spectroscopy of the human cervical spinal cord
An HS, Seldomridge JA. Spinal infections: diagnostic tests and imaging studies. at 3 Tesla. Magn Reson Med. 2007;57(1):160–3.
Clin Orthop Relat Res. 2006;444:27-33 Modic MT, Feiglin DH, Piraino DW, et al. Vertebral osteomyelitis: Assessment
Casey B. AuntMinnieTV: What’s an Aunt Minnie? Interview with Dr. Maurice using MR. Radiology. 1985;157:157-166.
Reeder. AuntMinnie.com, 2004. www.youtube.com/watch?v=FsCcnkkMovU Modic MT, Steinberg PM, Ross JS, Masaryk TJ, Carter JR. Degenerative disk
Czervionke LF, Fenton DS. Fat-saturated MR imaging in the detection of disease: assessment of changes in vertebral body marrow with MR imaging.
inflammatory facet arthropathy (facet synovitis) in the lumbar spine. Pain Radiology. 1988;166:193-199.
Med. 2008;9(4):400–6. Nakajima H, Furutama D, Kimura F, et al. Herpes simplex virus myelitis:
Choi YY, Seong JY, Yang SO, Lee SR, Cho S. Tc-99m RBC SPECT demonstrating clinical manifestations and diagnosis by the polymerase chain reaction
vertebral hemangioma. Clin Nucl Med. 1998;23(9):632–4. method. Eur Neurol. 1998;39:163-167.
Cuénod CA, Laredo J-D, Chevret S, et al. Acute vertebral collapse due to Norris S, Ehrlich MG, McKusick K. Early diagnosis of disk space infection with
osteoporosis or malignance: appearance on unenhanced and gadolinium- 67 Ga in an experimental model. Clin Orthop. 1979;144:293-298.
enhanced MR images. Radiology. 1996;199(2):541-549. Sartoretti-Schefer S, Blattler T, Wichmann W. Spinal MRI in vacuolar
D’Aprile P, Tarantino A, Jinkins JR, Brindicci D. The value of fat saturation myelopathy, and correlation with histopathological findings. Neuroradiology.
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Radiol. 2007;17(2):523–31. value of computed tomography in the diagnosis of low back pain. A review
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Spine Radiology 2007 Annual Symposium, Marco Island, Florida, February Thrush A, Enzmann D. MR imaging of infectious spondylitis. AJNR Am J
22-25, 2007. Neuroradiol. 1990;11(6):1171–80.
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2004;25(6):461–73. of the spine and spinal cord in 55 patients with AIDS. Neuroradiology.
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 chapter 20

Spine and Lower Back Pain

Johan W.M. Van Goethem, Paul E. Kim, and Alyssa T. Watanabe

Cauda Equina Syndrome

LOW BACK PAIN
Cauda equina syndrome is typically characterized by
Low back pain (LBP) is a common complaint in West- LBP, sciatica, lower-extremity sensorimotor loss, and
ern society, with a prevalence ranging from 5% to 65% bowel and bladder dysfunction. Classically, the full-
and a mean of 18.7%. Estimates of total costs per capita blown syndrome includes urinary retention, saddle
per year for LBP in Europe range from €116 to €399. anesthesia of the perineum, bilateral lower-extremity
Most occurrences of LBP are believed to be benign and pain, numbness, and weakness. The pathophysiology
self-limiting. The real challenge to the clinician is to remains unclear but may be related to damage to the
distinguish serious spinal pathology or nerve root pain nerve roots composing the cauda equina, usually from
from nonspecific LBP. Clinical, anamnestic, and labora- direct mechanical compression but also less frequently
tory findings may help in differentiating these causes. from venous congestion and/or ischemia. Early diag-
In cases where either serious spinal pathology and/or nosis is often challenging because the initial signs and
treatable causes of LBP are not ruled out, imaging can symptoms frequently are subtle. Because treatment is
be very valuable. urgent surgical decompression of the spinal canal, imag-
ing is a cornerstone in the workup of these patients. Fre-
Low Back Pain quent causes of cauda equina syndrome include disc
herniation, trauma, and/or vertebral metastasis with
Acute Low Back Pain secondary spinal stenosis and compression of the cauda
Acute LBP is limited to 6 to 12 weeks in duration before it equina. Because of the diversity of the potential causes
is considered chronic. In general, imaging is not recom- of compression and the uncertain thoracolumbar level
mended for first episodes of acute LBP without leg pain of compression, magnetic resonance (MR) is the pre-
unless specific findings are present. These specific find- ferred imaging technique for cauda equina syndrome.
ings, called red flags, are indicators of possible underly-
ing serious disease. In acute LBP, these findings include Infection
trauma, cauda equina syndrome, progressive neurologic Spinal infections are covered more extensively in Chapter
deficit, infection, and/or malignancy. In chronic LBP, 19. Spinal infections can occur in the bone of the vertebral
these red flags are more elaborate. column, the intervertebral disc space, the spinal canal, or
any combination of these. Spinal infections are most fre-
Trauma quently caused by bacteria and cause significant LBP.
Spinal trauma is covered more extensively in Chapter
13. In summary, in acute traumatic LBP, clinical crite- Aspecific Acute LBP
ria allow reliable patient triage of those who need or From 80% to 90% of cases of LBP are considered aspecific
do not need be imaged. Two large prospective studies because the anatomic origin of the pain remains elusive.
on C-spine trauma determined simple clinical criteria Intervertebral discs, facet and sacroiliac joints, and, to a
that can be used to exclude fractures safely without lesser degree, ligaments and muscles all can play a role
imaging in many low-risk subjects. The recommenda- as pain generator in acute LBP. It is usually impossible
tions of the older National Emergency X-Radiography to assign acute LBP to a structural or functional correlate
Utilization Study (NEXUS) are largely surpassed by the using anamnestic, clinical, or imaging findings.
newer Canadian C-Spine Rule study. The criteria of the Intervertebral disc pathology is thought to be one of the
Canadian C-Spine Rule are listed in Table 13-1. In sub- causative factors of LBP. Studies demonstrating innerva-
jects in whom imaging is indicated and are high-risk tion to the intervertebral disc provide evidence that may
subjects, cost-effectiveness analysis suggests that com- account for instances of discogenic LBP. Innervation of
puted tomography (CT) is the preferred initial strat- the inner disc was observed only in painful discs, not in
egy. To appropriately identify these high-risk subjects, normal control discs. Based on these observations, nerve
the Harborview criteria are very useful. Compared with ingrowth into the inner disc may be a cause of nonspe-
radiography, the higher short-term costs of CT are coun- cific discogenic LBP. Magnetic resonance imaging (MRI)
terbalanced by the decreased need for further imaging in findings that correlate with painful discs on discogra-
patients without injury and the increased sensitivity for phy are those typical for disc degeneration, mainly sig-
fractures or other significant lesions. nal loss of the disc on T2-weighted imaging (T2-WI),

