J. Biophotonics 4, No. 11–12, 773–787 (2011) / DOI 10.1002/jbio.

201100062
Journal of

BIOPHOTONICS

REVIEW ARTICLE
A review of in-vivo optical properties of human tissues
and its impact on PDT
Julia L. Sandell and Timothy C. Zhu*

Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce St/2 Donner, Philadelphia, PA, 19104, USA

Received 14 July 2011, revised 7 September 2011, accepted 8 September 2011

Published online 10 October 2011

Key words: in-vivo optical properties, light propagation, PDT, laser-tissue interaction

A thorough understanding of optical properties of biolo-

gical tissues is critical to effective treatment planning for
therapies such as photodynamic therapy (PDT). In the
last two decades, new technologies, such as broadband
diffuse spectroscopy, have been developed to obtain in
vivo data in humans that was not possible before. We
found that the in vivo optical properties generally vary
in the ranges ma ¼ 0:031:6 cm1 and m0s ¼ 1:240 cm1,
although the actual range is tissue-type dependent. We
have also examined the overall trend of the absorption
spectra (for ma and m0s ) as a function of wavelength with-
in a 95% confidence interval for various tissues in vivo.
The impact of optical properties on light fluence rate is
also discussed for various light application geometries
including superficial, interstitial, and within a cavity.

Relative fluence rate, f=fair , versus meff for various light

source geometries for m0s ¼ 10 cm1 .

1. Introduction ties of human tissue can differ significantly from that

Laser light has been increasingly used in many bio-
medical applications, such as photodynamic therapy
(PDT) and laser interstitial thermal therapy (LITT).
For these medical applications, it is essential to un-
derstand the light propagation. A database of in-vivo
optical properties (absorption coefficient and re-
duced scattering coefficient) of human tissue, is cru-
cial to allow accurate calculations of fluence rate in
and around treatment areas. In vivo optical proper-
of the ex vivo human tissue samples [1–10]. It can
also be different from in-vivo animal data. Zhu et al.
found that the effective attenuation of canine pros-
tate is two times greater than that of human prostate
[11]. Great advances were made in the last two dec-
ades to determine the in vivo optical properties in
humans in a variety of organs. This paper reviews
the existing data in the literature since the previous
reviews [3, 10] to greatly expand the human in vivo
portion of the summary, along with the experimental

