International Journal of Heat and Mass Transfer 54 (2011) 5459–5469

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International Journal of Heat and Mass Transfer

journal homepage: www.elsevier.com/locate/ijhmt

A combined transient thermal model for laser hyperthermia of tumors

with embedded gold nanoshells
Leonid A. Dombrovsky a,⇑, Victoria Timchenko b, Michael Jackson c, Guan H. Yeoh b
a
Joint Institute for High Temperatures, Krasnokazarmennaya 17A, NCHMT, Moscow 111116, Russia
b
School of Mechanical and Manufacturing Engineering, Univ. New South Wales, Sydney 2052, Australia
c
Department of Radiation Oncology, Prince of Wales Hospital, NSW, Sydney 2031, Australia

a r t i c l e i n f o a b s t r a c t

Article history: A combined thermal model for transient temperature field in a tumor and ambient tissue during laser
Received 28 June 2011 heating of embedded gold nanoparticles is developed. The approach considered is based on coupling of
Received in revised form 26 July 2011 the particular models for the absorbed radiation power and transient temperature field. A modified
Accepted 26 July 2011
two-flux approximation is used for the radiative transfer in a scattering tissue containing absorbing
Available online 9 September 2011
gold nanoshells. The spectral properties of silica-core gold nanoshells are calculated using the Mie the-
ory. The transient energy equation for composite human tissue takes into account the metabolic heat
Keywords:
generation and heat conduction, the heat transfer with blood perfusion through capillary tubes, the
Cancer
Hyperthermia
continuous or periodic laser heating, and also heat transfer of a human body with ambient medium.
Laser heating A simplified example problem for a superficial human cancer is solved numerically to illustrate the rel-
Gold nanoshells ative role of the problem parameters on the transient temperature field in a human body during hyper-
Absorption and scattering thermia treatment.
Transient thermal model Ó 2011 Elsevier Ltd. All rights reserved.

1. Introduction
The use of laser light directly or via minimally invasive fiber
optics for induced thermal treatment (hyperthermia) of tumors is
one of the present-day tools to fight cancer [1–4]. The normal
human tissues are highly scattering but weakly absorbing
(semi-transparent) media in the wavelength range form about
0.6 to 1.4 lm providing a ‘‘therapeutic window’’. The absorption
of laser light leading to a targeted heating of the tumor cells can
be strongly increased by embedding silver or gold nanoparticles
in the tumor. These nano-sized noble metal particles are character-
ized by strong resonance absorption and relatively weak scattering
in the therapeutic window. Particularly, one can chose geometrical
parameters of silica-core gold nanoshells to make these particles
very good absorbers for the light of a widely used helium–neon la-
ser with the radiation wavelength 0.6328 lm.
Nanoscale thermal therapy of targeted cancer cells is a promis-
ing new weapon in the battle against cancer. A combination of
hyperthermia with radiotherapy and chemotherapy is also consid-
ered by many researchers. Therefore, many studies have been pub-
lished on different aspects of the complicated and multi-faceted
problem of photothermal therapy. Theoretical studies were fo-
cused on unusual resonance optical properties of various gold
⇑ Corresponding author. Tel.: +7 499 250 3264; fax: +7 495 362 5590.
E-mail address: ldombr@yandex.ru (L.A. Dombrovsky).
nanoparticles in the visible and near infrared spectral ranges, mod-
eling of propagation of laser radiation in various human tissues
with embedded nanoparticles, and developing of specific heat
transfer models taking into account heat conduction, blood perfu-
sion, metabolic heat generation, and radiative power absorbed in
the processed tissues. A reader is directed to recent key publica-
tions [5–10] to learn about the state-of-the-art in this research
field. Laser irradiation in combination with hollow gold nanoparti-
cles has been recently used in the treatment of melanoma in mice
[11].
It is known that no measurable effects are observed while heat-
ing part of the human body up to about 42 °C. The first mechanism
by which biological tissue is thermally affected can be attributed to
some changes of molecules. These effects, accompanied by bond
destruction and membrane alterations, are summarized in the
term hyperthermia ranging from about 42 to 50 °C. If such a hyper-
thermia lasts for several minutes, a significant percentage of the
tissue will undergo necrosis [12]. Strictly speaking, the thermal
problem of hyperthermia should be considered by taking into ac-
count the kinetics of the cell destruction processes as described
by the Arrhenius-type equation. In the present paper, we consider
only the initial period of the so-called soft thermal treatment when
the thermal damage is not so important either for the tissue
physical properties or the temperature field in the body. Of course,
a complete analysis of thermal processes during long-term
treatment should include the effect of tissue damage but this is
beyond the scope of this paper.

0017-9310/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.ijheatmasstransfer.2011.07.045
5460 L.A. Dombrovsky et al. / International Journal of Heat and Mass Transfer 54 (2011) 5459–5469

Nomenclature

a particle radius e volume fraction of blood

c specific heat capacity h angle measured from the normal
C coefficient introduced by Eq. (16) j index of absorption
d thickness of tissue layer k wavelength
D radiation diffusion coefficient l cosine of an angle
E function introduced by Eq. (16) l asymmetry factor of scattering
fv volume fraction of particles n coefficient introduced by Eq. (7)
F, G functions introduced by Eq. (17) q density
g unknown function in Eq. (23) r scattering coefficient
h heat transfer coefficient s optical thickness
I radiation intensity u, w functions introduced by Eq. (22)
J diffuse radiation intensity U scattering phase function
k thermal conductivity x scattering albedo
m complex index of refraction ~
X unit vector of direction
M coefficient introduced by Eq. (7)
n index of refraction Subscripts and superscripts
p porosity a absorption
q heat flux b blood
Q efficiency factor c cooling
~
r spatial coordinate cr critical
R reflection coefficient e external
t time f Fresnel’s
T temperature g gold
u velocity h heating
v perfusion rate i initial
W power m metabolic
x diffraction parameter n normal
z coordinate across the layer r radiative
s scattering
Greek symbols si silica
a absorption coefficient t tissue
b extinction coefficient tr transport
c coefficient introduced by Eq. (25) w water
d relative radius of the particle core z in z-direction
D characteristic size of tumor k spectral

In the present paper, a combined transient heat transfer model
for laser thermal treatment of tumors with embedded gold nano-
shells is developed. At every stage of the problem solving, the sim-
plest approach was used as it enabled us to take into account
various physical processes without considerable mathematical dif-
ficulties. In the section concerning the radiative properties of single
silica-core gold nanoshells, a possible use of simple relations of the
Rayleigh approximation instead of the general Mie theory was
examined. In radiation heat transfer modeling, a modified two-flux
approximation was employed instead of the complete radiative
transfer equation (RTE). Mathematically, it means that we
considered a boundary-value problem for the second-order
ordinary differential equation which is much simpler than the
integro-differential RTE formulated for the radiation intensity
depending on both spatial and angular variables. We also
simplified the combined heat transfer problem by using a
one-dimensional model of the process. Specific conditions of the
thermal problem under consideration make it possible to employ
a simplified equilibrium model for the temperature field. This
model leads to a transient single energy equation instead of two
coupled equations for tissue and arterial blood. As was mentioned
above, we do not consider these assumptions valid for long-term
hyperthermia.
The papers by Tjahjono and Bayazitoglu [13] and Vera and
Bayazitoglu [14,15] can be considered as prototype studies of our
work. The objective of the present paper was to take into account
the effect of the human tissue index of refraction on both radiative
properties of gold nanoshells and radiative transfer in a tissue layer
and also to suggest a more accurate formulation for the transient
combined heat transfer problem taking into account blood perfu-
sion and metabolic heat generation.
The complete calculations for a model problem with realistic
parameters of human tissues are also given in the paper. It should
be emphasized that presented example problem is still far from
current medical practice and should be considered only as one of
the first steps towards the computational modeling of complex
processes in human body during laser thermal treatment of tumors
with embedded gold nanoparticles.
2. Spectral optical properties of a human tissue with embedded
gold nanoparticles
It is known that spectral absorption and scattering coefficients
of a composite medium which can be treated as a matrix (host
medium) containing a not too high volume fraction, fv, of small
spherical particles of the same radius a can be calculated using
the following simple relations [16]:
Qa Q tr
ak ¼ at;k þ 0:75f v rtrk ¼ rtrt;k þ 0:75f v s
ð1Þ
a a
where ak is the absorption coefficient and rtr k ¼ ð1  lk Þrk is the