610
 Chapter 20 Spine and Lower Back Pain 611

Table 20-1 Modic Changes According to Magnetic

SECTION IV
Resonance Signal Intensity Changes of Adjacent
­Vertebral End Plates
Modic
­Classification T1–SI T2–SI Represents
1 – + Vascularized bone
marrow and/or
edema
2 + + Proliferation of
fatty tissue
3 – – Sclerotic bone

10%, with Modic type 1 changes being very uncommon

(<0.1%). The prevalence of Modic changes increases
with age. In patients with LBP, the prevalence of Modic
changes is reported between 20% and 60%. Modic
changes are a common finding in patients with nonspe-
cific LBP (median prevalence 43%) and are less common
in nonclinical populations (median prevalence 6%).
Modic changes are associated with LBP, with estimated
Figure 20-1 Tear in the annulus fibrosus (now referred to as hyperin- odds ratios between 2.0 and 19.9. There is no statistical
tensity zones). Tears in the annulus fibrosus are best seen on T2-weighted difference in the association between LBP and the type
imaging where they appear as bright zones in the intervertebral disc. of Modic changes. The reasons why Modic changes are
They are also noted on T1-weighted imaging after gadolinium because associated with LBP are not known. The lumbar verte-
they tend to enhance. Tears are classified as radial, transverse, or con-
centric, involving one or many layers of the annular lamellae. bral end plate contains immunoreactive nerves, and it
has been reported that an increased number of tumor
necrosis factor immunoreactive nerve cells and fibers
but also loss of disc height, presence of a hyperintensity are present in end plates that have Modic changes, espe-
zone, and bone marrow changes. cially type 1 changes.
The hyperintensity zone is a localized region of high
signal intensity on T2-WI at the midline within the Chronic LBP
posterior annulus fibrosus. Histopathologically these Although the differential diagnosis is extensive, most
lesions represent replacement of the normal lamellar cases of chronic LBP have biomechanical causes. Diag-
structure by a disorganized, vascularized granulation nostic imaging should be ordered only when necessary
tissue consisting of small round cells, fibroblasts, and because of the high incidence of radiologic abnormali-
newly formed blood vessels around tears that extend ties in asymptomatic persons. Therefore, history and
from the nucleus pulposus to the outer region of the physical examination are important in distinguish-
annulus fibrosus. Originally the presence of a hyperin- ing potential causes and identifying red flags for more
tensity zone was strongly correlated with a painful disc serious conditions. The presence of red flags calls for
on discography. This correlation was confirmed in mul- imaging, and an overview is given in Figure 20-4. Some
tiple later studies but also was questioned in a few other conditions (listed in bottom half of Figure 20-4) war-
studies. In general, the association between an annular rant prompt MRI of the spine.
tear on MRI and LBP is unclear (Figure 20-1).
Modic changes in the vertebral end plates adjoining Known Malignancy and Systemic Disease
a degenerative disc were first described in 1988 (Table The spine is recognized as the most common site for
20-1). Modic et al. reported two types of changes: Modic bony metastases in patients with known malignancy
type 1 (Figure 20-2), histopathologically corresponding and are found in 10% of patients with malignant neo-
to vascular granulation tissue, and Modic type 2, repre- plasms. Suspicion for vertebral metastatic disease is
senting fatty degeneration (Figure 20-3). Modic type 3 especially high in these patients with (chronic) LBP.
changes representing bone sclerosis were added later Spinal metastases most often originate from carcinomas
(Figure 20-3). Some groups also use the term Modic of the breast (21%), lung (14%), prostate (7.5%), kid-
type 0 for normal vertebral bone marrow. Modic type 1 ney (5%), and gastrointestinal tract (5%). These tumors
changes are dark on T1-WI and bright on T2-WI, Modic generally involve the bones of the vertebrae or the sur-
type 2 changes are bright on both sequences, and Modic face of the spinal cord, and less than 5% of all meta-
type 3 changes are dark on both sequences. static spine tumors are intradural (either intramedullary
In general, Modic type 2 changes are the most frequent or extramedullary). The sensitivity for detecting, and
(60%–90%), followed by type 1 changes (10%–40%). especially for ruling out, vertebral metastases is much
Type 3 changes are rare. Mixed types are recognized but higher for MRI than for plain film, warranting MRI as
are also less frequent. The prevalence of Modic changes a first examination technique in these patients. MRI is
in asymptomatic patients is reported between 0% and also more accurate than radionuclide bone scan and is
612 Section IV Problem Solving: Anatomic Regions

A B
Figure 20-2 Modic type 1 changes. Reactive vertebral body modifications associated with disc inflammation and degenerative disc disease as
seen on magnetic resonance images. Type 1 refers to decreased signal intensity on T1-weighted spin-echo images (A) and increased signal intensity
on T2-weighted images (B), indicating bone marrow edema associated with acute or subacute inflammatory changes.

