Journal of Biomedical Optics 11共4兲, 041102 共July/August 2006兲

Review of tissue simulating phantoms for optical

spectroscopy, imaging and dosimetry
Brian W. Pogue Abstract. Optical spectroscopy, imaging, and therapy tissue phan-
Dartmouth College toms must have the scattering and absorption properties that are char-
Thayer School of Engineering acteristic of human tissues, and over the past few decades, many use-
Hanover, New Hampshire 03755
ful models have been created. In this work, an overview of their
composition and properties is outlined, by separating matrix, scatter-
Michael S. Patterson ing, and absorbing materials, and discussing the benefits and weak-
Juravinski Cancer Center nesses in each category. Matrix materials typically are water, gelatin,
Department of Medical Physics agar, polyester or epoxy and polyurethane resin, room-temperature
Hamilton, Ontario, Canada vulcanizing 共RTV兲 silicone, or polyvinyl alcohol gels. The water and
and
McMaster University
hydrogel materials provide a soft medium that is biologically and bio-
Hamilton, Ontario, Canada chemically compatible with addition of organic molecules, and are
optimal for scientific laboratory studies. Polyester, polyurethane, and
silicone phantoms are essentially permanent matrix compositions that
are suitable for routine calibration and testing of established systems.
The most common three choices for scatters have been: 共1.兲 lipid
based emulsions, 共2.兲 titanium or aluminum oxide powders, and 共3.兲
polymer microspheres. The choice of absorbers varies widely from
hemoglobin and cells for biological simulation, to molecular dyes and
ink as less biological but more stable absorbers. This review is an
attempt to indicate which sets of phantoms are optimal for specific
applications, and provide links to studies that characterize main phan-
tom material properties and recipes. © 2006 Society of Photo-Optical Instrumen-
tation Engineers. 关DOI: 10.1117/1.2335429兴

Keywords: tissue simulating phantoms; optical spectroscopy; imaging; dosimetry.

Paper 05287SSR received Sep. 30, 2005; revised manuscript received Jan. 10, 2006;
accepted for publication Jan. 11, 2006; published online Sep. 1, 2006.

1 Introduction for minimum performance criteria for new systems and for
1.1 Medical Tissue-Simulating Phantoms routine monitoring of existing systems. The benefit of this
procedure is that system performance can then be made more
The development of all diagnostic imaging systems and most uniform between institutions and over time.
physical therapeutic interventions has required the use of Access to these phantoms is made possible through com-
tissue-simulating objects to mimic the properties of human or mercial distributors who can manufacture them economically.
animal tissues. These so-called “phantoms” are used for a Unfortunately, in the development phase of imaging systems,
number of purposes,1–3 including: the status of tissue phantoms can be inconsistent and change
1. initially testing system designs over time, making comparison of research systems more dif-
2. optimizing signal to noise in existing systems ficult. In addition, considerable wasted effort occurs in rede-
3. performing routine quality control veloping tissue phantoms that have already been well de-
4. comparing performance between systems signed by previous groups. In the case of optical or near-
When systems are established and in routine clinical use with infrared imaging and spectroscopy, the field has developed
regulatory approval, there are generally requirements or rec- considerably over the past several decades, yet routine wide-
ommendations for quality control phantoms that need to be spread clinical use has not been established for many systems.
imaged for validation of system performance and use. Regu- In addition, the spectral range and geometrical range of optics
latory bodies such as the American College of Radiology applications are so diverse that development of systems and
共ACR兲, and medical physics associations such as the Ameri- tissue phantoms has not been a straightforward linear progres-
can Association of Physicists in Medicine 共AAPM兲 and/or sion. In this study, an overview of the various types of tissue
simulating phantoms and their applications is outlined. An
Canadian Organization of Medical Physicists 共COMP兲 make
attempt is made to discuss the strengths and weaknesses of
recommendations on requirements for phantoms to be used
each phantom type, and issues such as system purpose, geom-
etry, and tissue type are included. The tradeoffs between
Address all correspondence to Brian Pogue, Thayer School of Engineering, Dart- structure and biological or chemical function are also in-
mouth College, 8000 Cummings Hall, Dartmouth College Hanover, NH 03755
United States of America; Tel: 603 646-3861; Fax: 603 646-3856; E-mail:
pogu@[Link] 1083-3668/2006/11共4兲/041102/16/$22.00 © 2006 SPIE

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 Pogue and Patterson: Review of tissue simulating phantoms¼