* Corresponding author: e-mail: tzhu@mail.med.upenn.edu

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 Journal of
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methods and theories used to determine the optical
properties. The data summarized here covers a range
of wavelengths and measurement methods.
2. Light transport equations
The general radiative transport equation describing
light transport through a turbid medium can be [12]:
1 @L ^  rLðr, W, tÞ ¼ ðm þ m Þ Lðr, W, tÞ
þW a s
v @t
ð
þ ms pðW, W0 Þ Lðr, W0 , tÞ dW0 þ Sðr, W, tÞ
4p
(1)
Here L is the irradiance defined as the radiant
power per unit solid angle about the vector W ^, W^
represents the direction the incident light is traveling
in within the tissue, S(r, W, t) describes the light
source (measured in joules), and p(W, W0 ) is the
phase function, which, when integrated over 4p, is
equal to one; v is the speed of light in the medium.
The absorption coefficient, ma , is defined as the
probability of absorption per unit distance. Similarly,
ms is the probability of scattering per unit distance.
Generally, the exact form of the phase function is
complex [13–16] and is often taken as the Henyey–
Greenstein (HG) phase function and a single pa-
rameter g, which is the average cosine of the phase
function [17]. g can vary from 1 to 1 but the tissue
scattering is often anisotropic (with g  0.7–0.9).
Equation (1) can be used to determine the radiance
for known spatial distribution of the absorption and
scattering coefficients. Several approximations can
be made to simplify Eq. (1) depending on the type
of irradiance and the optical boundary conditions
[18]. For a more detailed review of phase function,
the readers are referred to [13–16].
The diffusion approximation is often made to
solve Eq. (1) by expanding L(r, W, t) in terms of
spherical harmonics Yn, m with only the first two
terms being considered. The first term in the expan-
sion can be related to the fluence rate of the incident
light, defined as the radiant power incident on an in-
finitesimal sphere divided by the cross-sectional area
of that sphere [18, 19]:
Ð
Fðr, tÞ ¼ Lðr, W, tÞ dW ð2Þ
4p
the diffusion equation can be expressed as [18]:
1 @F ðr, tÞ
¼ r  Dr Fðr, tÞ  ma Fðr, tÞ þ Sðr, tÞ
n @t
ð3Þ
where D ¼ ð1=3Þ ðma þ m0s ) is the diffusion constant
and m0s ¼ ms ð1  g) is the reduced scattering coeffi-
# 2011 by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
J. L. Sandell and T. C. Zhu: Review of optical properties
cient. The diffusion approximation gives a suffi-
ciently accurate description of light transport in tis-
sue in the near infrared (NIR) region. As a result,
we will use it as a gold standard for light transport
modeling in this review. The necessary optical prop-
erties then become ma and m0s .
In some instances, diffusion theory fails at short
source-detector distances (on the order of 1 mm)
[20]. Consequently, more accurate approximation
methods can be applied to the radiative transport
equation. These methods range from higher-order
analytic solutions using the spherical harmonics [20–
22] to Monte Carlo (MC) simulations [19, 23–26].
Working from Eq. (1), a PN approximation is applied
by first expanding the angular quantities of Eq. (1)
in terms of spherical harmonics and then writing the
phase function as a series of Legendre polynomials
[20]. MC simulations is a statistical method, which
uses the probabilities of scattering and absorption
within the medium and at the medium boundary for
photon transports in incremental steps [27]. The
photon transport is modeled by probability distribu-
tions as photons complete their random walk in a
medium. Simulation geometries can include the sim-
ple homogeneous plane or more complex geometries
such as multilayered systems and spherical cavities
[28]. MC is a rigorous method but it can be expen-
sive in computation time.
3. Experimental methods to determine
in-vivo optical property
Several different methods (either superficial or inter-
stitial) can be used to determine the optical proper-
ties in vivo, which can be invasive or non-invasive.
Generally a non-invasive technique is preferred as
the in-vivo optical properties of tissue are highly sen-
sitive to changes in environment. Most modern
methods of non-invasive optical property measure-
ments use absorption spectroscopy; depending on
the time variance of the light source, it can be cate-
gorized as continuous wave (CW), time-of-flight
(TOF), or frequency resolved spectroscopy. Most
theoretical analyses use the diffusion approximation
so only ma and m0s are obtained.
3.1 Continuous wave absorption spectroscopy
3.1.1 Reflectance spectroscopy
Continuous wave (CW), spatially-resolved diffuse
reflectance absorption spectroscopy can be obtained
from a contact probe to collect reflected light from a
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J. Biophotonics 4, No. 11–12 (2011) 775

Where F is the fluence rate, D is the diffusion con-

stant (see Eq. (3)), A is a constant that depends on
the Fresnel reflectance at the surface of the bound-
ary and can be determined from the indices of re-
fractions and the numerical aperture of the incident
light [18, 20]. F(r, z ¼ 0) in Eq. (4) is the fluence
rate at the surface [37–38]:
 m r1 
1 e eff emeff r2
Fðr; zÞ ¼  ð6Þ
4pD r1 r2

Rf is the reflected flux exiting the surface from the

tissue [18, 37]:
   
1 1 emeff r1 1
Rf ðrÞ ¼ meff þ þ þ 2zb
4pm0t r1 r12 m0t
  
1 emeff r2
 meff þ ð7Þ
r2 r22

where m0t ¼ ma þ m0s , zb ¼ 2AD, z is the depth of the

Figure 1 (online color at: www.biophotonics-journal.org)
Schematics of broad-band diffuse reflectance spectroscopy
measurement, and r1 and r2 are the radial distances
(BDRS). Pencil beam light source was incident from the from the detector to the two point sources ðz ¼ 0
left fiber. The photons are randomly scattered (depicted and z ¼ 2zb Þ. Using reflectance measurements, ma
by orange dots) and absorbed (depicted by green dots) as and m0s can be found within 5–15% [38].
they travel through tissue. The absorbed photons are
trapped in the tissue while the scattered photons continue
to either be absorbed or scattered and ultimately detected
by the detector fiber located at a distance r from the inci- 3.1.2 Transmittance (or interstitial)
dent light source.
spectroscopy