A B
Figure 20-3 Modic type 2 and type 3 changes. Types 2 and 3 indicate chronic changes. Type 2 refers to increased signal intensity on T1-weighted
image (A, level L4–5) and isointense or increased signal intensity on T2-weighted image (B, level L4–5), indicating replacement of normal bone
marrow by fat. Type 3 refers to decreased signal intensity on both T1-weighted and T2-weighted images (A and B, level L5–S1), indicating reactive
osteosclerosis classification of lumbar disc abnormalities.

advocated as a screening tool in patients with a high risk corresponding to the time it takes for water and fat pro-
of metastatic disease in breast, lung, and prostate carci- tons to move exactly 180 degrees out of phase. This
noma. time depends on the field strength of the magnet and is
When screening for vertebral metastases, sagittal (T) approximately 7 ms for a 1.5-T imager and 11 ms for a
spin-echo (SE) T1-WI and T2-WI should be performed 1.0-T machine. In the normal adult human, the medul-
(Figure 20-5). In addition, a sagittal gradient-recalled lary bone of the vertebral bodies contains approximately
echo (GRE) (so-called out-of-phase) sequence can be equal amounts of water and fat protons. In out-of-phase
used. This is a sequence with a specific echo time (TE) conditions, the signal of both will cancel out, leaving
 Chapter 20 Spine and Lower Back Pain 613

the vertebrae completely black. In the case of vertebral Structural Malformation: Scoliosis

SECTION IV
pathology, the signal will increase, and, as such, verte- The normal human spine has a series of curves in the
bral metastases (or other lesions) will clearly stand out. sagittal plane, including a cervical lordosis that averages
If a metastasis extends into the spinal canal or neural (depending on the endpoints) 20 to 50 degrees (C2–7)
foramen, additional axial T1-WI after gadolinium injec- or 30 to 70 degrees (C1–T1), a thoracic kyphosis averag-
tion should be performed. ing 30 to 35 degrees (T5–T12), and a lumbar lordosis
Besides metastatic disease, many other systemic dis- averaging 50 to 60 degrees (T12–S1). The normal cervi-
eases may affect the spine, including multiple myeloma, cal lordosis is a circular arc. In the frontal plane, the nor-
lymphoma, and leukemia. mal load-bearing spine is straight. Scoliosis is defined as
a deviation from the midline in a frontal plane. A small
deviation (<10 degrees) is sometimes called spinal asym-
metry, whereas “true” scoliosis has a deviation 10 degrees
Red flags or greater. This deviation is accompanied by a rotation
that is maximal at the apex of the curve. Imaging in sco-
• structural malformation liosis is very important. Most cases of scoliosis are idio-
Plain film pathic, and imaging is used routinely for monitoring the
• start <20 or >55 years changes of the deformity that take place during growth.
In addition, imaging is crucial in determining the under-
• steroid use
lying etiology in nonidiopathic cases of scoliosis. Finally,
imaging is used in preoperative and postoperative moni-
• non-mechanical pain (not better after toring. Most frequently scoliosis is idiopathic (80%).
rest and/or progressive) Substantial research efforts have identified several fac-
tors that contribute to the development of idiopathic
• known malignancy-systemic disease-
weight loss-HIV scoliosis. Genetic factors are a potential etiologic com-
ponent in the development of scoliosis. Studies suggest
• sphincter or gait disturbances a multigene dominant inheritance pattern with variable
MR phenotypic expression, although no specific genes have
• serious or progressive weakness
been identified so far. Family members of affected indi-
Figure 20-4 Red flags in chronic low back pain. The presence of any viduals have an increased incidence of scoliosis. Studies
of these findings warrants further investigation with imaging. Depend- in families with twins have identified 73% to 92% con-
ing on the possible underlying cause, a gradient among these red flags cordance in monozygotic twins and only 36% to 63%
exists in which plain film imaging can be performed before deciding
whether further imaging (magnetic resonance [MR] imaging and/or
concordance in dizygotic twins. The prevalence of sco-
computed tomography) is necessary in the first group and MR imaging liosis increases seven times in individuals with affected
is mandatory in the last group. HIV, Human immunodeficiency virus. siblings and three times in those with affected parents.

A B C D
Figure 20-5 Vertebral metastases. A: Sagittal T1-weighted imaging (T1-WI) without gadolinium usually shows the most contrast between nor-
mal bone marrow and invasive pathology such as metastatic disease. B: Lesions are clearly less conspicuous on T2-WI because of high signal of
fat containing bone marrow and equally high signal of lesions. C: This is partly overcome with fat-saturated T2-WI. D: Note hypointense bone
marrow lesions on T1-WI (such as most metastases) become less conspicuous after administration of gadolinium because enhancement of lesions
renders them isointense to normal marrow.
614 Section IV Problem Solving: Anatomic Regions