cluded, in an effort to provide the most comprehensive listing introduced is there a discernable separation of the effects of
possible at this stage of development. ␮a and ␮s⬘. If the goal is to mimic the tissue transmission,
The history of tissue simulating phantoms for optical or then matching ␮eff can often be sufficient, but in most tissue
near-infrared spectroscopy and imaging of tissue began in the spectroscopy applications where the goal is to separate ␮a共␭兲
early 1980s with the surge of clinical interest in near-infrared and ␮s⬘共␭兲 to allow spectral fitting, the tissue must have rep-
transillumination for breast cancer imaging, also termed resentative values for both these parameters. An excellent
diaphanography.4–7 Later interest also arose from applications compendium of tissue optical properties was compiled in the
in photodynamic therapy treatment planning and pulsed laser late 1980’s by Cheong, Prahl, and Welch,41 and updated in
treatment planning,8–14 where knowledge of the optical flu- 1995.42 Since that time, many more spectra have been pro-
ence distribution in tissue was critical to achieving treatment duced for dozens of different tissue types, including
efficacy. In the early 1990s, the introduction of spatially re- breast,43–47 brain,48 skin,49,50 esophagus, and cervix.51–54
solved, time-resolved, and frequency-domain light signals
spurred a larger number of researchers to investigate spectros- 1.3 Molecular/Flow/Structural Complexities of
copy and imaging of tissue, leading to the generation of many Optical Phantoms
different types of tissue phantoms.15–23 In recent years, the
applications of light in medicine have increased dramatically, Most of the early studies in tissue phantoms were focused on
with cosmetic laser surgery being a major commercial driving creating regular-shaped objects that mimicked tissue reduced
force, and fluorescence and reflectance diagnostics emerging scattering ␮s⬘ and absorption ␮a at specific wavelengths. In
as serious contenders for commercial success. Research into the past decade, focus has shifted to providing phantoms that
near-infrared tomography,24–29 photodynamic therapy reproduce tissue properties over broader wavelength ranges,
dosimetry,8,12,30 luminescence imaging,31–33 fluorescence mo- matching the full spectrum of tissue ␮a共␭兲 and ␮s⬘共␭兲 values.
lecular imaging,34–36 and optical coherence tomography37 There is also significant interest in developing biochemical
among other applications, keeps the area of tissue phantoms and biologically compatible tissue phantoms, which can uti-
progressing and important. Experimental progress toward mo- lize biologically important molecules such as hemoglobin,
lecular imaging applications requires tissue phantoms that melanin, or endogenous fluorophores such as nicotinamide
have some of the specific molecular features of human tissue. adenine dinucleotide 共NADH兲 and flavin adenine dinucleotide
At the same time, companies are developing tissue imaging 共FAD兲55 or exogenous fluorphores such as porphyrins or cya-
and spectroscopy devices that will require well-calibrated tis- nine dyes.56 Extending the biochemical capacity to measuring
sue phantoms for routine system comparison, evaluation, and transient biochemical species such as radicals or singlet oxy-
quality control. For all of these reasons, the improvement and gen has also been demonstrated, and provides actinometry
standardization of tissue optical phantoms is essential and capabilities for therapy planning and optimization.57,58
likely inevitable, even though this work has low priority in Generation of hybrid phantoms with specific characteris-
most research labs. tics for multimodality imaging, such as elastic properties,59
biochemical properties, water/lipid concentrations,60 electrical
properties,61 magnetic resonance properties, and thermal prop-
1.2 Tissue Optical Properties erties, together with optical properties, is becoming increas-
The key to matching tissue properties in phantoms is a com- ingly useful.62
prehensive understanding of the key physical and biochemical Along the lines of dynamically changeable phantoms,
characteristics of tissue that influence its interaction with there is also a need in some developments to study motion or
light.13 For small scale 共⬍1 mm兲 applications, it is likely im- mass displacement with optical signals. Several methods have
portant to match the absorption coefficient ␮a共␭兲, the scatter- been developed to image motion in tissue, which ultimately
ing coefficient ␮s⬘共␭兲, and the anisotropy coefficient g共␭兲, provides a good measure of mass flow, either by Doppler shift
which is defined as the average cosine of the scattering angle. measurements63,64 or correlation analysis of speckle.65–68
Over larger distances 共more than 3 to 5 scattering lengths, a In recent years, with advances in tissue engineering, a new
scattering length being defined as the reciprocal of the scat- emphasis has been placed on engineered tissue structures as
tering coefficient 1 / ␮s兲 matching the reduced scattering coef- tissue-simulating phantoms for studies that investigate bio-
ficient ␮s⬘ 关also called the transport scattering coefficient, de- logical chemistry or complex biochemical signatures.69 This
fined as ␮s⬘ = 共1-g兲␮s兴 is all that is required.21 This “reduced” approach and the use of ex-vivo tissue70,71 have become estab-
approximation follows observations in neutral particle scatter- lished areas of investigation, although their use is distinctly
ing that over multiple scattering event lengths, an anisotropic different from the standard concept of a tissue phantom. The
scattering process appears identical to an isotropic scattering ability to better test systems in realistic situations with thin
process with a reduced value for the effective scattering tissue layers, anisotropic properties, and extracellular scaf-
coefficient.12,38–40 In many cases of thick tissue transmission, folding is essential in some applications. Each of these sub-
it is possible to get away with mimicking the effective attenu- jects is addressed in detail in this work.
ation coefficient of a tissue, defined in the wavelength regime
where diffusion theory is accurate as ␮eff = 共3␮a␮s⬘兲−1/2. This 1.4 Optical Tissue Phantom Composition Choices
is possible because steady-state attenuation in homogeneous In choosing the most useful phantom materials and design, the
media is affected in the same way by the same relative change region of the spectrum to be used is important, as are the
in absorption or scattering. Over long distances, diffusive pro- geometrical design parameters of thickness, heterogeneities,
cesses appear to be attenuated exponentially with this single container, and possible machining constraints. The biological
coefficient, and only when boundaries or temporal signals are compatibility in terms of biochemical action or inclusion of

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Table 1 Scattering constituents of optical phantoms.

Particle
Scatterer Biologically Organic Particle Index of distribution
material Permanent compatible chemical size 关nm兴 refraction function Recommended Use References
7,30,60,80,81,148,149
Lipids N Y Y 10 to 500 1.45 Exponentially Intralipid, milk, mixture
nm weighted to Theory/experimental
smaller sizes, tests and multiple phantom
impossible to contrast studies
get a single
size
distribution

Polymer Y Y Y 50 nm to 1.59 Single size Most accurate theoretical 1. Bangs Laboratories

microspheres 100 ␮m function as prediction of properties 共Fishers, IN兲
ordered, with Used with all aqueous, 2. Polysciences Inc.,
possible 1 to 2% resin, and RTV phantoms Warrington, PA, and
variance. Eppelheim, Germany兲
3. Duke Scientific Inc.
共Palo Alto, CA兲.
55,109,150,151

TiO2 Y Y Y 20 to 70 2.4 to Exponentially Used with gelatin, RTV, Sigma-Aldrich Inc.

Al2O3 nm 2.9 weighted or and resin phantoms commonly cited
powders single size can Many possible
be ordered manufacturers and
distributors
Many different forms

Quartz glass Y Y Y 250 nm N/A Single size Used with resin Darmstadt Inc.,
microspheres function, with phantoms Germany152
10% variance

biologically relevant chromorphores and fluorophores is criti- 1. validation of physical models and simulations
cal as well. Since one of the important features of optical and 2. instrument performance testing and optimization
near-infrared 共NIR兲 spectroscopy is the spectral sensitivity to 3. instrument calibration and testing of stability and
molecular features of tissue, it has become increasingly im- reproducibility
portant to develop reliable phantoms that accurately mimic 4. interlaboratory comparison and standardization.
the chemistry of tissue. This requires a shift away from solid The properties of the ideal phantom depend on its intended
nonorganic polymers and silicone phantoms toward biologi- use. For example, validation phantoms need to be precisely
cally compatible structures such as agar, gelatin, or collagen characterized, but stability and reproducibility might not be as
matrixes that allow easy inclusion of cellular constituents important as in phantoms intended for interlaboratory com-
such as blood or fat and fluorescent molecules such as parisons. Thus, as the different phantoms are discussed, these
NADH, FAD, porphyrins,72,73 and other exogenous organic
four uses are kept in mind.
luminescent molecules.74–76.
An “ideal” phantom that could be used for any application
In this survey, the strengths of each approach are put
would have the properties listed as follows. As stated before,
alongside the ease of use, and in Tables 1–8 a summary of
these is included, along with recommendations for use for in real applications only some of these properties are impor-
each type of phantom. Because of the wide variety of phan- tant and the others can be neglected or given a lower priority.
toms and their constituents, it is not possible to have a single 1. Absorption and scattering properties can be varied as in
comprehensive table of constituents without having signifi- different tissues.
cant redundancy and overwhelmingly long tables. In an effort 2. Wavelength dependence of these properties is similar to
to streamline the presentations, the important parameters for tissue.
tissue optical phantoms are separated into scattering particles 3. Molecules of specific interest can be incorporated 共e.g.,
and matrix material. In the sections that follow, more detailed NADH, FAH, collagen, tetrapyrroles, fluorophores, and
discussion of each is provided to include all the pertinent actinometers兲.
details, and to reference the key studies that provide more 4. Properties are stable over time and environmental con-
complete directions of how to make and use these phantoms. ditions 共e.g., temperature, humidity, and photobleaching兲.
5. Index of refraction close to that of tissue 共e.g., index of
1.5 Purposes of Phantoms and the Criteria for tissue ⬇1.4兲.
Determining Their Value 6. Ability to incorporate regions with different optical
In general, the purposes of tissue optical phantoms can be properties 共e.g., inclusions mimicking tumors or layers mim-
roughly divided into the following categories: icking skin兲.