transport scattering coefficient (rk is the ordinary scattering coeffi-
 k is the asymmetry factor of scattering), Qa and Q tr
cient, l s are the
 L.A. Dombrovsky et al. / International Journal of Heat and Mass Transfer 54 (2011) 5459–5469
dimensionless efficiency factor of absorption and transport effi-
ciency factor of scattering for single particles. The first terms in rela-
tions (1) correspond to the host medium whereas the second terms
are the contributions due to embedded particles. We introduced the
so-called ‘‘transport’’ scattering properties because they are the
most important parameters which determine the radiative transfer
in scattering media [16]. The latter will be clarified in one of the
subsequent sections of the paper. Note that the extinction coeffi-
cients bk = ak + rk and btr
k ¼ ak þ rk are often used in the optics of
tr
scattering media. The relations (1) allow a separate consideration
of the optical properties of human tissues and single gold nanopar-
ticles embedded in the tissue.
One should recall that human tissues are also complex disperse
systems (even without embedded gold nanoparticles). Fortunately,
in the most important spectral range of semi-transparency, the
most of soft tissues are close to optically soft media with optical
constants satisfying the following conditions:
jt  1 jnt  1j  1
where jt and nt are the spectral indices of absorption and refraction,
respectively. In this case, the absorption coefficient at,k and trans-
port scattering coefficient rtrt;k are practically independent of each
other. The absorption coefficient of a tissue with hypothetical large
pores is determined by the local value of spectral absorption index
of the substance and totally insensitive to the tissue morphology:
4pjt
at;k ¼ ð1  pÞ
k
where p is the tissue porosity (void fraction). In further analysis, we
consider the case of p = 0. On the contrary, the value of rtrt;k is prac-
tically independent of absorption and mainly determined by the tis-
sue morphology and the resulting spatial variation of the refraction
index [17].
It is known that both scattering and absorption properties of
gold nanoparticles depend on optical constants of the ambient
medium. In the region of the tissue semi-transparency, where
jt  nt, the effect of absorption index is negligible and it is suffi-
cient to know the local tissue index of refraction [16].
2.1. Optical properties of human tissues
It is well known that soft human tissues are semi-transparent
for long-wave (red) visible light and for adjacent (in spectrum)
near-infrared radiation. Of course, various tissues have specific
optical properties but the most wide therapeutic window consid-
ered in literature is a wavelength range from 0.6 to 1.4 lm [18].
According to [7], ordinary biotissues are almost transparent in
the near-infrared range from k = 0.75 lm to 1.1 lm where the
spectral absorption coefficient is especially small: at,k < 0.5 cm1.
One can find a lot of particular (but not quite complete) data for
optical properties of tissues of various human and animal organs
in the literature [18–21]. In addition to the absorption coefficient,
the data for the scattering coefficient, asymmetry factor of scatter-
ing, and index of refraction are usually given.
A significant portion of tissues contains water which refractive
index (nw = 1.33) represents the minimum value of the refractive
index for fluids and soft-tissue constituents. Among the other
soft-tissue components, melanin particles, found mostly in the epi-
dermal layer of skin, are at the high end of the refractive index
scale, with reported values above 1.6 [18].
The radiation scattering in tissues occurs where there is a spa-
tial variation of the refractive index, either continuous or abrupt
(e.g., due to localized particles). In cellular media, the important
scatterers are the subcellular organelles. The size range exhibited
by these organelles includes the wavelength of the therapeutic
window, as their dimensions run from less than 100 nm to 6 lm.
5461
As scatterers, most of these structures fall in the so-called Mie re-
gime, exhibiting highly anisotropic forward-directed scattering
patterns [18]. Note that disk-shaped red cells (erythrocites) are
the strongest scatterers in blood because the erythrocyte disk is
about 2 lm thick with a diameter of 7 to 9 lm.
The methods developed for identification of the main spectral
characteristics of absorption and scattering of diverse disperse
media are usually based on the measurements of directional-
hemispherical reflectance and transmittance of collimated radia-
tion for small plane samples of the material. One can find the de-
tails of the experimental procedure and inverse problem solution
in recent book by Dombrovsky and Baillis [16] and review papers
by Baillis and Sacadura [22], Sacadura [23], and Dombrovsky
et al. [24]. Similar experimental methods are also employed to
determine the optical properties of human tissues in the visible
and near infrared spectral ranges. Of course, there is a definite spe-
cific of in vivo optical measurements described in some details by
Bargo et al. [25].
ð2Þ
In contrast to healthy tissues, current data for optical properties
of tumor tissues are far from complete and the experimental stud-
ies of these properties are continuing. In particular, the data for
absorption and extinction coefficients of mammary fibroadenoma
tissue at the wavelength k = 0.63 lm have been recently reported
by Chaikovskaya et al. [26]. The obtained values of the absorption
coefficient were found to be in the range from at,k = 0.96 to
1.45 cm1, as well as the extinction coefficient is much greater:
ð3Þ from bt,k = 133.7 to 191 cm1. The values of asymmetry factor of
scattering appeared to be in the range from l  t;k ¼ 0:92 to 0:96. It
was noted in [26] that the values obtained are of the same order
of magnitude as the values of at,k = 0.52 cm1 and bt,k = 144 cm1
at k = 0.7 lm from the book by Tuchin [21]. This example indicates
that optical properties of tissues are very specific, patient depen-
dent, and there is a considerable uncertainty in the experimental
results even for the same type of tumor. This leads to a limited
accuracy of the radiative transfer predictions, which are important
for any computational modeling of photothermal therapy process.
To our mind, this drawback can be and should be partially compen-
sated by in situ measurements of all the important parameters
during laser targeted thermal treatment of cancers.
2.2. Optical properties of gold nanoshells
Following [13–15], we considered only one type of gold nano-
particles which can be used in laser based hyperthermia. These
two-layer spherical particles consist of a silica core and relatively
thin gold mantle. It is clear that one needs the data for optical con-
stants of both silica and gold to calculate optical properties of such
silica-core gold nanoshells.
The optical constants of gold in the short wave part of the spec-
tral range considered in the present study are presented in Fig. 1.
One can see that there is a discrepancy between spectrally com-
plete early data for absorption index reported by Schulz [27] and
the tabulated data recommended by Lynch and Hunter [28] with
no data in the important range from k = 0.5636 to 0.6526 lm. At
the same time, there is a good agreement between data of
[29,28] for spectral index of refraction. In further calculations, we
will use the interpolated data from papers [27,29] but the effect
of this choice on the computational results appeared to be very
small. The above illustrated specific optical properties of gold are
explained by a high electric conductivity of this substance due to
presence of numerous free electrons. As a result, the index of
absorption is almost directly proportional to the wavelength and
the index of refraction is less than one.
The index of refraction of fused quartz (pure silica, SiO2) at
room temperature in the spectral range of interest is well
5462 L.A. Dombrovsky et al. / International Journal of Heat and Mass Transfer 54 (2011) 5459–5469

6 1 þ d3 M m2g  n2si
n¼ 3
M¼ ð7Þ
1  2d M 2m2g þ n2si
5
Note that the Rayleigh approximation is a particular case of the rig-
4 orous Mie solution and the Rayleigh formulae can be easily derived
κg from the first term of the Mie series. This term corresponds to the
ng, κg

3 simplest partial wave. It is the so-called electric dipole scattering.