tissue surface (Figure 1). The measured reflectance Transmittance spectroscopy is often applied intersti-
can be used to determine ma and m0s by fitting the tially to invasively determine the tissue optical prop-
data with the calculations [29–36]. The reflectance, erties in vivo. Compared to reflectance spectroscopy,
in the diffusion approximation, can be expressed as it is easier to solve the diffusion equation because of
[37]: the absence of the complicated boundary conditions.
ð Transmittance is measured by placing a light source
1
RðrÞ ¼ dW ð1  Rfres ðqÞÞ fiber through a biopsy needle and inserting the nee-
4p dle into the tissue to be studied. A detector fiber is
2p
  then placed some distance away within the tissue to
@F ðr; z ¼ 0Þ measure the light that is transmitted through. The
 Fðr; z ¼ 0Þ þ 3D cos q cos q
@z fluence rate for a point source can be expressed as
¼ C1 Fðr; z ¼ 0Þ þ C2 Rf ðrÞ ð4Þ [2, 39]:

where Rfres(q) is the Fresnel reflection coefficient as 3m0s meff  r

a function of incident angle q, C1 and C2 are con-
stants which depend on the index of refraction, the
boundary conditions, and the numerical aperture of
the optical fiber (C1 ¼ 0:118; C2 ¼ 0:306 for air-tis-
sue interface, n ¼ 1:4Þ [18, 20, 37].
Haskell et al. [18] provided a comprehensive re-
view of the boundary conditions. The most common
(partial current) boundary condition, can be ex-
pressed as [18]:
F þ 2A D^
n  rF ¼ 0
f=S ¼ e ð8Þ
4pr
where r is the radial distance away from the source;
j is the absolute light fluence rate, and S is the
source strength. The detector can be placed at vary-
ing distances from the light source within the tissue
[33]. Data can be fit to Eq. (8) to extrapolate ma and
m0s [33] (Figure 2). Equation (8) can be modified to
account for the effect of tissue heterogeneity and
ð5Þ source weight distribution from a linear source [40].