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 Pogue and Patterson: Review of tissue simulating phantoms¼

7. Mechanical and surface properties are similar to tissue Table 2 Summary of lipid emulsion-based phantoms.
共e.g., Young’s modulus near 4 to 20 kPa兲.77
8. Ability to incorporate Brownian motion or flow in the Scatterer Function Limitations Stability References
phantom. 6,149,153
9. Ability to include thermal properties similar to tissue. Milk Readily available Not highly Hours
reproducible
10. Ease of manufacturing.
between
11. Inexpensive to produce. samples
12. Easily transported between different sites.
7,60,106
Again, as the different compositions are analyzed, these fea- Oil/fat/lipid Used to custom- Must be Hours
tures are raised and discussed to compare each phantom ma- make scattering emulsified
terial with alternatives. and lipid/water and blended
phantoms reproducibly
80,81,148
2 Scattering Particles in Optical Phantoms Intralipid/ Reproducible Stability better Days
Nultralipid source of lipid than 10%
In most tissue phantoms, the choice of a scattering agent is solution
separate from the choice of matrix composition, as the volume
fraction of the scattering material is typically less than 5% of
the total, and often less than 1%. There have been three main
choices: lipid microparticles, polymer microparticles, and tency in the optical properties between batches. Clearly this is
white metal oxide powders and a brief list is shown in Table an emulsion suspension, and thorough mixing is required for
1. The benefit of lipid microparticles is that they are biologi- homogeneity. The homogeneity lasts for a period of hours,
cally similar to what is thought to cause scattering in tissue, while reuse of the solution has been reported over many days.
namely the bilipid membrane of cells and organelles. The next When used for ultraviolet studies, the lipid content in this
most common choice has been the polymer microsphere, with medium is likely to fluoresce which may interfere with trans-
polystyrene being the most popular. This is an excellent mission or remission studies, and so care must be taken to use
choice from a scientific perspective, because it is produced in nonorganic scattering materials such as are described in the
regular sizes with good quality control over the size and index next two sections.
of refraction. Thus, the repeatibilty and theoretical prediction
of the spectra are excellent. The third choice is common tita- 2.2 Scattering Coefficient Spectrum of Intralipid
nium dioxide or aluminum oxide powder. These are often the An excellent survey of the properties of Intralipid can be
main pigment in white paint and white plastics, due to their found at the website [Link]
high scattering coefficients, and they can be obtained in well- The most cited study by van Staveren et al.81 used measure-
controlled spherical formulations, although the use of these is ments of optical transmission as well as electron microscopy
less well established. Finally, in recent years scattering gold and Mie theory calculations to estimate the scattering spec-
nanoparticles have been developed, and their use in tissue trum. They also proposed a simple power law for the wave-
diagnostics and therapy has considerable promise due to their length dependence of the reduced scattering coefficient, which
high scattering cross section and potential has been utilized by many researchers. For a standard 10%
biocompatibility.78,79 While their use in phantoms is not well stock solution, the formulas for scattering and anisotropy co-
established, their significant Mie scatter cross section makes efficients are:
them a good potential scatterer. Each of these is discussed in
more detail later, and summarized in Table 1. ␮s共␭兲 = 16␭−2.4 ,

2.1 Commercially Available Lipid-Based Scatterers units of mm−1, when ␭ is in microns, and
The most widely used phantoms for optical imaging and spec- g共␭兲 = 1.1 − 0.58␭,
troscopy have been the liquid type, made from milk149 or
emulsified oil suspensions initially, and later being largely re- resulting in the equation for reduced scattering coefficient of:
placed with the well calibrated, commercially available lipid
emulsion with the trade name Intralipid.148,152 These are listed ␮s⬘共␭兲 = 9.3␭−1.4 − 1.6␭−2.4 共units of mm−1兲 .
in Table 2. For a more complete spectrum across the visible range, inclu-
Commerical supplies of calibrated lipid solutions are pos- sion of Rayleigh scattering is likely needed, requiring a third
sible due to their production for intravenous feeding.82 There term having the standard ␭−4 power function, but requiring
is a number of commercial manufacturers, and the trade name fitting for the coefficient. Many analyses retain only the first
of the product varies between manufacturers. Intralipid™
term of this latter formula, and fit ␮s⬘共␭兲 to the functional
共Kabi-Pharmacia, Erlangen Germany; Pharmacia and Upjohn,
form ␮s⬘共␭兲 = a␭−b, with a and b as free parameters. When
Clayton, New Jersey; and Kabi-Vitrum Incorporated, Stock-
fitting is restricted to the near infrared, this can be a reason-
holm, Sweden兲 is the most commonly cited word, with other
able assumption over a limited wavelength range.
versions called Nutralipid™ 共Pharmacia, Quebec, Canada兲
and Liposyn II™ 共Abbott Labs Incorporated, Montreal兲. This
solution is readily available in all hospital pharmacy depart- 2.3 Polymer Microspheres
ments, and the uniformity between batches is thought to be From a scientific viewpoint, polystyrene microspheres pro-
excellent, although there is some contention about the consis- vide the best standard phantom, as they are well controlled in

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Table 3 Phantom matrix options to hold the scatterers, absorbers, and fluorophores.