There is no difference in the prevalence of back pain Radicular Pain

or mortality between patients with untreated adoles- Acute lumbar disc herniations are the most common
cent idiopathic scoliosis and the general population. cause of acute radicular leg pain. After excluding emer-
Patients with mild idiopathic scoliosis (<25 degrees) gent causes, such as cauda equina syndrome, epidural
usually have no or only very little discomfort. Car- abscess, fracture, and malignancy, a 6-week trial of con-
diopulmonary complications are almost exclusively servative management is indicated. Patients should be
seen in early-onset scoliosis (<5 years old). Patients advised to stay active. If symptoms persist after 6 weeks
presenting with severe pain, neurologic symptoms, or or neurologic function worsens, imaging and invasive
rapidly progressing scoliosis require thorough further procedures may be considered. Most patients with lum-
examination. bar disc herniations improve over 6 weeks.
The ideal imaging modality for screening in sco- If a disc herniation is identified that correlates with
liosis is the upright posteroanterior radiograph of the physical findings, surgical discectomy may improve
entire spine (Figure 20-6). The head and pelvis should symptoms more quickly than continued conservative
be on the same film. The patient must be standing, management. Epidural steroid injections can also pro-
but in young patients or patients with severe neuro- vide short-term relief.
muscular disorders a sitting or even supine radiograph Herniated discs are more easily detected with MRI
may be the only possibility. In general, no attempt than with CT for a number of reasons (Figure 20-7).
should be made to equalize differences in leg length. First, MRI allows visualization of the complete lum-
A lateral film is not required as part of the screen- bar (or cervical or thoracic) spine in one examination.
ing examination. Radiographic techniques should be Second, sagittal images also depict the spinal canal in
used to minimize radiation of sensitive organs (most between intervertebral disc spaces. It is not unusual
importantly breast, thyroid, ovaries, bone marrow for a disc fragment to migrate (or extend) into the
and lens. It is imperative that radiation-lowering tech- area behind the vertebral body (Figure 20-8). Some of
niques are used judiciously to minimize the radiation these migrated discs can be missed on CT if axial slices
burden. are limited to the intervertebral disc spaces examined.
Finally, intrinsic tissue contrast is usually better on MR.
Leg Pain The cervicothoracic and/or lumbosacral regions can be
particularly hard to assess on CT due to beam harden-
Leg pain can occur following a particular dermatome, ing, especially in larger patients.
also called radicular pain or sciatica, or in an aspecific The terms used to describe or classify bulging or her-
region, known as nonradicular pain. niated discs are somewhat ambiguous and sometimes
misused. The nomenclature project initiated by the
American Society of Spine Radiology has found wide
acceptance among radiologists, clinicians, and surgeons.
In this nomenclature, herniation is defined as a local-
ized displacement of disc material beyond the limits of
the intervertebral disc space. The disc material may be
nucleus, cartilage, fragmented apophyseal bone, annu-
lar tissue, or any combination thereof. The term localized
contrasts to generalized, the latter being arbitrarily defined
as greater than 50% (180 degrees) of the periphery of
the disc. Localized displacement in the axial (horizon-
tal) plane can be “focal,” signifying less than 25% of the
disc circumference, or “broad based,” meaning between
25% and 50% of the disc circumference. The presence
of disc tissue “circumferentially” (50%–100%) beyond
the edges of the ring apophyses may be called bulging
and is not considered a form of herniation, nor are dif-
fuse adaptive alterations of the disc contour secondary
to adjacent deformity, as may be present in severe sco-
liosis or spondylolisthesis. Herniated discs may take the
form of protrusion or extrusion, based on the shape of
the displaced material. Protrusion is present if the great-
est distance, in any plane, between the edges of the disc
material beyond the disc space is less than the distance
Figure 20-6 Scoliosis. An upright posteroanterior film of the com- between the edges of the base in the same plane. The
plete spine that includes the head and pelvis is the standard screening base is defined as the cross-sectional area of disc material
examination in the diagnosis and follow-up of scoliosis. Meticulous at the outer margin of the disc space of origin, where disc
radiation dose reduction is important because these patients usually material displaced beyond the disc space is continuous
are adolescents who have highly radiation-sensitive organs, including
the breasts, thyroid, and reproductive organs. Patients having scoliosis with disc material within the disc space. In the cranio-
with a Cobb angle less than 25 degrees do not have a significantly caudal direction, the length of the base cannot exceed,
higher prevalence of back pain. by definition, the height of the intervertebral space.
 Chapter 20 Spine and Lower Back Pain 615

SECTION IV
A B

C D
Figure 20-7 Lumbar disc herniation-type extrusion. Sagittal T1-weighted (A) and T2-weighted (B) imaging and axial T1-weighted (C) and
T2-weighted (D) imaging of an L4–5 disc herniation. A disc herniation is defined as a localized displacement of disc material beyond the limits of
the intervertebral disc space. Herniated discs may take the form of protrusion or extrusion, based on the shape of the displaced material. Protru-
sion is present if the greatest distance, in any plane, between the edges of the disc material beyond the disc space is less than the distance between
the edges of the base, in the same plane. The base is defined as the cross-sectional area of disc material at the outer margin of the disc space of
origin, where disc material displaced beyond the disc space is continuous with disc material within the disc space. In the craniocaudal direction,
the length of the base cannot exceed, by definition, the height of the intervertebral space. Extrusion is present when, in at least one plane, any
one distance between the edges of the disc material beyond the disc space is greater than the distance between the edges of the base, or when no
continuity exists between the disc material beyond the disc space and that within the disc space.

Extrusion is present when, in at least one plane, any one protrusion on axial sections and an extrusion on sagittal
distance between the edges of the disc material beyond sections, in which cases the displacement should be con-
the disc space is greater than the distance between the sidered an extrusion. Herniated discs in the craniocaudal
edges of the base in the same plane, or when no continu- (vertical) direction through a break in the vertebral body
ity exists between the disc material beyond the disc space end plate are referred to as intravertebral herniations. Disc
and that within the disc space (Figure 20-7). Extrusion herniations may be further specifically described as con-
may be further specified as sequestration, if the displaced tained, if the displaced portion is covered by the outer
disc material has completely lost all continuity with the annulus, or uncontained, if any such covering is absent.
parent disc (Figure 20-8). The term migration may be Displaced disc tissues may also be described by location,
used to signify displacement of disc material away from volume, and content.
the site of extrusion, regardless of whether or not it is Chronic radicular pain can be caused by a disc herni-
sequestrated. Because posteriorly displaced disc mate- ation, but vertebral osteophytic spurs and degenerative
rial is often constrained by the posterior longitudinal foraminal stenosis are other important causes of nerve
ligament, images may portray a disc displacement as a root irritation. Foraminal nerve root entrapment is best
616 Section IV Problem Solving: Anatomic Regions

