Atlas of Contrast enhanced Sonography of Focal Liver

Lesions

Visit the link below to download the full version of this book:

https://medipdf.com/product/atlas-of-contrast-enhanced-sonography-of-focal-liver
-lesions/

Click Download Now

To my beloved Giuseppe, Gabriele, Maria Eleonora and Claudia
Foreword

If your pictures aren’t good enough, you aren’t close enough (Robert Capa)

Contrast-enhanced ultrasound (CEUS) represents a significant breakthrough

in sonography and is being increasingly used for evaluation of focal liver
lesions (FLLs). The unique feature of CEUS of non-invasively assessing in
real time liver perfusion throughout the vascular phase has led to a dramatic
improvement in diagnostic accuracy of US in either detection or characteriza-
tion of FLLs, as well as in the guidance and evaluation of response of thera-
peutic procedures. Currently, CEUS is included in many international
guidelines as a part of the suggested diagnostic workup of FLLs, resulting in
a better patient management and cost-effective therapy delivery. This book
offers an image-based, comprehensive quick reference guide that will assist
in the interpretation of CEUS examinations of the liver in daily practice. The
Atlas of Contrast-Enhanced Sonography of Focal Liver Lesions will serve as
an invaluable hands-on tool for practitioners who need to diagnose liver
lesions using CEUS in the major clinical settings: oncology patients, cirrhotic
patients, and patients with incidental focal liver lesions. This book is based on
the daily practice of all the authors who would like to share their endless
enthusiasm and strong commitment to ultrasonography with all the col-
leagues who are interested in the exciting field of contrast-enhanced ultra-
sound of the liver.

Roberto Lagalla
Rector of the University of Palermo
Palermo, Italy

vii
Contents

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 General Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Physical Basis and Specific Contrast
Enhancement Technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.3 Technical Examination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.4 Safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2 Benign Focal Liver Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
2.1 Hepatic Cysts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
2.2 Hydatid Cyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
2.3 Hemangioma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2.4 Focal Nodular Hyperplasia . . . . . . . . . . . . . . . . . . . . . . . . . . 23
2.5 Hepatocellular Adenoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
2.6 Abscesses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
3 Malignant Focal Liver Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . 59
3.1 Primary Malignant Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
3.1.1 Intrahepatic Cholangiocarcinoma . . . . . . . . . . . . . . . 59
3.2 Cirrhotic Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
3.2.1 Regenerative Nodule . . . . . . . . . . . . . . . . . . . . . . . . . 64
3.2.2 Dysplastic Nodule . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
3.2.3 HCC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
3.3 Metastases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
3.3.1 Hypervascular Metastases . . . . . . . . . . . . . . . . . . . . . 76
3.3.2 Hypovascular Metastases . . . . . . . . . . . . . . . . . . . . . 88
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
4 Fatty Liver, Pseudolesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
4.1 Diffuse Fatty Liver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
4.2 Geographic Fatty Change . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
4.3 Focal Fatty Change . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
4.4 Focal Sparing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
4.5 Focal Liver Lesions in Fatty Liver . . . . . . . . . . . . . . . . . . . . . 103
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104

ix
x Contents

5 Other Rare Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105

5.1 Angiomyolipoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
5.2 Solitary Necrotic Nodule . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
5.3 Inflammatory Pseudotumor . . . . . . . . . . . . . . . . . . . . . . . . . . 110
5.4 Hemangiopericytoma (Lypomatous Subtype) . . . . . . . . . . . . 111
5.5 Extramedullary Intrahepatic Hematopoiesis . . . . . . . . . . . . . 112
5.6 Hepatic Splenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
5.7 Epithelioid Hemangioendothelioma . . . . . . . . . . . . . . . . . . . 117
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
6 Assessment of Therapy Response . . . . . . . . . . . . . . . . . . . . . . . . 119
6.1 Locoregional Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
6.1.1 RFTA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
6.1.2 TACE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
6.1.3 Habib Resection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
6.2 Systemic Treatment with Targeted Molecular Therapy . . . . . 136
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
7 Impact of European Guidelines on CEUS . . . . . . . . . . . . . . . . . 139
7.1 Focal Liver Lesions in the Noncirrhotic Liver . . . . . . . . . . . 139
7.2 Focal Liver Lesions in the Cirrhotic Liver . . . . . . . . . . . . . . . 139
7.3 Detection of Metastatic Lesions. . . . . . . . . . . . . . . . . . . . . . . 140
7.4 Monitoring Ablation Treatment . . . . . . . . . . . . . . . . . . . . . . . 140
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
 Introduction
1