Phantom Solid/ Organic

matrix liquid/ Biologically chemical Inclusions Adjustable Adjustable Index of Recommended
material Permanent flexible compatible compatible possible? absorption scattering refraction use References
7
Aqueous N L Y Y Y Y Y 1.34 Initial use and
suspension multiple phantom
contrast studies
55
Gelatin/agar N F Y Y Y Y Y 1.35 Detailed
matrix heterogeneity
phantom studies
bioabsorbers and
fluorophores
154
Polyacrylamide N F Y Y Y Y Y 1.35 Thermal therapy
gel studies
109,111,155,152
Polyester or Y S N N Y Y Y 1.54 Calibration and
epoxy resin routine validation
Intersystem
comparisons
114
Polyurethane Y S N N Y Y Y 1.50 Calibration and
resin routine validation
Intersystem
comparisons
Inclusion of dyes
117
RTV silicone Y F N N Y Y Y 1.4 Complex
geometries with
permanent flexible
phantoms

size and index of refraction.15 Their use has been included in

fundamental Mie scattering theory modeling studies, and their
scattering coefficient properties validated in dilute and bulk
g = 具cos共␪兲典 = 冕
4␲
P共␪兲cos共␪兲d⍀,

samples. The ability to have a phantom that matches the pre-

dicted scattering coefficient of Mie theory provides a level of
validation that does not exist in any other system. Thus, this
1 dCscat
phantom is perhaps the best for validation of absolute optical where P共␪兲 = .
property calculations. Microspheres of different composition Cscat d⍀
can be obtained from commercial suppliers: 1. Bangs Labo-
ratories, Fishers, Indiana兲; Polysciences Incorporated, War- These formulas have been used to show that with polystyrene
rington, Pennsylvania and Eppelheim, Germany; 3. Duke Sci- in water or glycerin, the measured scattering matches the pre-
entific Incorporated, Palo Alto, California. dicted value quite accurately. Computational solvers for these
Prediction of the scattering coefficient based on the Mie Mie expressions are available at several locations, with com-
theory has been repeatedly shown to be a valid way to predict prehensive resources at the following websites [Link]
the bulk scattering properties of polystyrene microspheres in [Link]/ or [Link]
solution. Following the derivation provided by Bohren and wriedt/New/new.php3. These all refer to the original programs
Huffman,83 the following equation for the reduced scattering developed by Bohren and Huffman in 1983,83 but several of
coefficient can be obtained: the newer versions have more efficient solvers for the Bessel
function expansion, and provide solutions in newer program-
p ming languages, such as MATLAB and Mathematica.
␮s⬘共␭兲 = N 兺 f 共ai兲Cscat共m,ai,␭兲关1 − g共m,ai,␭兲兴 , Addition of absorbers of all kinds is possible with these
i=1 phantoms; however, molecular absorbers are probably prefer-
able, as the phantoms can then last for years and be reused as
where Cscat is calculated by a series expansion of Ricatti- needed,84,85 similar to the period that the polystyrene spheres
Bessel functions, N is the particle number density in the so- would last. However, in the case of specific biochemical or
lution, and f共a兲 is the normalized particle distribution func- biological studies, organic molecules and biological cells can
tion that is summed over all p values of particle size. Here, g readily be added to these suspensions to create accurate and
is calculated by: realistic phantoms.86

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 Pogue and Patterson: Review of tissue simulating phantoms¼

Table 4 Absorbers and fluorophores that can be added to aqueous phantoms.

Absorber or
fluorophore Function Limitations Stability References
67,86,156,157
Whole blood Provide realistic Hours to days
tissue spectra and
oxygenation
function
92,97,110,152
Ink Provide nearly Not stable nor Days
flat absorption repeatable unless 共if remixed兲
spectra taken from a
calibrated sample
74,152
Molecular dyes Provide spectra Days to weeks
with wavelength
peaks
158
Fluorophores Compatible with May need to Days to weeks
aqueous avoid aggregation
dissolving effects with
compounds addition of
additional agents
159
Heterogeneities Test Clear enclosures Days
共scattering/absorption tomography and need to be
/fluorescent兲 imaging avoided due to
capabilities light channeling
Used to fill Index of
inclusions in refraction
solid phantoms changes may be
significant for
solid inclusions

2.4 Titanium Dioxide and Aluminum Oxide matrix materials are optimal for different applications, and the
Titanium dioxide 共TiO2兲 powder is perhaps the most common major types are summarized in Table 3. The use of these
choice for scatterering in science and engineering, and this phantom matrix compositions is discussed throughout the re-
stems from its wide availability as the main pigment in com- mainder of the work.
mon white paint. Aluminum oxide or barium oxide powders
are also excellent scatterers, and are commonly used for coat- 4 Aqueous Suspension Phantoms
ing the interior of integrating spheres where exceptionally Water-based phantoms can employ any of the three main scat-
high scatter and low absorption are required. TiO2 powder terers mentioned before lipid, microspheres, or TiO2 power in
comes in several forms and purities, including preformed mi- suspension. The absorption of such phantoms is due mainly to
crospheres, available from Dupont Chemical 共http:// water throughout most of the visible and near-infrared wave-
[Link]/tc/Titanium-Dioxide/兲. lengths. This absorption coefficient is sufficiently low below
The main disadvantage of TiO2 powder is that it resides in 700 nm that it can be ignored 共␮a ⬍ 0.002 mm−1兲, and ab-
suspension in most media, and so settles when not stirred. sorbers can be added to tailor the absorption coefficient and
This is not a problem in resin or agar phantoms once they are spectrum to that of tissue. The water absorption spectrum can
set, but is an issue for aqueous phantoms. Continuous stirring be reliably assumed to match the measurements of Hale and
of the aqueous suspension produces a homogeneous phantom. Querry,87 and an excellent overview of the water spectra
For resin- or agar-based phantoms, mixing for extended peri- available and their conversion between different units is found
ods is also important to ensure that the particles are uniformly at the website [Link] A brief summary of ab-
distributed. Automated stirring for more than 30 min has been sorbers and fluorophores used is listed in Table 4.
a reliable approach for manufacture of reproducible resin
phantoms. Liquid-based stock supplies of TiO2 are now avail- 4.1 Exogenous Absorbers in Aqueous Phantoms
able from Sigma, and these may be a more reliable additive,
as the scattering properties are better controlled than a powder Addition of absorbers and fluorophores to aqueous phantoms
mixed in suspension. has been demonstrated in hundreds of studies, and this phan-
tom design has proven to be extremely valuable in the initial
validation of an imaging/spectroscopy system. Typically the
3 Bulk Matrix Materials for Optical Phantoms goal has been to mimic tissue, so the addition of
The choice of the bulk material for the phantom has perhaps erythrocytes,58,156–164 whole blood, or hemoglobin have all
the largest impact on how the phantom can be used. Different been reported. When attempting to preserve the oxygen bind-