A B

C D
Figure 20-8 Lumbar disc herniation-type extrusion, sequestration and migration. Sagittal T1-weighted (A) and T2-weighted (B) imaging and
axial T1-weighted imaging before (C) and after administration of gadolinium (D) of a surgically proven L3–4 disc herniation. Extrusion may be
further specified as sequestration if the displaced disc material has lost completely any continuity with the parent disc. The term migration may be
used to signify displacement of disc material away from the site of extrusion, whether sequestrated or not.

visualized on MRI where the high contrast between fat and perispinal muscular changes. MRI is the most sensi-
tissue and the nerve root sheath is of great help (Figure tive imaging method for evaluation of spinal degenera-
20-9). Usually a combination of hypertrophic degen- tive pathology, even in the initial stages of the disease.
erative facets with osteophytic spurs posteriorly and T2-weighted sequences with fat saturation and, when
vertebral osteophytes and/or disc herniation anteriorly indicated, contrast-enhanced T1-WI with fat satura-
diminishes the anteroposterior diameter of the foramen. tion permit visualization of degenerative–inflammatory
Foraminal height is lessened by degenerative disc disease changes of the posterior elements of the lumbar spine
and subsequent disc height loss. Whenever the normal that in most cases would have been overlooked with
rounded (oval) appearance of the nerve root sheath is conventional non–fat-suppressed imaging.
lost in combination with loss of the surrounding fat tis- Pathology of the vertebral column, such as spondy-
sue, nerve root compression should be considered. losis, (osteoporotic) fractures, and vertebral metastases,
are other possible causes of irradiating nonradicular spi-
Nonradicular Pain nal pain.
Nonradicular LBP may arise from changes of the poste-
rior elements/perispinal tissues of the lumbar spine (i.e., NEUROGENIC CLAUDICATION
the “posterior vertebral compartment”). This includes
facet joint pathology (Figure 20-10) (e.g., osteoarthritis, Contrary to intermittent claudication, which is caused
joint effusion, synovitis, synovial cysts), spinal/perispi- by poor blood circulation, neurogenic claudication is
nal ligamentous degenerative–inflammatory changes due to spinal cord or spinal nerve root compression
 Chapter 20 Spine and Lower Back Pain 617

SECTION IV
A B

A B
Figure 20-9 Foraminal stenosis by degenerative disease with intra-
foraminal facet joint cyst. Foraminal nerve root irritation/compression
is fairly frequent in degenerative spinal disease. Usually a combination
of disc degeneration with lessened foraminal height and facet degen-
eration with osteophytic spurs and/or hypertrophic changes causes
the narrowing. In this case, an intraforaminal degenerative facet joint
cyst further com­presses the exiting nerve root. The cyst is difficult
to distinguish on T1-weighted imaging (A) but is clearly visible on
T2-weighted imaging (B).

C
Figure 20-11 Spinal stenosis. Sagittal T1-weighted (A) and
T2-weighted (B) imaging and axial T1-weighted imaging (C). Degen-
erative spinal stenosis mainly due to degenerative facet disease with
anterolisthesis but also due to disc herniation. In severe stenosis, the
nerve roots of the cauda equina can be pulled through the stenosis
in flexion but remain above in a neutral position, causing the typi-
cal image of curly nerve roots above the stenosis known as redundant
nerve roots.

and/or spinal stenosis. This compression most often

occurs in the lumbar portion of the spine and clinically
presents with pain and numbness in the low back, legs,
and buttocks after walking or extension of the lumbar
spine (Figure 20-11). The symptoms associated with
lumbar spinal stenosis are usually relieved with flexion
of the lower back. Spinal stenosis may be the result of
narrowing of the spinal canal, which is the more com-
mon cause of neurogenic claudication, but sometimes
Figure 20-10 Degenerative facet disease. Computed tomographic multilevel lateral recess and/or foraminal stenosis pro-
image nicely depicting the different aspects of degenerative facet dis- duces comparable symptoms.
ease: narrowing of the joint space, formation of osteophytic spurs,
subchondral bone sclerosis, and subchondral cyst formation (arrows).
Several imaging criteria in diagnosing spinal steno-
Degenerative facet disease not only causes low back pain but also can sis have been established. Spinal stenosis can be eval-
be responsible for irradiating nonradicular leg pain. uated by measuring the diameter of the spinal canal
618 Section IV Problem Solving: Anatomic Regions