To determine the absorption and scattering properties of typical
single nanoshells, the Mie theory calculations were performed for
2 1
nanoshells with fixed external radius a = 20 nm and variable rela-
2
tive radius d of the silica core. The computational results in the
1 wavelength range of 0.5 < k < 0.8 lm, presented in Fig. 2 are given
ng for two values of the ambient tissue refractive index of nt = 1.4 and
0 1.45. One can see a similar resonance behavior of both absorption
0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 and transport scattering efficiency factors with a great effect of the
λ, μm gold mantle thickness. The same qualitative result has been ob-
tained by Averitt et al. [34] for gold-coated Au2S nanoshells. They
Fig. 1. Optical constants of gold at room temperature: 1 – from [25,27], 2 – from
found that a variation of d from 0.6 to 0.9 yields a plasmon reso-
[26].
nance tunable from 0.6 lm to greater than 1 lm. This unusual
physical behavior of gold nanoshell optical properties has been
described by the three-term dispersion relation suggested by also considered by Loo et al. [35] and Cleveland et al [36]. It is
Malitson [30]: interesting that the results are sensitive to a small variation of
the ambient tissue refractive index. Note that the latter gives a pos-
0:6962k2 0:4079k2 0:8975k2 sibility of sensitive optically based chemical detectors [37–41].
n2si  1 ¼ þ þ ð4Þ
k2  0:004679 k2  0:01351 k2  97:93 Let us compare the exact results obtained using the Mie theory
where k is expressed in microns. In Eq. (4), approximate values of with the Rayleigh approximation which is expected to be applica-
coefficients are given. The index of refraction calculated by use of ble for so small particles. A comparison presented in Fig. 3 shows
Eq. (4) varies from 1.458 to 1.446 with the wavelength from
k = 0.6 to 1.4 lm. Of course, we use the constant value of
nsi = 1.45 for silica core of gold nanoshells in our calculations. The 10 a 0.8
detailed data for silica index of absorption can be found in review
paper by Kitamura et al. [31]. But the values of jsi in the therapeutic
spectral window are so small that one can assume jsi  0. 8 0.7
nt=1.4
The ambient tissue is also a weakly absorbing substance and
0.6 1.45
one can assume jt  0 at least in calculations of the optical proper-
6
ties of gold nanoshells. The classical Mie solution for the absorp-
Qa

tion and scattering of radiation by a spherical particle relates to δ =0

the case when the particle is surrounded by vacuum. According 4
to the Mie theory, the efficiency factors of absorption and scatter-
ing of core-mantled particles depend on the diffraction parameter
2
x = 2pa/k, relative core radius and the complex indices of refraction
of the particle materials msi  nsi and mg = ng  ijg. The formulae of
the Mie theory are also valid for particles immersed in a refracting 0
medium with index of refraction nt. In so doing, the quantities 0.50 0.55 0.60 0.65 0.70 0.75 0.80
~ si ¼ nsi =nt ; m
n ~ g ¼ mg =nt and ~
x ¼ nt x should be substituted for nsi, λ, μm
mg and x as independent variables in calculating the Mie coeffi- 1.6
cients [32]. The computational results presented below were ob- b
tained using the Mie theory code published in the Appendix of 1.4 0.8
the book [33]. All the relations can be found also in monograph
[16]. 1.2
0.7 nt=1.4
One can expect that optical properties of gold nanoshells can be
1.0 1.45
calculated much simpler because of very small size of these parti-
cles as compared with the wavelength. This can be done using the 0.8 0.6
tr
Qs

Rayleigh theory which is applicable when the following conditions

are satisfied: 0.6
δ =0
~x  1 nsi xd  1 jmg jx  1 ð5Þ 0.4

The Rayleigh relations for absorption and scattering properties of 0.2

gold nanoshells are [16]:
!  2 0.0
nm ~ 2g tr 8 4  m~ 2g  n  0.50 0.55 0.60 0.65 0.70 0.75 0.80
Q a ¼ 4~xIm ~
Qs  Qs ¼ x  2  ð6Þ λ, μm
~ 2g þ 2n
m 3 m ~ g þ 2n
Fig. 2. Efficiency factor of absorption (a) and transport efficiency factor of scattering
where
(b) of gold nanoshells with external radius a = 20 nm and various values of a relative
radius of silica core at two values of the ambient tissue refractive index.
 L.A. Dombrovsky et al. / International Journal of Heat and Mass Transfer 54 (2011) 5459–5469 5463

d ¼ 0:7316 Q a ¼ 7:978 Q tr
s ¼ 1:053 when nt ¼ 1:4 ð8aÞ
12 a
0.8 d ¼ 0:7196 Q a ¼ 8:181 Q tr
s ¼ 1:201 when nt ¼ 1:45 ð8bÞ
10
The above optimal choice of a relative radius of the silica core is not
8 δ =0.7 1 realistic because we do not know the exact value of the tumor tissue
2 refractive index. Therefore, it seems reasonable to assume the same
6 value of d in model calculations at various values of nt. In the pres-
Qa

ent paper, the following theoretical properties of a silica-core gold

4 nanoshell at wavelength k = 0.6328 lm are used:

ð7:716; 1:044Þ; nt ¼ 1:4
2 d ¼ 0:725 ðQ a ; Q tr
s Þ ¼ ð9Þ
ð7:828; 1:144Þ; nt ¼ 1:45
0 It can be easily shown that the transport scattering coefficient of
0.50 0.55 0.60 0.65 0.70 0.75 0.80 gold nanoshells at realistic volume fraction fv < 105 is less than
λ, μm that of tumor tissues. At the same time, the absorption coefficient
2.0 of tumor tissues is small as compared with the absorption coeffi-
cient of gold nanoshells at fv > 107. The latter determines the most
1.8 b
interesting range of 106 6 fv 6 105 considered in the present
0.8
1.6 paper.
1.4

1.2 δ =0.7 1 3. Radiative transfer modeling

1.0
2
In our study, we employed a continuum approach to model the
tr
Qs

0.8 radiative transfer in a complex medium containing scattering (and

0.6
weakly absorbing) tissue and absorbing (and weakly scattering)
nanoparticles. The so-called radiative transfer equation (RTE) is
0.4 considered in the traditional continuum theory. In the case of a
0.2 negligible emission of the radiation by a scattering and absorbing
medium, the RTE can be written as follows [16,42,43]:
0.0
0.50 0.55 0.60 0.65 0.70 0.75 0.80 Z
~rIk ð~ ~Þ þ b Ik ð~ ~Þ ¼ rk ~0 ÞUk ðX ~ÞdX
~0 X ~0
λ, μm X r; X k r; X Ik ð~
r; X ð10Þ
4p ð4pÞ
0.25
The physical meaning of Eq. (10) is evident: variation of the spectral
c radiation intensity in direction X ~ takes place due to extinction by
0.20 absorption and by scattering in other directions, as well as due to
scattering from other directions (the integral term). The absorption
coefficient, ak, the scattering coefficient, rk, and scattering phase
0.15 function, Uk, depend on the coordinate ~ r. For simplicity, Eq. (10)
δ =0.7
is written for the case of an isotropic medium when the coefficients
ωtr