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 Pogue and Patterson: Review of tissue simulating phantoms¼

ing function of hemoglobin, the use of saline rather than dis- used in magnetic-resonance imaging 共MRI兲 and ultrasound
tilled water is important, otherwise the blood cells will lyse imaging for decades,93–95 and they were adopted in optical
and the heme will dissociate from the hemologlobin molecule. tissue phantoms in many laboratories in the mid 1990’s.58,96–99
However, for simplicity, many researchers have chosen to use Agar and gelatin allow inclusion of organic molecules and
ink or molecular absorbing dyes to simulate the absorption of cellular-based constituents, while providing a semisolid object
blood or melanin in tissue. that can have a variety of shapes. Gelatin and agar phantoms
Addition of fluorophores158 has been reported in many have had an equally rich period of development in ultrasound
studies, with hydrophilic molecules used most successfully. imaging, and a large number of papers describe the diversity
Aggregation of certain hydrophobic dyes such as protopor- of phantoms developed here.62,100,101 More recently, the whole
phyrin 9 is possible, but addition of 5% Tween-29 共Fisher area of hydrogels has been studied for biocompatibility and
Scientific, USA兲 as an emulsifying agent has been found to drug delivery applications, and this encompasses most bio-
correct this and result in a monomerized form of the fluoro- logical scaffolds that alter the behavior of water.
phore. The absorption and fluorescence spectra are similar to Polyacrylamide hydrogels have been used as scaffolds for
those observed when the dye is dissolved in a dilute organic collagen and other matrices,102,103 and polyvinyl alcohol hy-
solvent. drogels are reviewed in Sec. 8.1, as they have intrinsic scat-
tering properties as well as being a matrix medium. Polyacry-
4.2 Inclusions and Heterogeneous Lipid Solution lamide hydrogel use has undergone enormous development in
Phantoms biological laboratories for use in electrophoresis and molecu-
An important complication in the use of lipid solution phan- lar separation techniques, yet there are only a few reports of
toms is the choice of container and the possibility of light testing of these matrices as phantom materials.102,103
channeling through the container walls, rather than through
the solution. This is especially problematic over longer dis-
tances and in cases when inclusions or heterogeneities are to 5.1 Scattering Composition
be incorporated in phantoms. Early studies in tomography Since gelatin phantoms are usually used for periods of a day
used containers with thin mylar walls to hold liquid to a week or more and then discarded, they are commonly
inclusions,88,89 but it is apparent that the mylar itself does made with less expensive scattering particles. Construction
perturb the light field. Correction for this effect can be per- with polystyrene microspheres is possible but is quite expen-
formed by filling the inclusion with the same solution as the sive. Use of titanium dioxide 共TiO2兲 power or aluminum ox-
background medium and using this as the “homogeneous” ide 共Al2O3兲 powder is the norm, as they are inexpensive and
reference phantom. However, for smaller inclusions and lower provide a reasonably reliable means to mix a scatterer into the
contrast inclusions, this approach not accurate, and solid liquid gelatin or agar solution while it is cooling. The major
phantoms are preferable. complicating factor in production of these phantoms is the
Light channeling along the top surface of Intralipid over need for careful attention to detail and procedure. For ex-
long distances has also been noted, yet little discussed in pub- ample, the TiO2 scatterers in the phantom readily precipitate
lications. It is important when using this or any optical phan- out, and when ordered in bulk comes in clumpy power form,
tom to shield the surfaces of the phantom properly so that requiring continuous stirring for approximately 20– 30 min to
signals can enter and exit the phantom only at desired loca- ensure homogeneous dispersion in the phantom. Liquid-based
tions. This can be achieved with black masking of the phan- TiO2 is also available and is a reliable method to add con-
tom surfaces, using any opaque acrylic or plastic material. trolled amounts to a solution without the concerns of being
Lipid-based solutions have been used with great success in able to mix and declump the suspension. In addition, TiO2
conjunction with solid phantoms, where holes or channels does settle over time, so the final scattering coefficient of
have been left in the solid phantom to allow dynamic varia- phantoms can vary significantly from one to another. Despite
tion of the heterogeneity optical properties.90–92 This approach careful procedures with TiO2 suspensions, repeated studies in
has been used in many studies to assess detectability of ob- our laboratory show that up to 50% variation can occur. Mak-
jects of differing contrast. This approach allows the use of ing multiple phantoms from a large batch of agar can reduce
contrast-detail analysis as well, to determine the minimum this intersample variation. In addition, the bottom of each
contrast detectable for each size of inclusion in the phantom.90 phantom typically has a large precipitation of TiO2, indicative
There is clearly concern that the transition from solid to liquid of a scattering gradient along the vertical direction. The pre-
matrix involves a change of refractive index, yet experiments cipitated TiO2 is thought to be from larger particles of the
appear to indicate that this is a manageable, if not insignifi- powder, which have higher gravitational force acting on them.
cant, artifact. Increased mixing time reduces the number of these particles.
However, in the end, it is imperative to be able to indepen-
5 Hydrogel-Based Phantoms dently measure the scattering coefficient prior to use in these
types of phantoms, due to inability to exactly predict the scat-
Most substances that encapsulate water as a main component
tering coefficient from a set recipe.
and form a stiff matrix that has limited water mobility are in
the category of hydrogels. Gelatin and agarose are two of the
most common examples, and in biological laboratories there
are hundreds of varieties of these. In this section, agar and 5.2 Additives to Gelatin Phantoms to Improve
gelatin are discussed separately because of their long history Function
as phantom matrix materials. Agar-based phantoms have been Table 5 summarizes some main additives used to improve

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Table 5 Additives that can be used in gelatin/agar phantoms.

Additives Function Limitations Stability References

61,92,98,104,105
EDTA To avoid Days to weeks
Penicillin bacterial growth
共0.5 g / L兲
Sigma Chemical
Co., St. Louis,
MO
98,157
Yeast Remove Hours
Sodium azide molecular oxygen
101,104
Formaldehyde Increase melting Years
temperature
above room
temp.
Requires 0.2%
98,160
Whole blood Provide realistic Oxygen saturation Days
tissue spectra is not easily
changed