or by ­looking at the relative space that is available for alone can be impossible. Severe postoperative inflam-
the nerves of the cauda equina. In radiologic evalua- matory changes without infection is also sometimes
tion of spinal stenosis, remember that not all patients called sterile spondylodiscitis.
with a narrow spinal canal have neurogenic claudica- Comparably, diagnosing postoperative spondylodis-
tion. Also keep in mind that the diameter of the spi- citis and differentiating it from the normal inflamma-
nal canal usually is maximal during CT and/or MR tory postoperative changes can be very difficult, if not
examinations when the patient is in supine unloaded impossible, in some cases. Postoperative spondylodis-
position. In performing absolute measurements of the citis occurs in about 0.4% of patients in the cervical
spinal canal, 10 mm is the accepted minimal antero- spine and between 0.1% to 3% in the lumbar spine.
posterior diameter of the dural sac at the lumbar level. Although the incidence of postoperative infection may
Any measurement less than 10 mm is interpreted as be progressively decreasing due to better technical and
a spinal stenosis. Looking at the relative space avail- prophylactic measures, it has not been completely
able, absence of cerebrospinal fluid (CSF) around the eliminated. The infection is mostly due to direct intra-
roots of the cauda equina (i.e., only nerve roots are operative contamination, although a preoperative or
seen in the dural sac and no fluid is detected) is a fre- perioperative infection at another anatomic site or an
quently used criterion to diagnose relevant spinal ste- underlying immunocompromising condition can also
nosis on imaging, both cross-sectional and on plain predispose. The organisms involved are usually Staph-
film myelography. ylococcus epidermidis or Staphylococcus aureus. Patients
with postoperative spondylodiscitis usually present
POSTOPERATIVE LUMBAR SPINE with severe recurrent LBP 7 to 28 days after surgery.
Imaging is mostly important in excluding a suspected
Postoperative Acute Recurring Pain postoperative spondylodiscitis. Patients without high
signal of the intervertebral space on T2-WI or without
Postoperative Acute Recurring LBP Modic type 1-like changes in the vertebral bodies of the
Acute recurring LBP in the immediate postoperative affected level or without enhancement of at least part
period should raise the suspicion of a surgical com- of the intervertebral space and/or vertebral bodies are
plication, including bleeding, malplacement or disen- very unlikely to have postoperative spondylodiscitis. In
gagement of instrumentation, and severe inflammatory general, the diagnosis of postoperative spondylodiscitis
reaction. Severe recurring pain several days to a few is based on a combination of clinical, laboratory, and
weeks after surgery is typical for a postoperative infec- imaging findings (Figure 20-13).
tion (e.g., postoperative spondylodiscitis).
Plain film is an appropriate technique to check the Postoperative Acute Recurring Leg Pain
placement and integrity of spinal instrumentation Acute recurring leg pain, if radicular, is in principle due
immediately after surgery. Misplacement of pedicle to nerve root irritation. In almost all cases, MRI is the
screws, especially in the upper lumbar or thoracic level, imaging technique of choice in these patients.
is sometimes easier appreciated on CT. For all other MRI in the early postoperative phase (first 6 weeks)
surgical complications, including hemorrhage, inflam- in asymptomatic patients shows a residual disc hernia-
mation, and infection, MR is the imaging technique of tion with mass effect in about 1 of 4 cases. This number
choice. reduces significantly 6 months after surgery. Diagnosing
Malplacement of pedicle screws is not always clinically a clinically significant early recurrent disc herniation is
significant. Only screws (or cages) that encroach on the therefore very challenging. On the other hand, abnor-
spinal canal, and especially the neuroforamen, and cor- mal postoperative findings, including hemorrhage and
relate with the clinical picture by their position relative failure or misplacement of instrumentation, with nerve
to the possibly affected neural structures are significant root irritation are easier to diagnose.
in acute recurring leg pain. Pedicle screws that penetrate The normal epidural fat in the lumbar spine is very
the anterior vertebral border, especially at the S1 level, bright on T1-WI and contrasts well with the dural sac
are usually not clinically significant and even are some- and the adjacent normal or pathologic intervertebral
times placed there on purpose to have better screw fixa- disc. This explains why axial T1-WI is of high value in
tion (bicortical placement). the lumbar region. Furthermore, the high signal of nor-
Hemorrhage and/or fluid in the posterior soft tissues mal epidural fat contrasts well with postoperative epi-
along the surgical tract in the first days after surgery is a dural fibrosis, which is dark. On unenhanced images
normal finding, unless the mass effect causes significant immediately after surgery, postdiscectomy changes can
compression of surrounding structures (Figure 20-12). mimic the preoperative appearance of disc herniation in
Although uncommon, occurring in less than 1% of the epidural space because of disruption of the annulus
patients, symptomatic postoperative hemorrhage typi- fibrosus and edema of the epidural tissues. These render
cally presents hours to days following the spinal surgical the outline of the dural sac and the posterior margin of
procedure. the intervertebral disc and may efface the anterior bor-
Inflammation depicted by Modic type 1-like changes der of the thecal sac. Additional axial T1-WI after intra-
in the vertebral bodies and/or enhancement in the venous gadolinium are mandatory in patients who have
intervertebral and epidural space is normal in the first undergone prior disc surgery. Use of contrast medium is
6 months after surgery. Separating abnormal inflam- important in differentiating scar tissue (fibrosis) from
mation and normal postoperative changes on imaging recurrent disc herniation, which is essential because the
 Chapter 20 Spine and Lower Back Pain 619

SECTION IV
A B

C D
Figure 20-12 Postoperative hemorrhage in same patient as shown in Figure 20-15, 1 week later, 2 days after surgery. Patient experienced numb-
ness in both legs and back pain. Partial resection of the L4 spinous process with an inhomogeneous mass posterior on the midline. Both axial
T1-weighted imaging before gadolinium (A) and axial T2-weighted imaging (B) show a bright polylobular lesion posterior intraspinal represent-
ing a hemorrhage. C: T1-weighted imaging after gadolinium showing enhancement in the anterior right epidural space representing postoperative
granulomatous changes with a small nonenhancing region: resection of the large herniation shown in Figure 20-15. D: Sagittal T2-weighted imag-
ing showing the hemorrhage as bright (posterior intraspinal) and granulomatous changes as intermediate (anterior intraspinal). Compression of
the dural sac. Reintervention was deemed unnecessary based on clinical findings.

latter is generally accepted to be a possible indication Postoperative Chronic

for further surgery.
Recurrent Pain
A recurrent disc herniation can be differentiated from
epidural scar formation on the basis of existing criteria. Chronic recurrent postoperative pain may have many
Epidural fibrosis shows early enhancement after gado- causes. It is a frequent finding that even has its own name:
linium injection (Figure 20-14). A recent recurrent disc failed back surgery syndrome. The incidence of failed back
herniation initially shows no enhancement because it surgery syndrome is estimated between 10% and 40%.
has no vascularization (Figure 20-15). However, it is sur- Degenerative disease (accelerated or not), spinal steno-
rounded by epidural fibrosis that does show enhance- sis, recurrent disc herniation, meningocele, and arach-
ment. Contrast medium diffuses from this epidural noiditis are frequent causes. However, the main reason
fibrosis into the disc material, causing mild enhance- for failed back surgery syndrome is surgery that was
ment from the outside in, late after contrast injection. performed on a structure that was not responsible for
Therefore, images after gadolinium injection should be the symptoms in the first place. The best way to prevent
acquired as quickly as possible after injection. failed back surgery syndrome is to not perform surgery
620 Section IV Problem Solving: Anatomic Regions