of RTE do not depend on direction. One can also consider more gen-
0.10 0.8 eral case of anisotropic medium but this is not so important for
optically thick highly scattering tissues [16].
1 Generally speaking, one can consider the most general form of
0.05
2 the RTE, the so-called vector RTE (VRTE), which fully accounts for
the polarization nature of light and is applicable to scattering med-
0.00 ia composed of arbitrary shaped and arbitrary oriented particles.
0.50 0.55 0.60 0.65 0.70 0.75 0.80 The VRTE is formulated for the Stokes column vector (instead of
λ, μm the radiation intensity), and the scattering matrix is used instead
of the scattering phase function in the VRTE integral term [44].
Fig. 3. Efficiency factor of absorption (a), transport efficiency factor of scattering
The polarization effects are really important in remote sensing
(b), and transport albedo (c) of gold nanoshells with external radius a = 20 nm and
various values of a relative radius of silica core at fixed value of the ambient tissue and in specific problems of microwave radiation. Fortunately, one
refractive index nt = 1.45: 1 – Mie theory, 2 – Rayleigh approximation. can ignore polarization of the infrared radiation in most of applied
problems for dispersed materials. Moreover, the details of scatter-
that simple relations (6) and (7) based on the Rayleigh theory give ing phase function are not important when hemispherical charac-
qualitatively true spectral dependencies and an excellent result for teristics of the radiation field are considered. In this case, it appears
the nanoshell transport albedo xtr ¼ Q tr tr
s =ðQ a þ Q s Þ. The latter can to be sufficient to know the so-called asymmetry factor of scatter-
be used in practical estimates. At the same time, the error in values ing, which is independent of polarization [16].
of the efficiency factors is considerable. It goes without saying that A complete and accurate solution to the RTE in scattering media
this error decreases very fast with decreasing the nanoshell size. is a very complicated task because of the integral term in the right-
In the present paper, we consider the irradiation of human tis- hand side of the RTE. One can find a lot of studies in the literature
sue by a helium–neon laser with the wavelength k = 0.6328 lm. If on specific numerical methods developed to obtain more and more
we consider gold-coated silica nanoshells with radius a = 20 nm accurate spatial and angular characteristics of the radiation inten-
which give the maximum absorption at this wavelength, the Mie sity field. Several modifications of the discrete ordinates method
theory yields the following values of d and efficiency factors: (DOM) and statistical Monte Carlo (MC) methods are the most
5464 L.A. Dombrovsky et al. / International Journal of Heat and Mass Transfer 54 (2011) 5459–5469

Z 1
popular tools employed by many authors (see monographs @I rtr
[16,42,43]). As to the applied problem under consideration, one
l þ btr I ¼ Iðz; lÞdl l ¼ cos h 0 < z < d ð13Þ
@z 2 1
can refer to recent papers by Fasano et al. [45] and Banerjee and
Sharma [46] where the MC method is used in biomedical The boundary conditions at two surfaces of the layer are:
applications.
To avoid additional mathematical complexity, we prefer to use Ið0; lÞ ¼ Rf Ið0; lÞ þ ð1  Rf ÞIe dð1  lÞ
a simplified approach to the problem and focus on analysis of the Iðd; lÞ ¼ Rt Iðd; lÞ l>0 ð14Þ
interaction of physical processes. The specific problem statement
makes possible the use the well-known transport approximation where Ie is the incident spectral radiation intensity, Rf is the Fres-
for the scattering phase function [16,47]. According to this approx- nel’s reflection coefficient [51]:
imation, the scattering phase function is replaced by a sum of the
isotropic component and the term describing the peak of forward Rf ¼ ðRjj þ R? Þ=2 ð15aÞ
scattering: ( pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi)2
Uk ðls Þ ¼ ð1  l
 k Þ þ 2l
 k dð1  ls Þ ð11Þ l  nt 1  n2t ð1  l2 Þ
Rjj ¼ pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
l þ nt 1  n2t ð1  l2 Þ
With the use of transport approximation, the RTE can be written in ( pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi)2
the same way as that for isotropic scattering, i.e. with Uk  1: nt l  1  n2t ð1  l2 Þ
R? ¼ pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi when l 6 lcr ð15bÞ
Z nt l þ 1  n2t ð1  l2 Þ
~rIð~ ~Þ þ b Ið~ ~ rtr ~0 ÞdX
~0
X r; X tr r; XÞ ¼ Ið~
r; X ð12Þ
4p ð4pÞ qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
Rjj ¼ R? ¼ 1 when l 6 lcr ¼ 1  1=n2t ð15cÞ
Hereafter, the subscript k is omitted for brevity. The transport
approximation is widely used in radiative transfer calculations dur-
We assume here that the tissue index of absorption is relatively
ing many years. It was confirmed that hemispherical characteristics
small: jt  nt. The value of Rf = 1 for l 6 lcr corresponds to the to-
of radiation field in scattering materials are well described using
tal internal reflection. The reflection coefficient Rt from the scatter-
this approximation [16]. The latter makes the quantity rtr to be
ing tissue at the other boundary of the computational region will
the most important scattering property of the medium. It should
be determined below. Note that assumption of Rt = 0 used in pa-
be noted that the transport approximation is also applicable to
pers [13–15] is not correct because of high albedo of the human
rather complex multi-dimensional radiative transfer problems [48].
tissue. The reflection of radiation from a human tissue at the sha-
Let us consider the simplest model problem to study the effect
dow side of the layer containing absorbing particles may lead to a
of the main physical parameters on volumetric absorption of the
considerable increase of absorption across the absorbing layer
incident collimated radiation by a scattering medium. We assume
when optical thickness of this layer is small.
that a plane-parallel layer of the medium is illuminated along the
Following the usual technique consider the radiation intensity I
normal and the incident beam cross dimensions are much larger
as a sum of the diffuse component J and the term, which corre-
than the medium layer thickness. The latter enables us to ignore
sponds to the transmitted and reflected directional external
the radiation energy transfer along the layer and consider a simple
radiation:
one-dimensional radiative transfer problem in the incident beam
direction. 1  Rf ;n
The schematic of the particular example problem in which the I¼Jþ ½Edð1  lÞ þ ðC tr =EÞdð1 þ lÞIe ð16Þ
1  Rf ;n C tr
layer is illuminated from one side by a collimated monochromatic
radiation is presented in Fig. 4. The geometrical parameters of this where Rf,n = Rf(1) and Rt,n = Rt(1) are the normal reflection coeffi-
simplified picture were taken from papers by Çetingül and Herman cients and
[49,50]. The properties of the tissues will be specified in the next Z z
section of the paper. The shadow surface of the layer is character- E ¼ expðstr Þ str ¼ btr dz C tr ¼ Rt;n expð2s0tr Þ
ized by a surface albedo. In other words, we should take into ac- 0
Z d
count the radiation scattered from the medium beyond the
computational region. After integration over an azimuth angle, s0tr ¼ btr dz ð17Þ
0
the RTE can be written in the transport approximation as follows
[16]: The mathematical problem statement for the diffuse compo-
nent of radiation intensity is as follows:
Z 1
@J rtr 1  Rf ;n
without embedded gold nanoshells

l þ btr J ¼ ðG þ FÞ G ¼ Jdl F ¼ ðE þ C tr =EÞIe

2 1  Rf ;n C tr
thick layer of a healthy tissue

@z 1

incident ð18Þ
radiation
Jð0; lÞ ¼ Rf ðlÞJð0; lÞ Jðd; lÞ ¼ Rt ðlÞJðd; lÞ l>0 ð19Þ

1 3 4 5 The spectral radiation power absorbed in the medium, W, is ex-

pressed as

Z 1
dI
0 W ¼ ldl ¼ aðG þ FÞ ð20Þ
d z 1 dz
In the range of semi-transparency, the index of absorption of
2, tumor 1, 3, 4, 5 - healthy tissues human tissue is small as compared with the index of refraction.
Therefore, one can use approximate formula for the Fresnel normal
Fig. 4. Schematic of a one-dimensional model problem with five layers of tissues. reflectance:
 L.A. Dombrovsky et al. / International Journal of Heat and Mass Transfer 54 (2011) 5459–5469 5465