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3.2 Time of flight absorption spectroscopy
Another form of measurement is time-of-flight ab-
sorption spectroscopy, which measures photons di-
rectly following an input impulse of light. Photons
incident on a scattering medium will arrive at the de-
tector at different times. This distribution of the
time-of-flight can be measured with picoseconds
pulsed lasers. The speed of these photons in tissue is
given by v ¼ c=n where c is the speed of light in va-
cuum and n is the index of refraction of the tissue
sample [27]. Note that for soft tissues, this value of n
is in the red and near-infrared part of the spectrum,
which corresponds to TOF distributions ranging
from 100 ps to 1 ns, depending on the optical path
hli
length hli, hti ¼ [41, 42]. By assuming an infinite
v gular frequency and Ms is the source modulation am-
homogeneous medium with a point source, one
can express the local fluence rate as:
fðr; tÞ ¼ vð4pDvtÞ3=2 exp ðr2 =4Dvt  ma vtÞ [43].
Under these assumptions, ma and m0s become func-
tions of the time of maximal signal and the decay
constant at long times of the light distribution curve
[44]. From this we find that the absorption coeffi-
cient can be taken directly from the final slope of
this curve. TOF measurements offer the advantage
of requiring only relative measurements to extrapo-
late optical properties from the temporal variation
of the fluence rate [41]. One single MC simulation
can be used to extrapolate optical properties using
TOF spectroscopy [23]. A further advantage of TOF
spectroscopy is the ability to assess structural proper-
ties of the medium [41]. However, the high cost of
high-time resolution equipment is a disadvantage of
this particular technique.
# 2011 by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
J. L. Sandell and T. C. Zhu: Review of optical properties
Figure 2 (online color at:
www.biophotonics-journal.org) Ex-
trapolation of optical properties
from measured transmission data
from a point source. The measured
data (symbols) are fitted with a
best-fit using the optical properties
according to Eq. (8) (line); these
data are displayed in the lower
left-hand panel. Taken from [33].
3.3 Frequency resolved spectroscopy
Frequency domain spectroscopy uses a sinusoidal
modulated light source (with a typical frequency
range of 100 MHz to 1 GHz) to detect a phase
shift and amplification from the incident light [18,
45–49]. After light from a sinusoidal light source tra-
vels through a scattering medium, the detected light
will still be sinusoidal, but it will be delayed in time
due to scattering along with a reduced amplitude.
The resulting observed phase shift, q, can be ex-
pressed in terms of the frequency f, the speed of
light v, and the mean path length l of the photons,
q  2pfl=v ¼ wl=v, in the limit of high frequencies
[50]. Equation (3) can be solved for j using a sinu-
soidal source, Sðr, tÞ ¼ Ms cos ðwtÞ where w is the an-
plitude. By solving Eq. (3) for this source, light
fluence rate can be expressed as a function of the
phase q and modulation amplitude M for a point
source as fðr, wÞ ¼ M cos ðwt þ qÞ=ð4pDrÞ, where
qðr, wÞ ¼ rmeff ð1 þ ðw=ma vÞ2 Þ1=4 sin ð1=2 tan1
ðw=ma vÞÞ, M ¼ Ms exp ðrmeff ½ð1 þ ðw=ma vÞ2 Þ1=4 cos
ðð1=2Þ  tan1 ðw=ma vÞÞ  1Þ [51]. This method al-
lows us to detect weak signal during CW photody-
namic therapy due to the frequency modulation. It
requires less source-detector separations to recover
optical properties due to the additional information
from the phase shift. The key advantage offered by
frequency resolved spectroscopy is that it is less ex-
pensive than TOF techniques that can be practically
applied over a range of wavelengths and frequencies
[51, 52].
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J. Biophotonics 4, No. 11–12 (2011)
4. Summary of in-vivo optical properties
in humans
The absorption coefficient varies greatly over the
visible spectrum, while the scattering coefficient of
tissue decreases monotonically as the wavelength in-
creases [12]. The presence of chromophores affects
the absorption coefficient. Chromophores are tissue
components which absorb light and, in the visible
part of the spectrum, are mainly in the form of he-
moglobin and melanin. Hemoglobin is responsible
for carrying oxygen from the lungs to the rest of the
body. The absorption spectrum for deoxy-hemoglo-
bin and oxy-hemoglobin are distinctly different, thus
resulting in difference in total absorption as a func-
tion of oxygen saturation [53–58]. The absorption
spectrum of oxy-hemoglobin peaks between 400 nm
and 600 nm and deoxy-hemoglobin peaks between
400 nm and 850 nm (Figure 3) [53–61]. Comparing
this to the absorption spectrum of water (which
peaks between 900 nm and 1100 nm, Figure 3), [56–
58, 61] the dominant absorbent in tissue for PDT is
hemoglobin, which is performed in the near infrared
region (NIR). Another common source of light ab-
sorption is melanin, a biological pigment, which ab-
sorbs light in the wavelength range 330 nm to about
700 nm (Figure 3) [62–66], with a particularly high
absorption rate in the ultraviolet part of the spec-
trum. The absorption coefficient, subsequently, is un-
ique for condition and can be used to extrapolate
the concentrations of each absorbent (oxy-hemoglo-
bin, dexoy-hemoglobin, melanin, water) from the
diffuse absorption spectrum measurements.
Figure 3 (online color at: www.biophotonics-journal.org) Mo-
lar absorption coefficients of common absorbents in tissue:
oxy-hemoglobin, deoxy-hemoglobin, melanin, and water.
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The scattering seen in tissue is due to the pre-
sence of biological cells and is dependent on the cell
morphology [67, 68]. Scattering can be caused by the
cell nuclei, mitochondria, lysosomes, and the Golgi
apparatus [68]. At small incident angles the cells
themselves are responsible for scattering, whereas at
larger incident angles the nuclei of cells may be re-
sponsible for the scattering [67, 68]. The indices of
refraction in cells must be considered for the scatter-
ing [68–70]. To model this scattering, Mie theory
[71–75] is often used, treating the scattering particles
as individual spheres distributed either monodisper-
sely or polydispersely with an incident planar elec-
tromagnetic wave [29, 30, 70–76], as a function of
distance between the observers and particle, the
scattering angle, the refractive index of the particle,
and the diameter of the particle [67, 77].
Table 1 lists the measurements of optical proper-
ties of in vivo (ma and m0s ) human tissue at room tem-
perature (22  C) for treatment wavelengths com-
monly used for PDT; the method used to obtain the
optical properties is also listed, as explained in Sec-
tion III.
Figure 4 presents the spectra of human tissues in
vivo for ma and m0s as a function of wavelength. The
data was taken from the literature reviewed here
and for respective tissue and optical properties, and
were fitted with a series of best-fit lines (R2 > 0:90)
using the software package Stata. The data was then
compared to the resulting fit and a 95% confidence
interval was obtained from this comparison (denoted
by the gray band seen in Figure 4a–i). A p-value
was calculated for all data at a particular wavelength
(for breast tissue: ma (p < 0.001) and m0s (p < 0.001);
for skin: ma (p < 0.05) and m0s (p < 0.001); for pros-
tate tissue: ma (p ¼ 0.001) and m0s (p < 0.001; for
small bowel tissues: ma (p < 0.01) and m0s (p < 0.01);
and for bone tissue: ma (p < 0.01) and m0s
(p < 0.001)). For wavelengths l > 690 nm where the
absorption of hemoglobin is no longer dominant, tis-
sue optical properties will be affected strongly by
the absorption of photosensitizer. As a result, the
spatial distribution and dynamic photobleaching of
the photosensitizer will affect the in vivo optical
properties. For example, the peak observed at
740 nm in prostate tissue is caused by the presence
of a photosensitizing drug, motexafin lutetium. The
result of this analysis is the overall trend in ma and m0s
as a function of wavelength for particular human tis-
sues in vivo observed in the literature.
The data presented here focuses on bulk tissues
within the human body. For superficial measure-
ments for tissues such as skin, a multi-layered geo-
metry of tissue optical properties must be considered
to extrapolate tissue optical properties correctly.
Layered tissues that have different regions of optical
properties experience photon propagation differ-
ently than bulk tissues. A two-layer model is often
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Table 1 In vivo optical properties at commonly used treatment wavelengths for PDT.