Figure 20-13 Postoperative spondylodiscitis. Sagittal T2-weighted imaging (T2-WI), T1-WI, gadolinium enhanced T1-WI, and subtraction of
T1-WI after and before contrast administration. Typical inflammatory changes seen in spondylodiscitis are edematous changes in the end plates,
bright signal on T2-WI in the disc space, and enhancement in both the disc space and the end plates. Unfortunately, the same changes can be
observed in both infectious postoperative spondylodiscitis and in noninfected (”sterile”) severe inflammatory postoperative changes. Therefore,
the value of imaging mostly lies in the exclusion of infection in case of absence of these changes.

A B
Figure 20-14 Postoperative epidural fibrosis. Axial T1-weighted imaging before (A) and after gadolinium enhancement (B). In this typical
example of (normal) epidural fibrosis, the nonenhanced image shows effacement of the bright fat signal in the left epidural space, marking the
operative changes. This epidural region enhances brightly and completely after gadolinium administration with normal lining of the dural sac
and the nerve roots, which is the expected postoperative image.
 Chapter 20 Spine and Lower Back Pain 621

SECTION IV
A B

C D
Figure 20-15 Postoperative recurrent disc herniation. A: Axial T1-weighted imaging before gadolinium showing effacement of the normal
bright epidural fat on the right. To differentiate between scar and/or a recurrent herniation, intravenous gadolinium is used. B: After gadolinium,
there is subtle peripheral enhancement demonstrating expected postoperative fibrosis. However, centrally in the anterior epidural space is a large
nonenhancing mass corresponding to a large recurrent disc herniation. Axial (C) and sagittal (D) T2-weighted imaging showing the important
mass effect.

that is apt to lead to an unsatisfactory result, hence the narrowing with possible nerve root impingement.
critical importance of thorough preoperative imaging However, altered biomechanics may lead to accelerated
evaluation. Besides the classic discectomy/herniectomy, degeneration of the discovertebral and zygapophyseal
fusion surgery is becoming more popular, also in the joints at the operated segment with consequent spinal
lumbar spine. The main difference in imaging the failed narrowing. This process of altered biomechanics ulti-
spine after fusion surgery is the importance of differen- mately may affect the adjacent levels with accelerated
tiating fusion from nonfusion. This topic is discussed in degeneration at other levels and consequent spinal ste-
the section on Fusion versus Pseudoarthrosis. nosis.

Postoperative Spinal Stenosis Postoperative Meningocele

Removing (part of) an intervertebral disc biomechani- Pseudomeningoceles are CSF-filled collections extend-
cally alters the operated segment. Height loss due to ing from the central spinal canal into the perispinal
either accelerated degeneration or removal of disc soft tissues. It is an uncommon complication, often
material is a typical complication late after discectomy. an incidental finding, that causes no symptoms. They
The main consequence of disc height loss is ­foraminal are not true meningoceles because they have no true
622 Section IV Problem Solving: Anatomic Regions

A B

C D
Figure 20-16 Postoperative meningocele. Sagittal T1-weighted (A) and T2-weighted (B) imaging and axial T1-weighted imaging before
(C) and after gadolinium enhancement (D). A large cystic mass is visible in the laminectomy defect. It has signal intensities identical to cerebro-
spinal fluid (CSF) and shows no enhancement. These postoperative meningoceles develop after inadvertent tears of the meninges with subsequent
collection of CSF. Because they are not lined with meninges, they would be more appropriately called pseudomeningoceles.

arachnoidal lining but instead have walls of reactive Postoperative Arachnoiditis

fibrous tissue. Potential factors inciting chronic sterile spinal arach-
Pseudomeningoceles typically develop after inadver- noiditis are much debated but include the surgical pro-
tent surgical laceration of the dural sac during surgery cedure itself, the presence of intradural blood following
or following incomplete closure of the dural sac in cases surgery, diagnostic lumbar puncture, treated periopera-
of intradural surgery. Usually they protrude through a tive spinal infection, previous use of myelographic con-
surgical bony defect of the posterior spinal elements to trast media (especially older oil-based preparations),
form a cystic lesion with imaging characteristics com- prior intraspinal injection of anesthetic, and antiin-
parable to CSF on both CT and MRI (Figure 20-16). In flammatory or chemotherapeutic agents (e.g., steroids,
the cervical spine, it mostly develops after an anterior methotrexate). Chronically persistent lumbosacral signs
approach, and here it may present a difficult challenge and symptoms in 6% to 16% of postsurgical patients
to treat. Patients with ossification of the posterior longi- have been attributed to sterile arachnoiditis. The three
tudinal ligament are especially prone to dural leaks and MRI patterns described in adhesive arachnoiditis are (1)
resultant pseudomeningocele formation. In some cases, scattered groups of matted or “clumped” nerve roots;
compression of nerve roots and/or spinal cord may (2) an ”empty” thecal sac caused by adhesion of the
occur, causing symptoms. Spinal cord herniation in the nerve roots to its walls; and (3) an intrathecal soft tis-
pseudomeningocele is a rare but serious condition that sue “mass” with a broad dural base, representing a large
requires urgent intervention. group of matted roots, which may obstruct the CSF
 Chapter 20 Spine and Lower Back Pain 623