1.1 General Overview a reliable, safe, and cost-saving alternative imag-

ing modality able to provide in most cases, in the
Thanks to the most recent technological innova- same US session, a correct characterization of an
tions, the ability of grayscale ultrasound (US) in indeterminate FLL with diagnostic accuracy
the detection of focal liver lesions (FLLs) has comparable to CT or MR performed with state-
significantly improved, even if small or deeply of-the-art scanners thus significantly reducing
located. However, the characterization remains a the number of cases requiring further investiga-
challenge even for experienced sonographers tions [2, 3].
except for hemangiomas with typical US appear- CEUS is a real-time technique thus allowing
ance detected in patients with no history of to continuously study microvessels of FLLs add-
malignancy or chronic liver disease [1]. ing, with respect to CT and MR examinations
Both benign and malignant FLLs can present (sometimes inconclusive), further useful infor-
similar aspect at US, thus making really difficult mation that makes it a helpful problem-solving
a correct differential diagnosis especially when imaging modality.
liver echotexture is altered such as in chronic The European Federation of Societies for
hepatitis or diffuse fatty infiltration. In particular, Ultrasound in Medicine and Biology (EFSUMB)
this latter, increasing the ultrasound beam attenu- also recommends CEUS especially in peculiar
ation, also hinders lesion’s identification, and the clinical settings as, for example, in the diagnosis
majority of liver masses appear hypoechoic of incidentally discovered FLLs indeterminate at
regardless of tumor’s nature. US or in the evaluation of locoregional
Moreover, color and power Doppler evalua- treatment.
tion slightly improves diagnostic performance of At this regard, a newly developed CEUS tech-
US examination since they visualize large vessels nique, three-dimensional CEUS (3D-CEUS) per-
and are limited by motion artifacts, making the formed by means of a 3D probe, has been
analysis often unsatisfactory and thus inconclu- reported to improve the study of tumor vascular-
sive for the differential diagnosis of FLLs. ity in the three orthogonal planes, allowing the
In the last decades, the development of both visualization of the region of interest from differ-
second-generation ultrasound contrast media and ent points of view.
specific software for contrast agent detection has In some cases regarding locoregional treat-
significantly improved diagnostic accuracy of US ment CEUS evaluation, an example of a particu-
in terms of sensitivity and specificity. Nowadays, lar 3D reconstruction software called “i-slice”
contrast-enhanced ultrasound (CEUS) represents will be showed in this atlas. I-slice provides the

© Springer International Publishing Switzerland 2015 1

T.V. Bartolotta et al., Atlas of Contrast-enhanced Sonography of Focal Liver Lesions,
DOI 10.1007/978-3-319-17539-3_1
2 1 Introduction