Tissue l (nm) ma (cm1) m0s (cm1) Experimental References

Method
4
Bladder 532 0.27–0.71 1.28–3.30 [108]
4
630 0.28–0.76 2.5–6.37 [108]
1
Bone 650 0.09–0.14 12.5–15.8 [109]
1
760 0.07–0.09 11.9–14.1 [109]
4
Brain 420 0.01–3.51 18.75–55.83 [108]
4
532 0.02–3.84 0.10–46.3 [108]
4
630 0.02–0.50 3.72–21.97 [108, 110, 111]
1, 2
760 0.11–0.17 4.0–10.5 [6, 112]
2
780 0.078–0.089 8.42–9.16 [8]
1, 4
Breast 660 0.037–0.110 11.4–13.5 [113–118]
1, 4
760 0.031–0.10 8.3–12.0 [115, 116, 118–121]
1, 4
900 0.096–0.29 3.33–5.86 [9, 115, 118, 122]
4
Tumor 530 0.60–0.86 28.0–32.1 [123]
2
690 0.070–0.10 14.7–17.3 [124]
2
895 0.068–0.102 12.4–13.1 [124]
Bowel
4
Small 630 0.19–0.21 8.95–10.05 [35, 76]
4
Large 630 0.12–0.18 10.11–10.42 [35, 76]
4
Diaphragm 661 0.15–1.08 9.65–21.7 [125]
4
Heart 630 0.03–1.55 17.56–75.06 [126]
4
661 0.12–0.18 5.22–90.80 [125]
4
Liver 630 1.15–1.56 21.6–30.4 [35, 76]
4
Lung 630 0.16–1.36 1.07–83.81 [126]
4
661 0.49–0.88 21.14–22.52 [125]
4
Pericardium 630 0.13–0.33 13.0–21.9 [35, 76]
4
Prostate 630 0.05–1.0 3.41–17.02 [127, 128]
4
650 0.14–0.61 5.24–22.68 [128–130]
1, 3
672 0.09–0.72 7.1–25.0 [44, 128, 129, 131]
3
732 0.09–0.72 3.37–29.8 [39, 129, 131]
2, 3
762 0.11–1.6 1.2–40.0 [11, 129, 131–133]
1, 4
Skin 630 0.05–1.11 2.26–20.95 [34, 35, 126, 134, 135]
4
661 0.51–0.64 2.24–5.77 [116, 125, 136]
1
800 0.16–0.23 6.80–9.84 [116, 137, 138]
1
Time of flight absorption spectroscopy.
2
Frequency Resolved Spectroscopy.
3
CW Absorption Transmittance Spectrsocopy.
4
CW Absorption Reflectance Spectroscopy.

considered [19, 78, 79], where, if the thickness of the
first layer is known, the absorption coefficients of
both layers in the system can be determined. The
two-layer model, however, falls short in that is still
assumes homogeneous, bulk tissues rather than an
inhomogeneous layered structure. Multi-layer struc-
tures are considered [80, 81] for greater accuracy in
modeling light propagation in skin.
5. The effect of tissue optical properties
on light propagation
Photodynamic therapy is inherently a dynamic pro-
cess. There are three principal components: photo-
sensitizer, light, and oxygen, all of which interact
and vary on timescales relevant to a single treatment
[82]. The distribution of light is determined by the
light source characteristics and the tissue optical

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(a) (b)

(c) (d)