SECTION IV
A B

C D
Figure 20-17 Postoperative arachnoiditis. Axial T1-weighted imaging before (A) and after gadolinium (B), and axial (C) and sagittal
T2-weighted imaging (D). Axial images demonstrate the small laminectomy defect on the left. Discrete enhancement in the epidural space rep-
resenting normal postoperative fibrosis, no residual disc herniation. C: Axial T2-weighted imaging showing clumped nerve roots in the periphery
of the dural sac that is centrally empty. D: Sagittal image showing the thickened nerve roots regionally in the lower lumbar spine excluding other,
systemic, causes of thickened nerve roots in this case of postoperative arachnoiditis.

pathways (Figure 20-17). These changes may be focal or cervical surgery is performed from anterior in order to
diffuse. Contrast enhancement of the thickened men- avoid manipulation of the spinal cord. Therefore, fusion
ingeal scarring and underlying intrathecal roots may or surgery is relatively more frequent, and the problem of
may not be observed. differentiating epidural fibrosis from recurrent disc her-
niation is nonexistent in imaging of the postoperative
NECK PAIN cervical spine.

Although pathology of the cervical spine resembles that Uncovertebral Degenerative

of the lumbar spine in many ways, there are some signif-
Disease
icant differences. One notable dissimilarity is based on
an anatomic difference: besides discovertebral and zyg- Uncovertebral degenerative disease or short uncarthro-
apophyseal joints, the cervical vertebrae also articulate sis is an important cause of cervical and/or irradiating
in the uncovertebral joints. Uncovertebral degenerative shoulder/arm pain. Besides pain due to the degenerative
disease may cause spinal and/or foraminal narrowing. process itself, the formation of osteophytes with second-
Strangely enough, investigations into the role of the ary narrowing of the neuroforamen is especially signifi-
uncovertebral articulations in cervical pain are almost cant. This foraminal narrowing is well visualized on
nonexistent. Another important difference occurs due to oblique plain film and CT but is sometimes more diffi-
a different surgical approach of cervical pathology. Most cult to quantify on MR due to the susceptibility artifacts
624 Section IV Problem Solving: Anatomic Regions

in this region, which contains fat, water, and bone. This

is most pronounced on gradient-echo sequences that
are often used in the cervical spine. These osteophytic
spurs may extend medially, giving rise to narrowing of
the lateral recess and sometimes the spinal canal. Even
compression of the cervical cord can be seen in severe
cases of uncovertebral degeneration.

Postoperative Cervical Spine

Because of the vulnerability of the spinal cord, most
cervical spine surgery for degenerative disease usually
is performed by an anterior approach. The posterior
approach is mainly reserved for decompression in cases
of spinal stenosis or for surgery of the intradural com-
partment, mainly for dural or medullary lesions.

Fusion versus Pseudarthrosis

The main goal in the anterior approach is to fuse the
painful segment and sometimes to widen the neurofo-
ramen. In order to reach fusion, either bone or an arti-
ficial intervertebral cage is used. Bone can be obtained
from cadavers or can be hosted from the patient, usu- Figure 20-18 Dislodged cervical artificial disc. Anterior displace-
ally from the iliac crest. Bony fusion can be assessed ment/dislodgement of a cervical artificial disc. The most anterior part
using CT or MR. Continuity of bone between both of the artificial disc should never protrude more than 3 mm anterior
vertebrae is the most reliable imaging sign of success- of the intervertebral space. Dislodgement gives subsequent abnormal
motion and loads and usually leads to cervical pain and stiffness.
ful fusion. Although successful cartilage bridging occurs
earlier, bone continuity may sometimes be visible only
12 months or later after surgery. On imaging 6 months
or later after fusion surgery, persistent bone edema (on imbalance, and mechanical wear and/or breakdown.
MRI) and/or a lucency around the cage (on plain film or The most anterior part of the artificial disc can some-
CT) are signs suggestive for nonfusion or pseudarthro- times protrude anterior of the intervertebral space, but
sis. Subsidence or migration of the cage is often accom- anything more than 3 mm has to be considered abnor-
panied by nonfusion. Although fusion is the final goal mal (Figure 20-18). Fusion of the vertebral segment
in this kind of surgery, not all cases of nonfusion are after artificial disc placement can be considered a com-
symptomatic. Most notably, a locked-in cage, although plication but is almost always asymptomatic. Abnor-
technically nonfused, may provide a mechanically sta- mal sagittal alignment, especially cervical kyphosis,
ble situation comparable to fusion. is usually due to abnormal placement and loading of
the artificial disc. It may cause significant cervical pain,
Adjacent Segment Degeneration spinal and foraminal narrowing, and abnormal sec-
A typical complication of cervical spinal fusion is accel- ondary degeneration. Finally, mechanical breakdown
erated degeneration of the adjacent, especially superior, or abnormal wear of the artificial disc presents differ-
segment. A new disc herniation above the successful ently depending on the type used and usually requires
fused segment is a relatively common problem. Its ori- reintervention.
gin is a mechanically altered situation wherein the seg-
ment above the fusion undergoes significantly higher Suggested Readings
forces after, rather than before surgery, possibly leading
to accelerated degeneration. To prevent this complica- Bircher MD, Tasker T, Crawshaw C, Mulholland RC. Discitis following lumbar
surgery. Spine. 1988;13:98-102.
tion, artificial discs are implanted in order to relieve Blackmore CC. Evidence-based imaging evaluation of the cervical spine in
pain caused by degeneration while maintaining spinal trauma. Neuroimaging Clin N Am. 2003 May;13(2):283-291.
Dall BE, Rowe DE, Odette WG, Batts DH. Postoperative discitis. Diagnosis and
mechanics as normal as possible. management. Clin Orthop Relat Res. 1987:138-146.
Milette PC. The proper terminology for reporting lumbar intervertebral disk
Artificial Discs disorders. AJNR Am J Neuroradiol. 1997;18:1859-1866.
Artificial discs have their own typical complications
that usually are easily identifiable on plain films. They
include migration (usually anterior), fusion, sagittal