Ink Provide flat Not stable nor Days to years

absorption repeatable unless
spectra highly calibrated
and repeatably
mixed
55,96
Organic molecules Matrix holds Stability of each Days
共i.e., glucose兲 most organic molecule must be
compounds assessed
55,58,98
Fluorophores Compatible May need to Days to weeks
with aqueous avoid aggregation
dissolving effects with
compounds addition of
Gelatin provides additional agents
additional
capabilities to deaggregate
160
Heterogeneities Test tomography and Clear enclosures Days to weeks
imaging need to be
capabilities avoided due to
Inclusions can light channeling
be liquid or solid Index of
refraction changes
significantly for
solid inclusions
62,104,105,160
Gadolinium Provide varying Years
Copper Sulphate levels of
magnetic
resonance
contrast
Approx. 1 mg/ ml
57,58
Actinometry Provide measure Unstable over Hours
agents of photochemical long periods of
dose deposition time

the function of gelatin based phantoms. Inclusion of 0.2% agar-based phantoms, but these can become fragile and
formaldehyde in gelatin phantoms increases the melting tem- crumble under applied stress. Gelatin can be ordered from
perature of the gelatin matrix by increasing the crosslinking of different biological origins, and with different bloom levels—
the fibers while preserving the lower Young’s modulus.101,104 increasing the level of bloom results in a stiffer gelatin phan-
This allows the phantom to be used at room temperature with- tom. A pig-skin-based gelatin with a bloom of 175 provides a
out need for refrigeration. This can also be achieved with good stiffness for reliable phantoms.104

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Table 6 Additives that can be used in resin phantoms.

Additive Function Limitations Stability References

23
TiO2 Provide stable Not exactly Years
and calibrated representative of
scatter spectra tissue scatter
spectra
109
Microspheres Provide precise Cost Years
scattering value

Ink Provide flat Not stable nor Years 900NP109

共India ink兲 absorption repeatable unless India90,91,161
共900NP ink兲 spectra highly calibrated

Heterogeneities Holes can be Clear enclosures Years Vessels162,163

embedded in need to be Cylinder90,91
these with avoided due to Spheres113
machining, or light channeling
using preformed Index of
inclusions refraction changes
may be significant
between resin and
aqueous inclusions

Inclusion of biochemically toxic species such as wood pre- scatterers.152,155 The construction of these phantoms requires
servative 共0.01 g / L兲,61 mild acid ethylenediamine tetraacetic mixing a resin and hardener to create a transparent solid resin,
acid 共EDTA兲 at 0.02 g / L,92,104,105 or sodium azide98 provides which typically sets within a few days at room temperature or
a stable phantom that lasts for many days and weeks without within a few hours at elevated temperature. A detailed outline
bacterial growth. The EDTA additive is probably most com- of this procedure can be found at the University College Lon-
mon, because its lower toxicity simplifies handling proce- don website [Link]
dures. Inclusion of penicillin has also been reported for the research/NIRគtopics/phantomគ[Link]. An alternative
same reason.98 While these additives will maintain good bio- recipe can be found at [Link]
logical stability for many days and weeks, they will not keep [Link]. This material can be obtained from a number of
the gelatin from drying out, and the phantoms must be kept manufacturers and in different compositions including: 1.
sealed in airtight enclosures such as plastic bags or containers. Araldite epoxy 共MY753兲 and hardener 共XD716兲, Aeropia
Keeping the phantoms in vegetable oil has also been reported Chemical Supplies, 共Crawley, United Kingdom兲, or 2.
as an excellent way to preserve the water content.104 This Araldite resin 共GY502兲 and hardener 共HY832兲, D. H. Litter
process can provide an intact matrix for years of use of a Incorporated, 共Elmsford, New York兲. Thorough mixing of the
single gelatin phantom, although the other biochemical mol- resin and hardener is critical to obtain a homogeneous volume
ecules included may not last as long as the gelatin matrix that cures in a timely manner. There is significant heat and gas
itself. generated during this process. Degassing of the phantom dur-
Blood has been added to gelatin phantoms55,98 and pro- ing the initial curing process is critical to avoid large numbers
vides an excellent model of tissue spectra in the near infrared, of air bubbles embedded in the phantom. Initial degassing
where the dominant absorbers are hemoglobin and water. In-
during the curing process will cause a massive expansion of
clusion of fat has been reported, but without extensive study
the resin due to the large amount of gas present; however,
of this capability.106
delaying the onset of the degassing, or repeated rapid degas-
For therapeutic study use, these phantoms are ideal, as they
sing and repressurizing cycles, can break the bubbles present
can have the same elastic properties as human tissue and simi-
in the phantom and gradually reduce the phantom volume to
lar thermal properties.107 Inclusion of actinometry agents has
be predominantly resin with little gas.
been demonstrated and used to compare photodynamic dose
A recipe used in our laboratory for a reliable phantom is as
deposition from cw and pulsed laser sources.57,58 Similarly,
follows,90,92 mixing 100 parts Araldite GY502 mixed with 30
measurement of oxygen in phantoms and tissues can be
achieved with fluorescent reporters.108 The potential for bio- parts of the hardener HY 837. Prior to mixing in the hardener,
chemical similarity to tissue, together with the potential for the scatterer and absorber can be mixed into the Araldite thor-
therapy studies, makes these tissue phantoms the best for oughly and degassed to allow a homogeneous mixture of op-
complex tissue geometries and biophysical study. tical properties prior to initiation of the hardening process.
Then when the hardener is added, it can be slowly mixed to
minimize inclusion of air bubbles during the mixing process.
6 Polyester and Polyurethane Resin Phantoms It has been found that 3.5 g of TiO2 powder per liter of resin
Polyester resin phantoms were introduced by Firbank, Delpy, provides a scattering coefficient near 1.0 mm−1 at 800 nm,
and Oda using both TiO223 and polystyrene particle which is proportional to this concentration. Mixing for an

