2.1 breast cancer model
In this research, the breast is modeled as a multi-layered hemisphere3, including the epidermis, papillary dermis, reticular dermis, fat, and gland containing a tumor. The radius of the breast is assumed to be 65 mm. Moreover, the tumor is considered to have an arbitrary shape including superficial and deep sections. The tumor's width varies from zero to 14.4 mm with a depth of 15 mm. Figure 1 shows a schematic diagram of the tissue and the tumor designed for the simulation. Tables 1 and 2 show the physical properties of tissue, tumor, and blood.
In the present simulation, the finite element method (FEM) solves all of the equations, and due to the luge number of elements in 3 dimensions and the limitations of the solver for calculating this model, the axial symmetry is considered for this geometry. In this paper, an ultrasound beam is produced by an acoustic transducer. Figure 2 shows the geometry of the tissue under the acoustic irradiation. It should be noted that in Fig. 2, both the tissue and the acoustic transducer are immersed in water. The transducer is a bowl-shaped element with a focal length of 62.64 mm, including an aperture with a radius of 35 mm and a hole with a radius of 10 mm in the center. The frequency of the transducer is 1 MHz20.
In this simulation, three lasers with a similar wavelength of 796 nm and various laser powers of 2W/cm2, 0.5W/cm2, and 0.25W/cm2 were utilized19. It should be mentioned here to avoid side effects, we use a more accurate laser with less power, and in real experiments, one laser can be used several times. The laser is continuous with an exposure time of 50 s and a cooling time of 20 s. Table 3 shows the optical properties of the tissue containing the tumor. Moreover, for controlling the produced temperature by ultrasound, it radiates to the tumor for the 60s and then turns off for 10s. This process continues for 10 min.
In addition, gold nanoparticles are added to the medium to increase the heating absorption. The nanoparticles are assumed to be homogeneously distributed in the tissue. In this simulation, nanoparticles' absorption and scattering coefficients are 121/cm and 5/cm, respectively21.
Table 1
Physical and thermal properties of tissue and tumor3.
Layer | Epidermis | Papillary Dermis | Reticular dermis | Fat | Gland | Muscle |
h(mm) | 0.1 | 0.7 | 0.8 | 5 | 43.4 | 15 |
k (W/ (m.K)) | 0.235 | 0.445 | 0.445 | 0.21 | 0.48 | 0.48 |
ρ (kg/\(\:{\mathbf{m}}^{3}\)) | 1200 | 1200 | 1200 | 930 | 1050 | 1100 |
c (J/ (kg. K)) | 3589 | 3300 | 3300 | 2770 | 3770 | 3800 |
\(\:{\varvec{Q}}_{0}(\mathbf{W}/{\mathbf{m}}^{3}\)) | 0 | 368.1 | 368.1 | 400 | 700 | 700 |
\(\:{\varvec{\omega\:}}_{\mathbf{b}}\) (1/s) | 0 | 0.0002 | 0.0013 | 0.0002 | 0.0006 | 0.0009 |
Table 2
Thermal properties of blood22.
property | value |
\(\:{\varvec{C}}_{\varvec{b}}(\varvec{J}/\:(\varvec{k}\varvec{g}.\:\varvec{K}\left)\right)\) | 4200 |
ρ (kg/m^3) | 1000 |
\(\:{\varvec{T}}_{\varvec{b}}\)(K) | 310.15 |
Table 3
The optical characteristics of the breast tissue23,24.
Layer | Epidermis | Papillary Dermis | Reticular dermis | Fat | Gland | Tumor |
\(\:{\varvec{\mu\:}}_{\varvec{a}}\)(1/m) | 19 | 19 | 19 | 6.5 | 6 | 6 |
\(\:{\varvec{\mu\:}}_{\varvec{s}}\)(1/m) | 834 | 834 | 834 | 1000 | 1275 | 5 |
α(dB/m) | 35 | 35 | 35 | 48 | 75 | 43 |
C(m/s) | 1510 | 1510 | 1510 | 1510 | 1510 | 1540 |
2.2 bioheat transfer
Thermal cancer treatment plays a significant role in the field of clinical applications. This kind of treatment causes an alteration of the tissue temperature to achieve the thermal ablation of tumors. In this procedure, an ultrasound transducer, a laser beam, or a microwave applies mechanical or light energy to tissues, leading to an elevation in temperature and, subsequently, causing the demise of cancerous cells25. The issue with the physical bioheat problems is evaluating the temperature profile and the fluence rate distribution in the tumorous region by knowing the governing initial and boundary conditions, geometry, heat sources, and the tissues' thermophysical and optical properties. Generally, in living tissues, blood perfusion and passage of blood modify the heat transfer. Furthermore, metabolic activity generates heat within the tissue. Therefore, an equation is needed to describe the heat transfer in tissue by considering the effects of both blood perfusion and metabolism.