(e) (f)
Figure 4a–f

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 Journal of

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780 J. L. Sandell and T. C. Zhu: Review of optical properties

(g)
(h)

(i) (j)
Figure 4 Absorption and Scattering coefficients of human tissue in vivo versus wavelength for breast (a, b); skin (c, d);
prostate (e, f); small bowel (g, h); and bone (i, j). The grey shaded region is the range of ma and m0s with a 95% confidence
interval based on review of the literature.

properties. The tissue optical properties, in turn, are
influenced by the concentration of photosensitizer
and the concentration and oxygenation of the blood.
The distribution of oxygen is altered by the photody-
namic process, which consumes oxygen and may al-
ter blood flow [83]. Finally, the distribution of photo-
sensitizer may change as a result of photobleaching,
the photodynamic destruction of the photosensitizer
itself.
From a physics point of view, the explicit PDT
dose is defined as the light energy deposited to
photosensitizer, i.e. it is proportional to the product
of the absorption coefficient of the photosensitizer
ðt
jðtÞ
and light fluence: D ¼ ecðtÞ dt. Where e is the
hn
0
extinction coefficient and c is the photosensitizer
concentration [84]. PDT dose calculated in this way

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J. Biophotonics 4, No. 11–12 (2011)
is a good predictor of outcome if one is operating in
a drug- or light-limited regime when there is ample
oxygen supply [85]. Thus the direct link of tissue op-
tical properties and PDT dose is the light fluence
rate and the impact of in-vivo optical properties on
j will be discussed here.
5.1 Superficial application
For tumors located in accessible regions such as on
the surface of the skin [86], superficial light applica-
Figure 5 (online color at: www.biophotonics-journal.org)
MC-calculated f=fair as a function of tissue depth (a) and
beam radius (b). The f=fair was calculated for varying
beam radii and incident angles (solid line for normal,
dashed lines for 45 ). Note the exponential decrease with
increasing depth. The f=fair becomes a constant after the
beam radius reaches 2 cm. Data taken are from Ref. [87].
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tion is clearly the most practical. In such situations,
the treatment area is considered a semi-infinite slab
of tissue in the presence of the air-tissue boundary.
Several factors which affect light fluence are light
source beam size, incident angle, and the optical
properties [3, 86–91]. Light fluence rate in a circular
field ranging in sizes from 0.25 cm to 8 cm (in radius)
and normally incident on the tissue surface has been
studied using MC simulation [86]. Because of the
backscattering from the boundary the fluence rate
beyond the boundary in air can be greater than that
without the turbid medium [86]:
f=fair ¼ ð1 þ 2Rd Þ ð9Þ
where [86, 92]
a0 pffiffiffiffiffiffiffiffiffiffiffi0 ffi pffiffiffiffiffiffiffiffiffiffiffi0 ffi
Rd ¼ ð1 þ eð4=3Þ A 3ð1a Þ Þ e 3ð1a Þ , ð10Þ
2
where a0 ¼ m0s =ðma þ m0s Þ, A ¼ ð1 þ rj Þ=ð1  rf Þ
(where rj and rf are functions of the indices of re-
fractions, A ¼ 2.9 for air-tissue interface) [18]. The
fluence rate in tissue can be expressed as [86, 93]:
fðrÞ ¼ fair k  emeff r ð11Þ
Where k is the backscatter coefficient which can be
determined by comparison with MC simulation
(numerically k ¼ 3 þ 5:1Rd  2 e9:7Rd for air-tissue
boundary) [94]. Good agreements are observed
among the measurements, an empirical solution and
the MC simulation [2, 87, 94, 95]. f=fair (see Figure 5a)
will increase sharply at the water-tissue boundary
and then exponentially decrease with increasing
Figure 6 (online color at: www.biophotonics-journal.org)
Relationship between the diffuse reflectance Rd and opti-
cal properties. The symbols are measurements and the
lines are theoretical calculations described in the text.
Data are taken from Ref. [92].
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782 J. L. Sandell and T. C. Zhu: Review of optical properties

(b)
(a)

(c) (d)

Figure 7 Fluence rate, normalized to in-air fluence rate fair, versus meff for linear (solid line), point sources (dashed line)
inside an infinite medium, planar light sources (dotted line) on a semi-infinite medium below an air-tissue interface, and
point source with multiple scattering (MS) (dash-dotted line) inside a spherical cavity of 10 cm radius at 0.5 cm from the
light source (for point or linear sources) or 0.5 cm depth in tissue (planar or MS point sources) for m0s : (a) 2.0 cm1, (b)
10.0 cm1, (c) 20 cm1. See text for the definition of fair. (d) f=fair within a spherical cavity at air-tissue boundary for
m0s ¼ 2:0 cm1 (dotted), 10.0 cm1 (dashed), and 20.0 cm1 (solid) using Eqs. (10) and (12).