 2
nt  1 not difficult to obtain a numerical solution for the simplified spec-
Rf ;n ¼ ð21Þ tral radiative transfer problem. The computational results for the
nt þ 1
model problem will be presented and discussed below. In the pres-
The normal reflectance at the boundary inside the tissue (at z = d) ent section, we give only some general comments on the known
can be simply obtained from analytical solution derived by features of the radiation absorption profiles. It seems obvious that
Dombrovsky et al. [52]: external radiation is absorbed first of all in a surface layer of irra-
xe diated medium and the absorbed specific power decreases with
Rt;n ¼  pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffitr pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi ð22Þ the distance from the illuminated surface. This is really true in
1 þ 1  xetr 1 þ 2 1  xetr
the case of a purely absorbing medium when there is no scattering.
where xetr ¼ retr =betr is the transport albedo of a healthy tissue out- In the general case of an absorbing and scattering medium, the
side the computational region (see Fig. 1). monotonic absorption profiles are observed only in the case of dif-
The above formulated problem for the diffuse component of the fuse irradiation. It is not the case for the interaction of collimated
radiation intensity is still very complex. To simplify this problem incident radiation with a semi-transparent highly scattering med-
one can use simple analytical representations of the angular ium. One can observe a local maximum of volumetric absorption at
dependence of the radiation intensity. It is known that the latter some distance from the illuminated surface.
leads to the so-called differential approximations for radiative
transfer [16]. As for the choice of a differential approximation,
4. Transient energy equation for combined heat transfer in
one can use the first-order approximation of the spherical harmon-
human tissues
ics method (P1) or the two-flux approximation, which is equivalent
to the zero-order approximation of the double spherical harmonics
The energy transport in a biological system is usually expressed
(DP0) [16]. The P1 approximation used by Tjahjono and Bayazitoglu
by the so-called bioheat equation. The bioheat equation developed
[13] and Vera and Bayazitoglu [14,15] is a more general method
by Pennes [54] is one of the earliest models for energy transport in
and it can be used in multi-dimensional problems. At the same
tissues. Pennes assumed that the arterial blood temperature, Tb, is
time, the modified two-flux approximation suggested by
uniform throughout the tissue while the vein blood temperature is
Dombrovsky et al. [53] is preferable for the particular model con-
equal to the local tissue temperature T. The resulting transient en-
sidered in the present paper because of discontinuous angular
ergy equation is as follows:
behavior of the radiation intensity and the effect of total internal
reflection at the interfaces [16]. @T
qc ¼ rðkrTÞ þ qb cb v b ðT b  TÞ þ W m ð29Þ
In the modified two-flux approximation, the following repre- @t
sentation for the angular dependence of radiation intensity is
where the second term on the right-hand side is responsible for the
considered [16,53]:
8  heat transfer due to arterial blood perfusion of rate vb, and the last
< u ðzÞ; 1 6 l < lcr
> term Wm is the metabolic heat generation within the tissue. A more
Jðz; lÞ ¼ wðzÞ; lcr < l < lcr ð23Þ detailed model for heat transfer in human tissues should be based
>
: þ on two coupled energy equations for the tissue and artery blood.
u ðzÞ; lcr < l 6 1
Of course, the spatial and time variation of arterial blood tempera-
Note that the case lcr = 0 corresponds to the ordinary two-flux ture is taken into account in such a model. The details of advanced
model. The intermediate angle interval lcr < l < lcr gives no con- heat transfer models derived on the basis of a general heat transfer
tribution to the radiation flux and the words ‘‘two-flux’’ are applica- theory in porous media can be found in [5,8].
ble to the modified approximation too. Integrating Eq. (18) In the hyperthermia, the temperature variation due to thermal
separately over the intervals 1 < l < lcr, lcr < l < lcr, and treatment is usually much greater than the difference between lo-
lcr < l < 1, after simple transformations, one can obtain the follow- cal temperatures of the tissue and blood. Therefore, this difference
ing boundary-value problem for the function g = u + u+: can be neglected, at least in the approximate thermal model, and
  with assumption of the local thermal equilibrium the energy equa-
d dg a rtr tion derived from the coupled equations for the tissue and blood
 D þ g¼ F ð24Þ
dz dz 1  xtr lcr 1  xtr lcr [5] can be written as follows:
dg cf dg c
z ¼ 0; D ¼ ð1 þ lcr Þg z ¼ d; D ¼  t ð1 þ lcr Þg ð25Þ @T
dz 2 dz 2 qc ¼ rðkrTÞ þ eqb cb~
ub rT þ ð1  eÞW m þ W ð30Þ
@t
where
where e is the volume fraction of blood. We added here the term W
ð1 þ lcr Þ2 1  Rf ;n 1  Rt;n to account for heat generation due to absorption of laser radiation
D¼ cf ¼ ct ¼ ð26Þ
4btr 1 þ Rf ;n 1 þ Rt;n by gold nanoshells. In the case of a one-dimensional problem (see
Fig. 4), the mathematical formulation is as follows:
The absorbed radiation power can be calculated using Eq. (20) and
 
the following relation between functions G and g: @T @ @T @T
qc ¼ k þ eqb cb ub;z þ ð1  eÞW m þ W ð31Þ
ð1  lcr Þg þ xtr lcr F @t @z @z @z
G¼ ð27Þ
1  xtr lcr t ¼ 0; T ¼ T i ðzÞ ð32Þ
@T
As a result, we obtain the following relation: z ¼ 0; T ¼ T w ðtÞ z ¼ d; k ¼ h2 ðT e;2  TÞ ð33Þ
@z
ð1  lcr Þg þ F
W ¼a ð28Þ The boundary condition at z = 0 corresponds to the case of water
1  xtr lc
cooling the body surface. The temperature Tw(t) is equal to the
In the case of uniform optical properties of a medium in the measured water temperature in the cooling system running during
computational region, the boundary-value problem (24), (25) can the thermal treatment. This temperature can be regulated manually
be solved analytically. But the realistic problems are characterized according to preliminary estimates and in situ diagnostics of the pa-
by different properties of tumor and healthy tissue and nonuni- tient. The boundary condition at z = d describes approximately the
form distribution of absorbing gold nanoshells. Fortunately, it is heat transfer from the internal part of the body, which has a con-
5466 L.A. Dombrovsky et al. / International Journal of Heat and Mass Transfer 54 (2011) 5459–5469

stant temperature Te,2. The initial steady-state temperature profile
Ti(z) in Eq. (32) is a solution to the following boundary-value
problem:
 