This relation, widely known as Penne’s equation, was first established by Penne (1948) and Perl (1962)26,27,28 as below:
where, \(\:\rho\:\) is the density of the tissue, \(\:{c}_{P}\) is heat capacity, T is temperature, t is time, \(\:k\) is the thermal conductivity of tissue, \(\:{\rho\:}_{b}\) is blood density, \(\:{\omega\:}_{b}\) is blood perfusion, \(\:{c}_{b}\) is the heat capacity of the blood, \(\:{T}_{b}\) is the temperature of blood, \(\:{Q}_{met}\) indicates the metabolic heat source term, and \(\:{Q}_{s}\) is the external heat source. Here, there are two heat sources, laser and ultrasound, as follows:
$$\:{\mathbf{O}}_{\mathbf{s}}={\mathbf{Q}}_{\mathbf{L}}+{\mathbf{Q}}_{\mathbf{U}\mathbf{S}}$$
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In the following sections, each of these heat sources will be analyzed and then inserted into Eq. (1)
2.3 Interaction of laser and tissue
In this research, the laser beam is one of the main heat sources for tumor ablation. When an incident laser beam enters the medium in direction Ω, part of its intensity is absorbed, and another part of that is scattered in another direction, \(\:{\varOmega\:}^{{\prime\:}}\). The fraction that is absorbed is shown by \(\:{\sigma\:}_{a}\) I(Ω) and the scattered fraction is indicated by \(\:{\sigma\:}_{s}\) I(Ω), where \(\:{\sigma\:}_{a}\:\)and \(\:{\sigma\:}_{s}\) are absorption and scattering coefficients. One must solve the radiative transfer equation (RTE) to obtain the energy deposited at each point. For quasi-static conditions, which are met in the current study, RTE obeys the following Eq. 29:
$$\:\varvec{\Omega\:}.\nabla\:\mathbf{I}\left(\varvec{\Omega\:}\right)={\varvec{\sigma\:}}_{\mathbf{a}}{\mathbf{I}}_{\mathbf{b}}\left(\mathbf{T}\right)-\:\left({\varvec{\sigma\:}}_{\mathbf{a}}+{\varvec{\sigma\:}}_{\mathbf{s}}\right)\mathbf{I}\left(\varvec{\Omega\:}\right)\:+\:\frac{{\varvec{\sigma\:}}_{\mathbf{s}}}{4\varvec{\pi\:}}{\int\:}_{4\varvec{\pi\:}}\mathbf{I}\left({\varvec{\Omega\:}}^{\mathbf{{\prime\:}}}\right)\varvec{\upvarphi\:}({\varvec{\Omega\:}}^{\mathbf{{\prime\:}}},\:\varvec{\Omega\:})d{\varvec{\Omega\:}}^{\mathbf{{\prime\:}}}$$
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In the above equation, \(\:{I}_{b}\) denotes the blackbody intensity, which is derived from the Plank function, and ϕ (Ω′, Ω) signifies the probability that the beam will scatter from direction Ω′ toward the direction Ω. The last term of the right-hand side of this equation accounts for the portion of the radiative energy coming from all possible directions scattered toward the considered direction of propagation.
Generally, different methods such as the discrete ordinates method (DOM), P1-approximation, Rosseland approximation, and Beer-Lambert law are employed to solve the RTE. The P1 approximation stands out as one of the best and the most straightforward methods for solving the RTE, utilizing spherical harmonics with the capability of incorporating both isotropic and linear anisotropic scattering within its framework. In the P1-approximation method, incident radiation is defined as30:
$$\:\mathbf{G}={\int\:}_{4\varvec{\pi\:}}\mathbf{I}\left(\varvec{\Omega\:}\right)d\varvec{\Omega\:}$$
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and radiative heat flux is expressed as30:
$$\:{\mathbf{q}}_{\mathbf{r}}={\int\:}_{4\varvec{\pi\:}}\mathbf{I}\left(\varvec{\Omega\:}\right)\mathbf{d}\varvec{\Omega\:}$$
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By applying G and \(\:{q}_{r}\) to the RTE, it can be rewritten as below30:
\(\:\mathbf{I}\left(\mathbf{r},\widehat{\varvec{\Omega\:}}\right)=\:\frac{1}{4\varvec{\pi\:}}[\mathbf{G}\left(\mathbf{r}\right)\:+\:3\mathbf{q}\left(\mathbf{r}\right).\:\widehat{\varvec{\Omega\:}}\) ] (6)
When the laser beam irradiates into the medium, I in the equation will consist of the collimated laser beam entering the medium and the diffusion term emerging from scattering within the medium. As described by Modest and Tabanfar in Ref.30, in such scenarios, the impact of the external radiation field can be taken into account by introducing a source term into the diffusion terms. Hence, the simplified version of RTE emphasizes the diffusion of light due to the scattering phenomenon, and the source term directly incorporates the influence of the external collimated beam from the laser as bellow30:
\(\:\nabla\:\cdot\:{(\mathbf{D}}_{\mathbf{P}1}\nabla\:\mathbf{G})\) - \(\:{\varvec{\sigma\:}}_{\mathbf{a}}\)(G-4𝜋\(\:{\mathbf{I}}_{\mathbf{b}}\)) = 0 (7)
here, \(\:{D}_{P1}\)is diffusion coefficient in P1-approximation method and is defined as30:
$$\:{\mathbf{D}}_{\mathbf{P}1}=\:\frac{1}{3{\varvec{\sigma\:}}_{\mathbf{a}}+\:{\varvec{\sigma\:}}_{\mathbf{s}(3-{\mathbf{a}}_{1})}}$$
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where, \(\:{a}_{1}\) is the linear Legendre coefficient for the scattering phase function. This coefficient is related to anisotropy, so in the case of isotropic scattering, a1 equals zero.