depth and will significantly decrease with decreasing
beam radius. The light fluence rate, as a function of
beam radius and depth in tissue will drop substan-
tially for small light fields as compared to broad
beam fields (see Figure 5b). Significant differences
in f=fair occur between normal and oblique inci-
dent beams, when the beam radius is less than 2 cm
[87].
Figure 6 shows the relationship between the light
fluence rate at tissue surface and the optical proper-

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J. Biophotonics 4, No. 11–12 (2011)
ties. For a known reduced scattering coefficient m0s ,
f=fair depends on the effective attenuation coeffi-
cient meff directly. This optical properties dependence
is even more pronounced inside tissue where the ef-
fective attenuation coefficient meff determines light
penetration (Eq. (11)), as shown in Figures 7(a)–(c)
as dashed line for light fluence rate per incident light
fluence rate in air at 0.5 cm depth. (Notice the in-air
light fluence rate fair is calculated as incident power
per unit area.) The light fluence rate decreases with
increasing effective attenuation coefficient meff for a
known reduced scattering coefficient, m0s . In clinic
settings, the tissue optical properties are often het-
erogeneous, thus one needs to further account for
the effect of tissue heterogeneity by solving the dif-
fusion equation (Eq. (3)) directly.
5.2 Interstitial application
Interstitial application, is better suited for bulk tis-
sues because superficial applications have limited
light penetration [96, 97]. Optical fibers are placed
directly in the tissue, and consequently an interstitial
measurement does not have the tissue-air boundary
problems to contend with as superficial application
does. The light distribution for any light source geo-
metry can be calculated from that of a point source.
Equation (8) relates the light fluence distribution
and optical properties for a point source. As ex-
pected the fluence rate is greatest at points closest to
the light source [96, 98] and thus is position depen-
dent. Figure 7(a)–(c) compares the light fluence rate
(at 0.5 cm from source or 0.5 cm depth and normal-
ize to the incident light fluence rate, fair ) depen-
dence on meff (inverse of the optical penetration
depth) for different light source geometries (point
source, infinitely long linear source, planar sources
incident on semi-infinite tissue medium, and MS
point source inside a 10 cm sphere) and for m0s be-
tween 2 and 20 cm1. The incident light fluence rate
(or in-air light fluence rate) is defined as power per
spherical area S/4pr2 for point and MS point sources,
power per cylindrical area or s=2pr for linear source
(s is the power per length), and power per incident
area S/A for planar source. It is clear that the light
fluence rate decreases with increasing meff . The light
fluence rate in tissue can be significantly higher (up
to 45 folds) than that calculated based on the energy
released per area fair depending on in-vivo tissue
optical properties.
Several interstitial studies [96, 97, 99–101] con-
sider how knowledge of optical properties (ma and
m0s ) affects the fluence rate. Zhu et al. [99] points out
that the heterogeneity of ma and m0s contribute to var-
iations in fluence rates at similar depths from the
point source. Li et al. [40] compares different algo-
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REVIEW
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783
rithms for interstitial application, while accounting
for tissue optical heterogeneity [40]. A main factor,
which affects the accuracy of the determined fluence
rates in tissue, is the heterogeneous optical proper-
ties distribution. Studies [97, 100] conclude that opti-
mization of treatment planning is ineffective without
knowledge of the heterogeneity of ma and m0s .
5.3 Intracavitory application
In intracavitory application, light is applied inside a
cavity of a surrounding tissue boundary, e.g., in
pleural and bladder cavities. Within the cavity, light
is multiple-scattered by the cavity walls and causes
the total fluence rate to be increased by as much as
a factor of seven larger than the fluence rate of the
non-scattered light from the isotropic source itself
[102–104]. Thus, we must account for this increase
in fluence rate, referred to as the integrating sphere
effect (ISE). The light fluence rate from scattered
light inside the cavity can be expressed as:
4S Rd S
fs ¼  ¼ b ð12Þ
4pr02 1  Rd ð1  f Þ 4pr02
Where Rd is the diffuse reflectance (Eq. (10)), r0 is
the radius of the cavity. f is the fraction of the area
of the opening of the integrating sphere and the to-
tal surface area1, and b ¼ 4Rd =ð1  Rd ð1  f ÞÞ is the
reflection factor, which describes how much the scat-
tered light is increased and is dependent on tissue
optical properties [104]. Determining this value of b
is a key for fluence rate calculations for intracavitory
geometries. The diffuse reflectance depends on both
the indices of refraction mismatch and the optical
properties of the tissue surface (see Eq. (10)). An
analytical solution for the fluence rate inside tissue
in a spherical cavity is provided as [104]:
 