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extended period of time with a magnetic stir bar or an electric Table 7 Additives in RTV silicone phantoms.
mixer is strongly recommended.
In previous studies, the bulk absorption coefficient of the Additive Function Limitations Stability References
medium was set by adding 25⫻ 10−6 liters of ink per liter of 115,116,92,117,164
resin, which was found to increase the absorption coefficient TiO2 Scattering Mixing Years
Al2O3 consistency
to a range between 0.006 to 0.009 mm−1, but different ink
is critical
bottles and solutions will vary significantly, so well calibrated Degassing
and mixed samples of ink stock solution must be used. Par- to remove
ticulate ink absorbers, such as India ink, produce a relatively air bubbles
flat absorption spectrum across most of the visible and near is critical
infrared, as they are composed of carbon particles suspended 150
Molecular Possible Years
in an emulsion. It is important to note that particulate inks absorbers
also scatter light,110 so quantification of the absorption coeffi-
cient of ink in standard spectrophotometers is not possible. 118
Heterogeneities Test Years
Instead, it must be measured in a standard “added absorber” tomography
experiment. Use of molecular absorber inks such as 900NP and imaging
has been firmly established.111–113 Many types of these nonor- capabilities
ganic dyes have been successfully added to this matrix and
provide wavelength-dependent absorption across the near in-
frared, and have no significant scattering coefficient as they this material into biologically relevant configurations with the
are smaller molecules. With consistent procedures, it is pos- stiffness of human tissue has been the main argument for its
sible to obtain a process where phantoms produced succes- use. This was demonstrated by Bays et al. for esophageal
sively have absorption and scattering properties within 10% phantoms115 intended for dosimetry for photodynamic treat-
of their target value. A summary of additives typically used is ment planning. Jiang et al. used this material for breast
in Table 6. phantoms92 to help in calibration of an optical tomography
Polyurethane phantoms were more recently described by system. Lualdi et al. have used these phantoms to study im-
Vernon et al.114 and suggested as a superior alternative to aging of skin lesions using melanin and absorbers that mimic
polyester resin, due to their better compatibility with infrared skin lesions.118 The only major drawbacks of this matrix ma-
dyes to better match the absorbing and fluorescent molecules terial are cost and hardening time, but these are not prohibi-
of tissue. It is stated that these resins provide less bleaching of tive, and a pliable tissue phantom can be quite useful for
the dyes, but extensive testing has not been reported. The applications where the mechanical contact to tissue is impor-
transparency and index change are similar to polyester, mak- tant.
ing these phantoms otherwise quite similar.
8 Novel Materials for Optical Phantoms with
7 Room-Temperature-Vulcanizing Silicone Intrinsic Scattering
Phantoms In addition to the materials discussed in the previous two
Room-temperature-volcanizing 共RTV兲 silicone-based soft sections, there are a number of materials that have been used
phantoms were introduced by Bays et al.150 and Beck et al.116 for phantoms that have intrinsic matrix and scattering proper-
The merits of these phantoms are that they are quickly pro- ties that are interlinked. These are less clearly organized than
duced, have a soft rubber texture similar to stiff tissue, and the previous group, but have properties that could make them
can include nonorganic scatterers and absorbers. The RTV- useful options for certain studies. These range from polyvinyl
based compounds can be obtained from a number of manu- alcohol gels, dough, and teflon, to “engineered” or excised
facturers 共RTV Elastosil 604, Wacker, Munich Germany116,117兲 tissues. Each of these are briefly mentioned in Table 8, and
共Rhodorsil RTV 141, Rhone-Poulenc, France115兲, 共RTV-141, summarized in the following subsections.
Medford Silicone, Medford, New Jersey59兲. Preparation of the
material is similar to the resin-based phantoms described in 8.1 Polyvinyl Alcohol Phantoms
the previous section. Mixing the RTV with its hardener ini- Perhaps the most promising and widely used of these options
tiates a chemical process that solidifies the compound, and are the polyvinyl alcohol gels,119,120 sometimes referred to as
heat and gas generation require pumping under vacuum. This cryogels, due to the fact that their scattering coefficient and
degassing removes the bubbles that are generated when it is stiffness increase with repeated freeze/thaw cycles, allowing
curing. them to be tailored for specific applications. These were origi-
A summary of some additives used with RTV phantoms is nally used in ultrasound and MRI121–123 research, and have
used in Table 7. Beck et al.116 examined ways to embed ab- recently been adopted for photoacoustic tomography, where
sorbers and scatterers into the medium, with the conclusion the combination of elastic and optical scattering properties
that certain stable dyes could be added, but organic molecules makes them ideal for this hybrid imaging approach.124
such as porphyrins were not stable in this polymer. Jiang et al. Kharine et al. report reduced scattering coefficients near
examined controlling stiffness by lowering the hardener con- 0.8 mm−1 after seven freeze/thaw cycles. They also demon-
centration. They showed that the elastic modulus of the phan- strated the ability to create pliable phantoms this way, without
tom could be lowered by a factor of 3, 共from 230 to 80 kPa兲, increased scattering, by including dimethyl sufoxide 共DMSO兲,
making it closer to the stiffness of soft human tissues. Shaping thereby reducing the apparent “whiteness” produced by water

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Table 8 Phantom materials and tissues with intrinsic scattering within the matrix material.

Solid/ Organic
Phantom liquid/ Biologically chemical Inclusions Adjustable Adjustable Index of Recommended
material Permanent flexible compatible compatible possible? absorption scattering refraction use References
119,120,124
Polyvinyl Y F N N Y Y Y 1.36 Heterogeneity
alcohol studies with
gel deformation
Thermal studies
Acoustic studies
共higher cost OK兲

Dough N F Y Y Y Y N 1.35 Heterogeneity N/A

phantom studies
共fixed ␮s⬘兲
127
Engineered N F Y Y Y Y N 1.35 Scientific study
tissue of biochemistry
models and biology
134–136
Ex vivo N F Y Y Y N N 1.35 Reality check ,
134,137–141
tissue scientific studies

freezing in the cycles. This phantom can then be considered a used in tomography phantom studies 共unpublished data兲. The
clear matrix, in which microspheres or TiO2 could be embed- absorption coefficient appears to track linearly with the addi-
ded to create well-controlled optical scattering phantoms tion of higher and higher absorber concentration, as would be
while the elastic properties are set independently. These phan- expected.
toms appear highly promising for use in these hybrid applica-
tions where optical and stiffness properties need to be sepa-
rately controlled. 8.3 Engineered Tissues as Phantoms
These gels can be obtained with average molecular weight
Tissue engineering tools have evolved in the past decade to
of 85 to 140 kDa from Sigma-Aldrich 共USA兲 共catalog num-
the point where structures can be created or grown in culture
ber 36 314-6兲, and are dissolved at a concentration of 20% by
that mimic the structural properties of tissues.108,125–132 These
weight in distilled water while being heated to 90 ° C for 2 h
tissues are most important in situations where the subtle com-
with continuous stirring. After cooling for a few hours to al-
plexities of the biochemistry or thin-layered structure of the
low air bubbles to migrate to the surface, it is then poured into
tissue are simply not well understood, and therefore cannot be
a mold and frozen at −20 ° C for 12 h. This gel is then thawed
fully reproduced by inert tissue phantoms. This issue is espe-
at room temperature and refrozen to produce a stiffer gelatin
cially important in optics for anisotropic scattering due to
matrix, and this can be repeated several times to produce
structures such as collagen matrix133 or muscle fibers, or
stiffer and stiffer phantoms. Without the addition of DMSO,
where the layered sequence of tissues affects the light trans-
the scattering coefficient will increase with each cycle as
port into or out of the tissue.
well.124 This matrix is sensitive to humidity and will likely
Study of epithelial squamous tissues has been a primary
require storage and preparation under humidity controlled
area for this approach,126 mainly due to the possibility of
conditions.
growing epithelial cells on a thin collagen matrix, with me-
dium flowing above and below the culture. This is called a
8.2 Dough-Based Phantoms “raft” culture system, because the cells float on a raft of col-
While the concept of using dough or Play-DohTM may appear lagen. The layered structures of squamous epithelium can be
unscientific, these phantoms have considerable promise be- spontaneously developed, allowing in-vitro study of cellular
cause of their ease of construction, ease of use, and long stor- growth, differentiation, and expression of proteins, so this sys-
age time. Composition of these phantoms is based on a recipe tem is “organotypic” in structure and function. Spectroscopy
for the children’s toy, playdough. The standard mixture can be of these layered structures reveals a biochemical spectrum in
obtained from hundreds of websites, but one such recipe is which the influence of the layered features of the tissue is
250-ml flour, 125-ml salt, 15-ml vegetable oil, 30-ml cream unique and not well modeled by a simple phantom.127,128
of tartar, and 250-ml water. After mixing flour, salt, and oil, While this field is arguably still in its infancy, the potential
slowly add the water. Heat slowly and stir until dough be- is reasonably good for these models to become main stream
comes stiff. When a homogeneous dough ball forms, the mix- tools in molecular imaging studies. As engineered tissues be-
ture is then cooled and left to set. Various absorbers can be come more reproducible between laboratories, this becomes a
easily mixed into the dough as well, with India ink being used viable option. Another rationale for the use of these structures
successfully. This composition leads to a pliable phantom is as a replacement for animal studies. Alternatives to animal
with ␮s⬘ = 1.6 mm−1 at 800-nm wavelength. Repeated mix- models are usually welcome in laboratories as long as the
tures had similar scattering coefficients, and were successfully model is a true representation.127,133