capability of displaying the data set in multiple, Due to the flexibility of the microbubbles’
contiguous, parallel 2D slices, similar to CT and phospholipid shell, the reflectivity of SonoVue is
MR, changing the interval (distance between the very high with high echo enhancement. On the
individual slices) and the depth setting (the posi- other hand, due to the poor solubility and diffu-
tion of the slices in the volume) in order to better sivity, this contrast agent is also strongly resistant
display the region of interest [4, 5]. to pressure. This allows minimally disruptive
So the aim of this atlas is to describe by means contrast-specific imaging at mechanical index
of a wide collection of clinical cases the most (MI) set in clinical practice and enables effective
common imaging patterns of benign and malig- investigations over several minutes with the visu-
nant FLLs evaluated by means of CEUS in order alization of the dynamic enhancement pattern in
to make the specialist who would like to perform real time. Low-MI techniques furthermore lead
it confident in the interpretation of imaging find- to effective tissue signal suppression as the non-
ings and able to provide pivotal information for a linear response from the tissue is minimal when
definitive characterization during the same ses- low acoustic pressures are used.
sion of a baseline US examination avoiding fur- In summary, low-MI imaging with second-
ther imaging workup. generation contrast agent (i.e., SonoVue) allows
real-time examination and the evaluation of con-
trast medium distribution from the beginning of
1.2 Physical Basis and Specific intravenous injection up to 4–5 min.
Contrast Enhancement
Technique
1.3 Technical Examination
The ultrasound contrast agents (UCAs) currently
used in diagnostic US are characterized by a In our department, CEUS examination involves
microbubble structure consisting of gas bubbles the use of US scanners equipped with convex
stabilized by a shell. UCAs act as blood pool probe and Pulse Inversion Harmonic Imaging soft-
agents. They strongly increase the US backscat- ware, extremely sensitive to microbubble-based
ter and therefore are useful in the enhancement of US contrast agents. The first part of the study
blood echogenicity for the assessment of blood includes a preliminary assessment of hepatic
flow in the micro- and macrovessels. SonoVue© parenchyma in grayscale—including color power
contains low-solubility gas (sulfur hexafluoride) Doppler and pulsed Doppler analysis—in order to
microbubbles surrounded by a flexible phospho- localize the lesion and select an appropriate scan-
lipid shell improving microbubble stability. The ning plane. Once set, the US scan parameters—
microbubbles have a mean size of 2.5 µm with such as focal zone, time gain compensation,
99 % of them smaller than 11 µm allowing a free MI—remain unchanged throughout the study. The
passage in the capillaries but keeping the contrast US contrast agent (USCA) is sulfur hexafluoride
medium within the lumen. filled microbubble based (SonoVue®, Bracco,
The assessment of microbubbles usually Milan, Italy), intravenously injected as a 2.4 mL
requires contrast-specific imaging modes. bolus followed by 10 mL of sterile saline flush by
Contrast-specific US softwares are generally using a 20- or 22-gauge peripheral cannula. In
based on the cancellation and/or separation of order to minimize microbubble disruption, a low
linear US signals from tissue and utilization of frame rate (5 Hz) and a low MI, usually 0.06, are
the nonlinear response from microbubbles. used for real-time imaging.
Nonlinear response from second-generation Digital cineloops are registered, respectively,
contrast agents is based on nonlinear response during the arterial, (i.e., 10–40 s from beginning
from microbubble oscillations at low acoustic of contrast agent bolus injection) and extended
pressure, reducing disruption of the portal venous phase (i.e., until 200–300 s from
microbubbles. beginning of injection).
References 3