d dT i dT i
k þ eqb cb ub;z þ ð1  eÞW m ¼ 0
dz dz dz
dT i @T i
z ¼ 0; k ¼ h1 ðT e  T i Þ z ¼ d; k ¼ h2 ðT e;2  T i Þ
dz @z
In the problem statement (31)–(33), we ignore possible effect of
increase in thermal conductivity of the tumor tissue due to the
presence of nanoparticles. As was noted in Section 1, we do not
consider also kinetics of the tissue cell destruction, which is impor-
tant in the case of a long-time hyperthermia.
It is important that solution to the heat transfer problem yields
not only the transient temperature field but also the heat flux to
the cooling water
 are plotted for two values of the nanoshells volume fraction. As cal-
@T 
qw ¼ k t>0
@z z¼0
The value of the local heat flux can be obtained experimentally from
the measurements of water flow rate and temperature. In the case
of a more realistic two-dimensional problem statement, one can use
these measurements to validate the computational model and iden-
tify in situ the main parameters of the transient temperature field in
the tumor region.
5. Analysis of computational results for the model problem
The main physical parameters of the model problem for a tumor
close to the human body surface (see Fig. 3) are specified in Table 1.
The geometrical parameters, tissue density, specific heat capacity,
thermal conductivity, and the metabolic heat generation rates
were taken from papers by Çetingül and Herman [49,50]. The val-
ues of absorption and transport scattering coefficients were par-
tially taken from paper by Vera and Bayazitoglu [14] and
completed using some data reported in [18–20]. The optical prop-
erties of the layers 2, 3, and 4 should be considered as estimates
only. But the latter is not so important for the profile of the ab-
sorbed radiation power.
An estimate of the effective perfusion velocities in the normal
direction for every tissue layer was obtained from the perfusion
rate data of [49,50] by using the following relation:
eub;z ¼ ej~
uj=2 ¼ mb;j dj =2
where dj is the thickness of the jth layer. One should recall that
there is a significant uncertainty in the local blood perfusion [55],
which may increase during thermal treatment. Note that these per-
fusion rate data do not significantly alter the predicted temperature
profiles. The following values of blood density and specific heat
capacity were used in the calculations: qb = 1060 kg/m3 and
cb = 3770 J/(kg K) [49]. In the term responsible for the metabolic
heat generation in the right-hand side of Eqs. (31) and (34), a small
value of e has been neglected so that a highest estimate of the met-
abolic heat generation was obtained.
For simplicity, it was assumed that gold nanoshells were
ð34Þ embedded in the epidermis and tumor only and there was no these
nanoshells in the deeper tissues. Moreover, the case of a uniform
concentration of the gold nanoshells across the tumor was consid-
ð35Þ
ered. Note that the developed computational model allows taking
into account more realistic concentration profiles but this is not
essential for the example problem considered in this work. The
reflection coefficient at the interface between fat layer and external
(with respect to the computational region) muscle layer was
obtained assuming the muscle transport albedo equal to 0.9. The
results of radiation heat transfer calculations are presented in
Fig. 5. The profiles of a specific volumetric power of absorbed
 per unit radiation flux of the incident laser beam
radiation, W,
culations at different values of the tissue refractive index produced
ð36Þ
very close results, only the case of nt = 1.45 is presented in Fig. 5. It
should be noted that a part of laser radiation power absorbed in
R
the tissue defined as W ~ ¼ d WðzÞdz is different for the cases
0
~ increases
considered. One can see in Table 2 that the value of W
considerably with the concentration of embedded nanoshells. This
result can be explained by relatively small role of scattering at
large concentrations of highly absorbing gold nanoshells. To obtain
~ and avoid unfavorable radiative heating
the maximum value of W
of the fat layer, the value of fv = 105 was used in subsequent
calculations.
The conditions of the experimental study by Çetingül and
Herman [49] were used to determine a steady-state temperature
profile in the tissue without laser treatment. According to the mea-
surements of [49] the ambient temperature and heat transfer coef-
ficient were taken equal to Te = 22.5 °C and h1 = 10 W/(m2 K). To
calculate the heat flux from the body to the surface layer, we used
value of Te,2 = 37 °C and estimated value of h2 = 50 W/(m2 K). The
problem (34) and (35) was solved using an implicit finite-differ-
ence scheme and splitting of the right-hand side operator of Eq.
(34) (details of this procedure can be found in [56]). Calculated
steady-state temperature profiles for non-irradiated tissues are
shown in Fig. 6. As can be seen from this figure, the main temper-
ature difference takes place in the layer of low-conductivity fat and
the total effect of both local blood perfusion and metabolic heat
generation on temperature distribution is only about 0.3 °C in
the skin surface temperature.
ð37Þ
Selected typical results of a series of heat transfer calculations
obtained at constant Tw = 35 °C, nt = 1.45 and periodic laser irradi-
ation of the body surface are discussed below. We assumed that
every period of thermal treatment includes heating during the
time th with incident radiative flux q0e and the cooling period (when
there is no irradiation) of duration tc (see Fig. 7). One can see in
Fig. 8 that temperature profiles at the end of heating and cooling
time for the second period of thermal treatment are close to those

Table 1
Properties of tissues in the computational region.

Layer number 1 2 3 4 5
Tissue name Emidermis Lesion Papillary dermis Reticular dermis Fat
Layer thickness, mm 0.1 0.3 0.4 0.8 2.0
qt, kg/m3 1200 1030 1200 1200 1000
ct, J/(kg K) 3589 3582 3300 3300 3674
kt, W/(m K) 0.235 0.558 0.445 0.445 0.185
Wm, W/m3 0 3680 368.1 368.1 368.3
eub,z, 106 m/s 0 9.4 0.4 5.2 1.0
a, 1/m 180 50 20 20 10
rtr, 1/m 2360 600 200 200 400
 L.A. Dombrovsky et al. / International Journal of Heat and Mass Transfer 54 (2011) 5459–5469 5467

-1
44

1 3
1000 42
2
Papillary dermis 1 Fat layer
40
Lesion

T, C
W, m

Reticular

o
dermis Fat layer
_

100 38
4

36 2

10 34
Dermis

0.0 0.6 1.2 1.8 2.4 3.0 3.6 0.0 0.6 1.2 1.8 2.4 3.0 3.6
z, mm z, mm

Fig. 5. Profiles of the absorbed radiation power. Calculations at nt = 1.45 and two Fig. 8. Transient temperature profiles in the tissue during periodic thermal
variants of gold nanoshell volume fraction: 1 – fv = 106, 2 – fv = 105. treatment by laser radiation at th = 10 s, tc = 15 s, and q0e ¼ 20 kW=m2 (the desig-
nations 1, 2, 3, and 4 see in Fig. 7).

Table 2
Relative part of incident laser power absorbed in the tissue.
46
~
W
1
fv = 106 (%) fv = 105 (%) 44 2
nt = 1.4 44.0 85.0
nt = 1.45 45.2 85.2
42
T, C
o

34.5 40

38
34.0
Dermis Fat layer

36
33.5
Ti , C

0 10 20 30 40 50
o

t, s
33.0
Fig. 9. Time variation of temperature at the shadow site of the lesion for two
variants of a periodic laser heating with tc = 15 s: 1 – q0e ¼ 20 kW=m2 , th = 10 s, 2 –
1
32.5 q0e ¼ 30 kW=m2 , th = 5 s.
2

32.0 for the first period. Fig. 9 for the temperature at the interface of the
0.0 0.6 1.2 1.8 2.4 3.0 3.6 lesion and papillary dermis indicates that desirable variation of
z, mm
both the temperature level and duration of hyperthermia can be
Fig. 6. Calculated steady-state temperature profiles for non-irradiated tissues: 1 – obtained by a combination of the incident laser radiation flux
without blood perfusion and metabolic heat generation, 2 – complete calculation. and heating period. Note that periodic regime of heating has two
advantages as compared with the continuous heating: (1) the
ambient tissues are not overheated during the treatment and (2)
one can avoid unfavorable increase in the blood perfusion because
20 1 3
of a time delay in the natural reaction of the cardiovascular system
[57,58]. The complete time of hyperthermia can be computation-
15 ally predicted for the periodic laser irradiation. This may provide
0
qe a required thermal regime of a long-time soft thermal treatment
2
qe, kW/m