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8.4 Ex-Vivo Tissue discrepancies in the absolute values obtained. Intersystem

While ex-vivo tissue is not technically a phantom, its wide- comparison measurements have been completed by several
spread use in tissue spectroscopy and imaging merits some laboratories, and routinely show at best a 10 to 15% agree-
mention. Because of the biological complexity of the absorp- ment between groups,146,147 with some measurements having
tion and fluorescence spectrum of tissue, as well as the com- close to 50% disagreement. Clearly the status of repeatability
plexity of mimicking layered and scattering structures in absorption and scattering properties is far from ideal at the
accurately,55 it is often useful to avoid phantoms and simply current moment, mainly due to a lack of a gold standard mea-
use excised tissue.71 This has been common in light transport surement system, a standardized model phantom to compare
studies, especially where the goal has been to study transport to, and systematic variation in the preparation of phantoms.
and the anisotropy that can occur in structured tissues.134–136 Standardized phantoms to establish the accuracy and re-
In diffuse imaging applications, there has been widespread peatibilty of newly developed instruments are an area that
use of chicken or bovine muscle as an ex-vivo tissue to test should take on a new level of priority in the scientific com-
transmission measurements134,137–141 as a reality check on how munity, as optical imaging and spectroscopy systems achieve
the modeling or measurement system performs in real tissue. regulatory approval for marketing and clinical use. It is gen-
While phantoms are useful, there is always the concern that erally agreed that polyethylene or polyurethane phantoms are
the phantom does not really mimic the tissue properties well, needed with well-controlled and repeatable optical properties
and an ex-vivo sample can serve as a useful intermediate prior to calibrate and test the performance of such systems. Unfor-
to initiating human or animal studies. Chicken breast tissues tunately at this time, commercial production and distribution
are often used, as they are extremely low in blood concentra- of these phantoms is not commonly available, although sev-
tion and have low scattering coefficient values, providing a eral researchers have taken the responsibility of distributing
tissue with exceptionally good light penetration.141 Bovine recipes in an attempt to provide uniformity to the field.146,147
muscle or liver offer increasingly darker pigmentation to test This process needs to continue, and ultimately, as in all clini-
penetration, and can be quite homogeneous as well.41,42 cal radiology systems, a company should produce phantoms
It is likely true that the bulk scattering coefficient may not with well controlled and known optical properties in different
be altered significantly when the tissue is excised, but it is geometries. This is similar to what is available for optical
certainly true that the absorption due to blood will decrease as reflectance standards, but would have independent validation
the blood volume decreases after removal. Also, energetic as is currently available for CT, mammography, or MRI phan-
changes associated with NADH, FAD, and hemoglobin oxy- toms approved by the American College of Radiology.
genation will also change as oxygen is consumed and all tis- This survey provides the first steps in summarizing
sue will become ischemic within several seconds of removal. progress in the field. The uses of optics are so diverse that it is
Preservation of the tissue oxygen and energy level state can not likely an exhaustive review, but the references in near-
only be achieved with cryogenic freezing of the tissue before, infrared spectroscopy and imaging are comprehensive and
during, or immediately after the removal process.142–144 For should prove useful. Multimodality phantoms are an emerging
optical therapy studies, excised tissue may preserve the ther- field, and a significant number of developments are likely in
mal properties of the tissue and offer a good model of non- this area as optical imaging and spectroscopy become utilized
perfused organs such as the cornea 1.145 However, the heat alongside and within standard clinical imaging systems. This
convection due to blood flow is lost ex vivo, and ex-vivo tissue summary should logically be followed by a push toward de-
is not a good model for long term heat distribution studies in velopment of standardized or recommended phantoms based
perfused tissues. on specific applications, and eventually by commercial
products.

9 Conclusions Acknowledgments
This summary of phantoms and phantom materials is an at- This study was supported through grants PO1CA84203,
tempt to identify common themes in a field that has a large PO1CA80139, RO1CA109558, PO1CA43892, and a grant
diversity of applications and methods distributed throughout from the National Cancer Institute of Canada. The authors
hundreds of research laboratories. Major problems exist in wish to gratefully acknowledge assistance and collaboration
tissue phantom work due to the lack of uniformity and the in phantom making and analysis over many years with col-
lack of a “gold standard” for comparison. However, the leagues at the Juravinski Cancer Center 共Hamilton, Ontario,
strengths and weaknesses of phantom technology are best dis- Canada兲, Princess Margaret Hospital 共Toronto, Ontario,
cussed in terms of the application, as mentioned at the begin- Canada兲, Wellman Center for Photomedicine at the Massachu-
ning of this work. setts General Hospital 共Boston, Massachusetts兲, and Thayer
For application of phantoms in validating theoretical or School of Engineering at Dartmouth College 共Hanover, New
experimental systems, optimal choices are based on well cali- Hampshire兲.
brated and known quantities, and so microspheres or In-
tralipid are excellent choices, and allow the use of aqueous
emulsions or gelatin-based solid phantoms. This approach has References
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