Considering that currently used USCAs are microvascular disruption can occur when micro-
blood pool agents, without any interstitial or bubbles are insonated [8]. Thus, in general, low
equilibrium phase, some authors describe a MI should be preferred for CEUS of the liver.
unique extended portal venous phase starting just Some general recommendations include the fol-
after the arterial phase and progressively fading lowing: (a) as in all diagnostic ultrasound proce-
up to 3 min [6]. dures, the operator should be mindful of the
All images and cineloops are digitally stored desirability of keeping the displayed MI low and
both as raw data in a PC-based workstation con- of avoiding unduly long exposure times; (b) cau-
nected to the US units via a standard Ethernet tion should be exercised when using UCA in
link and sent to a Picture Archiving and patients with severe coronary artery disease, clin-
Communication System (PACS). ically unstable ischemic cardiac disease, right-to-
When multiple lesions are present in the same left shunts, severe pulmonary hypertension,
patient, multiple doses can be injected in order to uncontrolled systemic hypertension, and adult
study each one with an interval time of at least respiratory distress syndrome; (c) as with all con-
10 min making sure there are no more contrast trast agents, resuscitation facilities must be avail-
medium microbubbles within the vessels. able; (d) the use of UCA should be avoided 24 h
Otherwise, before any further injection, the entire prior to extracorporeal shock wave therapy [9].
liver parenchyma can be scanned at high MI (1.3) Caution with respect to the use of UCAs in
in order to destroy any remaining ones. these cardiac instances derives from an anecdotal
Baseline echogenicity and dynamic enhance- temporal but unproven causal association
ment pattern of each lesion are evaluated in the between contrast injection and death in severely
arterial and extended portal-venous phase in compromised cardiac patients. However, in very
comparison with adjacent liver parenchyma. large patient cohorts, the use of UCAs for acute
cardiac patients has been shown to be associated
with a decreased, not increased, risk of death
1.4 Safety thanks to the efficacy of the modality [10, 11].
UCAs are not licensed in pregnancy or in
In general, UCAs are extremely safe with a low pediatric patients. Nevertheless, some authors
incidence of side effects. They are not nephro- have recently reported their experience about off-
toxic or cardiotoxic, and the incidence of hyper- label use of UCA in pediatric patients [12, 13].
sensitivity or allergic events appears much lower
than current CT or MR contrast agents. It is not
necessary to perform laboratory tests of renal
function before administering them. References
Life-threatening anaphylactoid reactions in
abdominal applications have been reported with a 1. Bartolotta TV, Taibbi A, Midiri M, Matranga D,
rate of 0.001 %, with no deaths in a series of Solbiati L, Lagalla R (2011) Indeterminate focal liver
lesions incidentally discovered at gray-scale US: role
> 23 ,000 patients [7]. of contrast-enhanced sonography. Invest Radiol
Nonetheless, investigators should be trained in 46(2):106–115
resuscitation and have the appropriate facilities 2. Malhi H, Grant EG, Duddalwar V (2014) Contrast-
available. enhanced ultrasound of the liver and kidney. Radiol
Clin North Am 52(6):1177–1190
Although there is a theoretical possibility that 3. Cantisani V, Grazhdani H, Fioravanti C, Rosignuolo
the interaction of diagnostic ultrasound and UCA M, Calliada F, Messineo D, Bernieri MG, Redler A,
could produce bioeffects, there is no clinical evi- Catalano C, D’Ambrosio F (2014) Liver metastases:
dence for adverse effects on the human liver. contrast-enhanced ultrasound compared with com-
puted tomography and magnetic resonance. World J
Cellular effects that have been observed in vitro Gastroenterol 20(29):9998–10007
include sonoporation, hemolysis, and cell death. 4. Bartolotta TV, Taibbi A, Midiri M, De Maria M
Data from small animal models suggest that (2008) Hepatocellular cancer response to radiofre-
4 1 Introduction

quency tumor ablation: contrast-enhanced ultrasound. DA, Correas JM, Ding H, Forsberg F, Fowlkes JB,
Abdom Imaging 33(5):501–511 Gibson RN, Goldberg BB, Lassau N, Leen ELS,
5. Bartolotta TV, Taibbi A, Matranga D, Midiri M, Mattrey RF, Moriyasu F, Solbiati L, Weskott H-P, Xu
Lagalla R (2015) 3D versus 2D contrast-enhanced H-X (2013) Guidelines and good clinical practice rec-
sonography in the evaluation of therapeutic response ommendations for Contrast Enhanced Ultrasound
of hepatocellular carcinoma after locoregional thera- (CEUS) in the liver – update 2012. A WFUMB-
pies: preliminary findings. Radiol Med [Epub ahead EFSUMB initiative in cooperation with representa-
of print] tives of AFSUMB, AIUM, ASUM, FLAUS and
6. Burns PN, Wilson SR (2007) Focal liver masses: ICUS. Ultrasound Med Biol 39(2):187–210
enhancement patterns on contrast-enhanced images— 10. Main ML, Goldman JH, Grayburn PA (2009)
concordance of US scans with CT scans and MR Ultrasound contrast agents: balancing safety versus
images. Radiology 242:162–174 efficacy. Expert Opin Drug Saf 8:49–56
7. Piscaglia F, Bolondi L, Italian Society for Ultrasound 11. Main ML, Ryan AC, Davis TE et al (2008) Acute
in Medicine and Biology (SIUMB) Study Group on mortality in hospitalized patients undergoing echocar-
Ultrasound Contrast Agents (2006) The safety of diography with and without an ultrasound contrast
Sonovue in abdominal applications: retrospective agent (multicenter registry results in 4,300,966 con-
analysis of 23188 investigations. Ultrasound Med secutive patients). Am J Cardiol 102:1742–1746
Biol 32(9):1369–1375 12. Coleman JL, Navid F, Furman WL, McCarville MB
8. Skyba DM, Price RJ, Linka AZ, Skalak TC, Kaul S (2014) Safety of ultrasound contrast agents in the
(1998) Direct in vivo visualization of intravascular pediatric oncologic population: a single-institution
destruction of microbubbles by ultrasound and its experience. AJR Am J Roentgenol 202(5):966–970
local effects on tissue. Circulation 98(4):290–293 13. Schreiber-Dietrich DG, Cui XW, Piscaglia F, Gilja
9. Claudon M, Dietrich CF, Choi BI, Cosgrove DO, OH, Dietrich CF (2014) Contrast enhanced ultra-
Kudo M, Nolsøe CP, Piscaglia F, Wilson SR, Barr sound in pediatric patients: a real challenge. Z
RG, Chammas MC, Chaubal NG, Chen M-H, Clevert Gastroenterol 52(10):1178–1184
 Benign Focal Liver Lesions
2