10 of some tumors.
tc
5 th
6. Conclusions
0 2 4
A combined thermal model for the transient temperature field
0 10 20 30 40 50 in a tumor and surrounding tissue during laser heating of embed-
t, s
ded gold nanoparticles in conditions of cancer hyperthermia is
Fig. 7. Typical time variation of the incident radiative flux in periodic heating. The
developed. The approach considered is based on the coupling par-
marked points 1, 2, 3, and 4 are the time moments selected for the temperature ticular models for the absorbed radiation power and transient tem-
profile analysis. perature field.
5468 L.A. Dombrovsky et al. / International Journal of Heat and Mass Transfer 54 (2011) 5459–5469
The spectral properties of nanoshells with a silica core and gold
coating are calculated using the Mie theory. It was shown that
spectral position of the plasmon resonance for these nanoparticles
is very sensitive to both the relative radius of the silica core and
refractive index of an ambient tissue. It appears that the Rayleigh
approximation yields correct values of the particle albedo and good
estimates for specific absorption and scattering properties of gold
nanoshells with radius up to 20 nm.
A modified two-flux approximation is employed for modeling
one-dimensional radiative transfer in a layer of scattering tissue
containing absorbing gold nanoshells. The boundary conditions
take into account both collimated laser radiation and reflection
of the radiation from the deeper layer of human tissue.
The simplified transient energy equation based on the hypoth-
esis of the local thermal equilibrium is considered. The problem
statement takes into account the metabolic heat generation and
heat conduction in the composite tissue, the heat transfer with
blood perfusion through capillaries, the continuous or periodic
laser heating, and specific conditions of the surface body cooling
during hyperthermia.
A simplified one-dimensional problem of a particular kind of
human cancer is solved numerically to illustrate a relative role of
the problem parameters on the transient temperature field in a
human body during hyperthermia. For the particular problem
considered, the role of both metabolic heat generation and blood
perfusion appears to be not important, and the transient tempera-
ture field in the tumor and ambient tissue can be predicted on the
basis of the traditional radiative–conductive heat transfer formula-
tion. Thermal calculations for a periodic laser irradiation showed
that a required thermal regime of a long-time soft thermal treat-
ment of some tumors can be obtained.
Acknowledgements
The first author is grateful for the partial financial support of
this work by the University of New South Wales (Sydney) and
Russian Foundation for Basic Research (Grant No. 10-08-00218a).
References
[1] D.A. Stuart, A.J. Haes, C.R. Yonzon, E.M. Hicks, R.P. Van Duyne, Biological
applications of localized surface plasmonic phenomenae, IEE Proc.-
Nanobiotechnol. 152 (1) (2005) 13–32.
[2] S. Lal, S.E. Clare, N.J. Halas, Nanoshell-enabled photothermal cancer therapy:
impending clinical impact, Accounts Chem. Res. 41 (12) (2008) 1842–1851.
[3] P. Cherukuri, S.A. Curley, Use of nanoparticles for targeted, noninvasive
thermal destruction of malignant cells, in: S.S. Grobmyer, B.B. Moudgil (Eds.),
Chapter 24 in Cancer Nanotechnology, Springer, 2010, pp. 359–373.
[4] K. Cheng, S. Sun, Recent advances in syntheses and therapeutic applications of
multifunctional porous hollow nanoparticles, Nano Today 5 (3) (2010) 183–
196.
[5] A.-R.A. Khaled, K. Vafai, The role of porous media in modeling flow and heat
transfer in biological tissues, Int. J. Heat Mass Transfer 46 (26) (2003) 4989–
5003.
[6] B. Khlebtsov, V. Zharov, A. Melnikov, V. Tuchin, N. Khlebtsov, Optical
amplification of photothermal therapy with gold nanoparticles and
nanoclusters, Nanotechnol. 17 (20, 28) (2006) 5167–5179.
[7] I.L. Maksimova, G.G. Akchurin, B.N. Khlebtsov, G.S. Terentyuk, G.G. Akchurin,
I.A. Ermolaev, A.A. Skaptsov, E.P. Soboleva, N.G. Khlebtsov, V.V. Tuchin, Near-
infrared laser photothermal therapy of cancer by using gold nanoparticles:
computer simulation and experiment, Medical Laser Appl. 22 (3) (2007) 199–
206.
[8] A. Nakayama, F. Kuwahara, A general bioheat transfer model based on the
theory of porous media, Int. J. Heat Mass Transfer 51 (11–12) (2008) 3190–
3199.
[9] N.G. Khlebtzov, L.A. Dykhman, Optical properties and biomedical applications
of plasmonic nanoparticles, J. Quant. Spectr. Radiat. Transfer 111 (1) (2010) 1–
35.
[10] X. Huang, M.A. El-Sayed, Gold nanoparticles; optical properties and
implementations in cancer diagnosis and photothermal therapy, J. Adv. Res.
1 (1) (2010) 13–28.
[11] W. Lu, C. Xiong, G. Zhang, Q. Huang, R. Zhang, J.Z. Zhang, C. Li, Targeted
photothermal ablation of murine melanomas with melanocyte-stimulating
hormone analog – conjugated hollow gold nanospheres, Clinical Cancer Res.
15 (3) (2009) 876–886.
[12] M.H. Niemz, in: Biological and Medical Physics Series, second ed., Laser-Tissue
Interactions. Fundamentals and Applications, Springer, Berlin, 2002.
[13] I.K. Tjahjono, Y. Bayazitoglu, Near-infrared light heating of a slab by embedded
nanoparticles, Int. J. Heat Mass Transfer 51 (7–8) (2008) 1505–1515.
[14] J. Vera, Y. Bayazitoglu, Gold nanoshell density variation with laser power for
induced hyperthermia, Int. J. Heat Mass Transfer 52 (3–4) (2009) 564–573.
[15] J. Vera, Y. Bayazitoglu, A note on laser penetration in nanoshell deposited
tissue, Int. J. Heat Mass Transfer 52 (13) (2009) 3402–3406.
[16] L.A. Dombrovsky, D. Baillis, Thermal Radiation in Disperse Systems: An
Engineering Approach, Begell House, New York and Redding (CT), 2010.
[17] L.A. Dombrovsky, D. Baillis, A simple physical approach to model spectral
radiative properties of semi-transparent dispersed materials, in: Proc. ASME/
JSME 8th Thermal Eng. Conf. (AJTEC-2011), 2011, Honolulu, Hawaii, USA, Paper
44011.
[18] J. Mobley, T. Vo-Dinh, Optical properties of tissue, in: T. Vo-Dinh (Ed.),
Biomedical Photonics Handbook, CRC Press, Boca Raton (FL), 2003, pp. 21–275.
[19] F.A. Duck, Physical Properties of Tissue: A Comprehensive Reference Book,
Acad. Press, San Diego, 1990.
[20] W. Cheong, S.A. Prahl, A.J. Welsh, A review of the optical properties of
biological tissues, IEEE J. Quant. Electron. 26 (12) (1990) 2166–2185.