Then, in the Penne equation, \(\:{Q}_{L}\) is the laser heat source based on the divergence of heat flux \(\:{q}_{r}\). That is because the radiative heat flux crossing an element calculated with an area normal to the direction of 𝞨 is a result of intensities incident from all directions, and it is the divergence of heat flux at any point that leads to increasing the temperature at that point. It should be stressed that once G is characterized at each point, ∇ · \(\:{q}_{r}\) can be found.
Moreover, adding gold nanoparticles significantly modifies the tissue's optical features. In this paper, gold nanoparticles' absorption and scattering coefficients are 121/cm and 0.5/cm, respectively21.
2.4 Interaction of ultrasound with tissue
As previously mentioned, ultrasound can be considered as a heat source. Here, the absorbed acoustic energy is calculated and used as the heat source,\(\:{Q}_{US}\), in Penne’s equation.
The propagation of the focused ultrasound waves as a time-independent problem follows the homogenous Helmholtz equation in 2D axisymmetric cylindrical coordinates as below20:
\(\:\frac{\partial\:}{\partial\:\mathbf{r}}\) [- \(\:\frac{\mathbf{r}}{{\varvec{\rho\:}}_{\mathbf{c}}}\left(\frac{\partial\:\mathbf{P}}{\partial\:\mathbf{r}}\right)\) ] + r \(\:\frac{\partial\:}{\partial\:\mathbf{z}}\) [- \(\:\frac{1}{{\varvec{\rho\:}}_{\mathbf{c}}}]-\) [ \(\:{\left(\frac{\varvec{\omega\:}}{{\mathbf{C}}_{\mathbf{C}}}\right)}^{2}]\frac{\mathbf{r}\mathbf{p}}{{\varvec{\rho\:}}_{\mathbf{c}}}\) = 0 (9)
where, r and z are the radial and axial coordinates, p is the acoustic pressure, and 𝜔 is the angular frequency. \(\:{\rho\:}_{c}\) is density and \(\:{C}_{C}\) is the speed of sound, which is also complex-valued to account for the material's damping properties.
The Helmholtz equation assumes that the acoustic wave propagation is linear and that the amplitude of the shear waves in the tissue domain is much smaller than that of the pressure waves. Therefore, nonlinear effects and shear waves are neglected.
The acoustic intensity field can also be derived from the acoustic pressure field. Finally, by knowing the acoustic intensity field, \(\:{Q}_{US\:}\) is calculated as below20:
\(\:{\mathbf{Q}}_{\mathbf{U}\mathbf{S}}\) = 2\(\:{\varvec{\alpha\:}}_{\mathbf{A}\mathbf{B}\mathbf{C}}\)I = 2\(\:{\varvec{\alpha\:}}_{\mathbf{A}\mathbf{B}\mathbf{C}}\left|\mathbf{Re}\left(\frac{1}{2}\mathbf{p}\mathbf{v}\right)\right|\) (10)
here, \(\:{\alpha\:}_{ABC}\), I, p, and v are the attenuation coefficient, acoustic intensity magnitude, acoustic pressure, and acoustic particle velocity vector, respectively. Furthermore, the attenuation coefficient of tissue with and without gold nanoparticles is 70 dB/m and 43 dB/m, respectively24.
2.5 Thermal damage
An important concern in research about bioheat transfer is accurate and appropriate thermal damage of the diseased tissues without destroying the neighboring healthy tissues during tumor treatment. Several investigations have demonstrated that tissue damage depends on the temperature and exposure time. It should be mentioned that as tissue temperature increases, the elapsed time necessary to achieve the threshold of damages decreases. The progression of the thermal injury can be reasonably approximated by the Arrhenius equation. This relation is usually utilized for illustrating the rate of the irreversible heating damage of the biological tissues31,32:
$$\:\varvec{\Omega\:}\left(\mathbf{t}\right)\:=\:{\int\:}_{0}^{\mathbf{t}}{\mathbf{A}}^{\frac{\varvec{\Delta\:}\mathbf{E}}{{\mathbf{e}}^{\mathbf{R}\mathbf{T}}}}d\mathbf{t}$$
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In the above equation, \(\:\varOmega\:\)(t) indicates the degree of tissue injury, R is the universal gas constant, A is the frequency factor for kinetic expression, and ¬E is the activation energy for irreversible damage reaction. The critical value of \(\:\varOmega\:\) = 1 is the point when thermal necrosis occurs. Generally, two parameters of A and \(\:\varDelta\:\)E depend on the type of tissue. Here, for the breast tissue A and \(\:\varDelta\:E\) are 1.18×\(\:{10}^{44}\) and 3.02×\(\:{10}^{55}\), respectively3.