2.1 Hepatic Cysts should suggest an abscess, parasitic infection, or

cystic neoplasm. In particular, at CEUS, cystic
A simple hepatic cyst is a single, unilocular tumors of biliary origin and cystic metastasis usu-
lesion containing homogeneous serous fluid sur- ally present a thick capsule, thick internal septa, or
rounded by a single layer of cuboidal epithelium, mural nodules which show contrast enhancement
identical to that of bile ducts, and a thin underly- suggesting the presence of viable tissue [2].
ing layer of fibrous stroma [1]. Furthermore, hemorrhagic or complicated
Usually, a correct diagnosis is already allowed cysts may show hypoechoic inhomogeneous
by means of grayscale US thanks to a homoge- appearance instead of typical anechoic aspect on
neous anechoic appearance, a thin or imperceptible conventional US scan. In these cases, CEUS can
wall with posterior acoustic enhancement. Some depict the absence of vascularization throughout
internal thin septa may be present, but thick septa the vascular phase, suggesting cystic nature.

© Springer International Publishing Switzerland 2015 5

T.V. Bartolotta et al., Atlas of Contrast-enhanced Sonography of Focal Liver Lesions,
DOI 10.1007/978-3-319-17539-3_2
6 2 Benign Focal Liver Lesions

Fig. 2.1 Complicated cyst in a 48-year-old man. (a) lar signal at power-Doppler evaluation (arrow). (b–d) At
Oblique ascending right subcostal baseline image shows a CEUS, the lesion shows lack of contrast enhancement
markedly hypoechoic lesion sized 3.5 cm in the subcapsu- throughout the vascular phases (arrows)
lar region of the VII hepatic segment not showing vascu-
2.1 Hepatic Cysts 7

Fig. 2.1 (continued)

8 2 Benign Focal Liver Lesions

2.2 Hydatid Cyst sion, and Budd-Chiari syndrome. At baseline US,

hydatid cysts may present a solid aspect because of
Hydatid disease is a parasitic infestation by a its inhomogeneous complex appearance. Parasitic
tapeworm of the genus Echinococcus. cyst usually presents as a single, unilocular cyst or
Cystic hydatid disease usually affects the liver multiseptated cysts, showing “wheel-like,”
(50–70 %) and less frequently the lung, the spleen, “rosette-like,” or “honeycomb-like” appearances.
the kidney, the bones, and the brain. Liver hyda- “Snowstorm” sign may appear as multiple internal
tidosis can cause dissemination or anaphylaxis echogenic foci within the cyst cavity (hydatid
after a cyst ruptures into the peritoneum or biliary sand). A correct diagnosis is of clinical relevance
tract. Infection of the cyst can facilitate the devel- since biopsy of these lesions is not recommended
opment of liver abscesses and mechanic local com- in order to avoid severe adverse events. Usually,
plications, such as mass effect on bile ducts and CEUS shows lack of enhancement of septa separat-
vessels that can induce cholestasis, portal hyperten- ing daughter cysts [3, 4].

a b

Fig. 2.2 Hydatid cyst with daughter cysts in a 62-year- cystic areas is detected in the right hepatic lobe (arrows).
old man. (a) At baseline US, a large heterogeneous (b) CEUS depicts the lesion as a constantly avascular
hypoechoic mass sized 13.1 cm with multiple internal mass (arrows)