3S mtr emeff ðrr0 Þ 2 emtr ðrr0 Þ
fðrÞ ¼  : ð13Þ
4p rð1 þ meff r0 Þ 3 r2
The light fluence rate depends in a complex way on
the optical properties ma and m0s and also varies on
the radius of the cavity [102]. Figure 7(a)–(c)
(dashed-dotted lines) shows the light fluence rate,
normalized to S/4pr2, vs. meff for a range of m0s be-
tween 2 and 20 cm1 for a MS point source inside a
10 cm radius sphere at 0.5 cm depth. Comparing the
multiple scattering (MS) point source (dashed-dotted
lines) to the planar source (dashed line) at the same
depth in tissue (0.5 cm), the former is 3–7 times
higher than the later, depending on the optical prop-
erties. This increased value is due entirely to the ef-
1
User’s manual of SphereOptics, “Integrating sphere Design and
Applications Technical Information.”
# 2011 by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
 Journal of

BIOPHOTONICS
784 J. L. Sandell and T. C. Zhu: Review of optical properties

fect of multiple scattering, with minor influence due Julia L. Sandell received her
to the curvature of the 10 cm sphere compared to MS in 2009 in Physics from
that of the flat semi-infinite geometry. The light flu- the University of Pennsylva-
ence rate for multiple scattering conditions is also nia, and is currently working
higher than that without multiple scattering at tissue on her Ph.D. dissertation un-
surface (Figure 7(d) for MS point source vs. Figure 6 der the advisement of Drs.
for collimated planar source). Staveren et al. [102, Timothy C. Zhu and Jarod
105, 106] found that at the cavity boundaries, diffu- C. Finlay in the Department
sion theory fails while MC simulations still work. of Radiation Oncology at
The light fluence rate inside the cavity is affected by the University of Pennsylva-
the index of refraction of the non-scattering medium nia. Her dissertation work
inside the cavity and that of tissue at the boundaries focuses on in vivo spectroscopy and dosimetry of hu-
[102, 103]. The presence of scattering medium inside man and animal tissues PDT.
the cavity causes a significant increase in the reflec-
tion factor b, which at wavelengths lower than
630 nm causes a reduced integrating sphere effect, Timothy C. Zhu received his
where the backscattered light does not increase the Ph.D. in Physics from Brown
overall fluence as greatly as at higher wavelengths University. He is currently a
[105]. Staveren et al. [106] also found that for a rela- professor at the Department
tively large b the position of the light does not of Radiation Oncology of
greatly affect the fluence rate within the cavity, the University of Pennsylva-
which is mostly due to scattered light from the nia. His current research in-
source. Marijnissen et al. [107] found b to vary terests include explicit PDT
greatly (2:5 < b < 7:1) which reveals how different dosimetry, integrated sys-
amounts of increased scattered light will be from pa- tems for interstitial and in-
tient to patient. tracavitory PDT, diffuse op-
The effect of tissue optical property heterogene- tical tomography, in-vivo
ity on the light fluence rate inside a cavity remains dosimetry, and external beam radiation transport.
to be examined. In addition, future work must ac-
count for the effect of the arbitrary shape of cavities
in clinical settings with the indices of refraction at
the cavity-tissue boundary mismatched.
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6. Conclusion
In vivo optical properties are critical quantities that
determine the fluence rates in tissues. Several spec-
troscopic techniques can be used to determine the
optical properties, but the most commonly used tech-
nique is the CW broadband diffuse reflectance,
which is both inexpensive and well tested. A table of
in vivo optical properties for human tissue, published
in the literature over the last two decades, is com-
piled for different tissue types of the human body
along with the absorption and scattering spectra of
several organs.
Acknowledgements The authors would like to thank
useful discussions with Jarod C Finlay, Ken Wang, and
Craig Grossman. One of the authors (JS) would like to
acknowledge the financial support of Fontaine Founda-
tion. This work is supported by grants from National Insti-
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