[21] V.V. Tuchin, Lasers and Fiber Optics in Biomedical Science, Saratov Univ. Press,
Saratov, 1998. in Russian.
[22] D. Baillis, J.-F. Sacadura, Thermal radiation properties of dispersed media:
theoretical prediction and experimental characterization, J. Quant. Spectr.
Radiat. Transfer 67 (5) (2000) 327–363.
[23] J.-F. Sacadura, Thermal radiative properties of complex media: theoretical
prediction versus experimental identification, Heat Transfer Eng. 32 (9) (2011)
754–770.
[24] L.A. Dombrovsky, D. Baillis, J.H. Randrianalisoa, Some physical models used to
identify and analyze infrared radiative properties of semi-transparent
dispersed materials, J. Spectr. Dyn. 1 (2011) 7.
[25] P.R. Bargo, S.A. Prahl, T.T. Goodell, R.A. Sleven, G. Koval, G. Blair, S.L. Jacques, In
vivo determination of optical properties of normal and tumor tissue with
white light reflectance and an empirical light transport model during
endoscopy, J. Biomed. Opt. 10 (3) (2005) 034018.
[26] L.I. Chaikovskaya, O.V. Tsarjuk, I.V. Belotserkovsky, M.A. Vozmitel,
Determination of optical properties of tissues, J. Quant. Spectr. Radiat.
Transfer 112 (13) (2011) 2128–2133.
[27] L.G. Schulz, The optical constants of silver, gold, copper, and aluminum. I. The
absorption coefficient k, J. Opt. Soc. Am. 44 (5) (1954) 357–362.
[28] D.W. Lynch, W.R. Hunter, Comments on the optical constants of metals and an
introduction to the data for several metals, in: E.D. Palik (Ed.), Handbook of
Optical Constants of Solids, Acad. Press, Orlando (FL), 1985, pp. 286–295.
[29] L.G. Schulz, F.R. Tangherlini, The optical constants of silver, gold, copper, and
aluminum. I. The index of refraction n, J. Opt. Soc. Am. 44 (5) (1954) 362–368.
[30] I.H. Malitson, Interspecimen comparison of the refractive index of fused silica,
J. Opt. Soc. Am. 55 (10) (1965) 1205–1209.
[31] R. Kitamura, L. Pilon, M. Jonasz, Optical constants of silica glass from extreme
ultraviolet to far infrared at near room temperatures, Appl. Optics 46 (33)
(2007) 8118–8133.
[32] C.F. Bohren, D.R. Huffman, Absorption and Scattering of Light by Small
Particles, Wiley, New York, 1983.
[33] L.A. Dombrovsky, Thermal Radiation in Disperse Systems, Begell House, New
York, 1996.
[34] R.D. Averitt, S.L. Westcott, N.J. Halas, Linear optical properties of gold
nanoshells, J. Opt. Soc. Am. B 16 (10) (1999) 1824–1832.
[35] C. Loo, A. Lin, L. Hirsch, M.-H. Lee, J. Barton, N. Halas, J. West, R. Drezek,
Nanoshell-enabled photonics-based imaging and therapy of cancer, Technol.
Cancer Res. Treat. 3 (1) (2004) 33–40.
[36] E.R. Cleveland II, G. Schatz, K. Shuford, Optical properties of gold nanospheres,
Nanoscape 2 (1) (2005) 27–33.
[37] P. Mulvaney, Surface plasmon spectroscopy of nanosized metal particles,
Langmuir 12 (3) (1996) 788–800.
[38] R. Elganian, J.J. Storhoff, R.C. Mucic, R.L. Ltsinger, C.A. Mirkin, Selective
colorimertic detection of polynucleotides based on the distance-dependent
optical properties of gold nanoparticles, Science 277 (5329) (1997) 1078–
1081.
[39] M.M. Miller, A.A. Lazarides, Sensitivity of metal nanoparticle surface plasmon
resonance to the dielectric environment, J. Phys. Chem. B 109 (46) (2005)
21556–21565.
[40] H. Chen, X. Kou, Z. Yang, W. Ni, J. Wang, Shape- and size-dependent
refractive index sensitivity of gold nanoparticles, Langmuir 24 (10) (2008)
5233–5237.
[41] J.N. Anker, W.P. Hall, O. Lyandres, N.C. Shah, J. Zhao, R.P. Van Duyne, Biosensing
with plasmonic nanosensors, Nat. Mater. 7 (2008) 442–453.
[42] M.F. Modest, Radiative Heat Transfer, second ed., Academic Press, New York,
2003.
[43] J.R. Howell, R. Siegel, M.P. Mengüç, Thermal Radiation Heat Transfer, CRC
Press, New York, 2010.
[44] M.I. Mishchenko, L.D. Travis, A.A. Lacis, Multiple Scattering of Light by
Particles: Radiative Transfer and Coherent Backscattering, Cambridge Univ.
Press, New York, 2006.
[45] A. Fasano, D. Hömberg, D. Naumov, On a mathematical model for laser-
induced thermotherapy, Appl. Math. Model. 34 (12) (2010) 3831–3840.
 L.A. Dombrovsky et al. / International Journal of Heat and Mass Transfer 54 (2011) 5459–5469
[46] S. Banerjee, S.K. Sharma, Use of Monte Carlo simulations for propagation of
light in biomedical tissues, Appl. Opt. 49 (22) (2010) 4152–4159.
[47] B.H.J. McKellar, M.A. Box, The scaling group of the radiative transfer equation,
J. Atmos. Sci. 38 (5) (1981) 1063–1068.
[48] L. Dombrovsky, W. Lipiński, A combined P1 and Monte Carlo model for multi-
dimensional radiative transfer problems in scattering media, Comput. Thermal
Sci. 2 (6) (2010) 549–560.
[49] M.P. Çetingül, C. Herman, A heat transfer model of skin tissue for the detection
of lesions: sensitivity analysis, Phys. Medic. Biol. 55 (19) (2010) 5933–5951.
[50] M.P. Çetingül, C. Herman, Quantification of the thermal signature of a
melanoma lesion, Int. J. Therm. Sci. 50 (4) (2011) 421–431.
[51] M. Born, E. Wolf, Principles of Optics, seventh (expanded) ed., Cambridge Univ.
Press, New York, 1999.
[52] L.A. Dombrovsky, J.H. Randrianalisoa, W. Lipiński, D. Baillis, Approximate
analytical solution to normal emittance of semi-transparent layer of an
absorbing, scattering, and refracting medium, J. Quant. Spectr. Radiat. Transfer
112 (12) (2011) 1987–1994.
5469
[53] L. Dombrovsky, J. Randrianalisoa, D. Baillis, Modified two-flux approximation
for identification of radiative properties of absorbing and scattering media
from directional-hemispherical measurements, J. Opt. Soc. Am. A 23 (1) (2006)
91–98.
[54] H.H. Pennes, Analysis of tissue and arterial blood temperature in the resting
human forearm, J. Appl. Physiol. 1 (2) (1948) 93–122.
[55] M. de Greif, H.P. Kok, D. Correla, A. Bel, J. Crezee, Optimization in hyperthermia
treatment planning: the impact of tissue perfusion uncertainty, Med. Phys. 37
(9) (2010) 4540–4550.
[56] L.A. Dombrovsky, E.P. Yukina, A.V. Kolpakov, V.A. Ivanov, Procedure for
calculating the thermal destruction of phenolic carbon under the effect of
intensive infrared radiation, High Temp. 31 (4) (1993) 566–572.
[57] C. Freccero, F. Holmlund, S. Bornmyr, J. Castenfors, A.-M. Johansson, G.
Sundkvist, H. Svensson, P. Wollmer, Laser Doppler perfusion monitoring of
skin blood flow at different depths in finger and arm upon local heating,
Microvascular Res. 66 (3) (2003) 183–189.
[58] M.Z. Smirnov, A.E. Pushkareva, The effect of blood flow on the laser heating of
skin, Optics and Spectroscopy 99 (5) (2005) 843–845.