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Multiple Source Photothermal Therapy with External Contrast Agents for the Treatment of Breast Cancer: A Viability Study
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In this thesis, photothermal therapy is assessed as a treatment for tumours deep
inside the breast using near-infrared light and high absorbing external contrast agents,
which deliver the heat damage at the desired location. With the advent of light-absorbing
nanoparticles, there is a promising alternative to conventional breast cancer therapies
limiting the damage given to healthy tissue at the skin surface and enhancing the thermal
damage in cancer cells. There are some known limitations to this therapy, one of the
most important being the strong attenuation of light in biological tissue. Several authors
reported at best conflicting views on the therapy, with some claiming that indeed it is
possible performing it successfully up to a few centimetres. In contrast, other authors
claim that only at the surface these can be employed. The therapy’s success depends on
the optical properties and concentration of nanoparticles at the tumour location, but, to
my knowledge, there were no definitive studies that effectively tackle this issue from the
optics point of view. Hence, the studies developed in this thesis are in the pursuit of this
issue. Three protocols were developed; one to measure the optical properties of tissue,
another to produce optical phantoms with specific optical properties, and a numerical
simulation protocol to further the therapy’s effectiveness and possibly help design devices
and treatment protocols.
Several experiments have been developed to validate these protocols, and their results
have been compared with others already published. An INO® optical phantom with
known absorption and scattering coefficients was characterized by two experimental setups:
one developed by the company and another developed in this project. The results
of these two characterisations were compared to validate the protocol to measure optical
properties. The developed setup provides a reasonable estimate for the scattering properties
with an associated uncertainty of 7%, while the company’s associated uncertainty
was at 2%. Regarding the absorption setup measurement apparatus, the uncertainty
was in the same order of magnitude as the measured value for the developed apparatus.
The company’s apparatus also revealed a comparable uncertainty, thus, enhancing the
difficulty of measuring such small absorption coefficient’ values.
An optical phantom with a 9 mm thick inclusion placed at 5 mm from the surface
was produced, and a photothermal experiment was conducted on it to test the other protocols. Its irradiation lasted about 12 minutes. A thermocouple was placed at the interface
between the inclusion and the phantom for temperature measuring. Two optical
numerical models were implemented in this study, Monte Carlo and the diffusion approximation,
coupled with the classical heat diffusion equation to estimate the temperature
and compare with the experimental data. The Monte Carlo simulations outperformed
the diffusion approximation. The average percentage difference of the Monte Carlo and
diffusion approximation results compared to the experimental data was 4.5% and 61%.
The Pearson correlation coefficient between these models’ results and the experimental
data was 0.98 and 0.95, respectively. Additionally, the Monte Carlo and diffusion approximation
numerical models’ radial profile studies indicated an adequate distribution of
the former compared to what was expected from other studies.
Once the protocol of the numerical simulation was validated, a more realistic simulation
was conducted where a compressed breast geometry was considered with the
addition of skin, blood flow and a tumour 1 cm below the surface. A phantom with
breast, skin and blood flow properties coupled to the bioheat transfer equation was still
not studied in the community, to my knowledge. Additionally, several numerical irradiating
schemes were considered to enhance the absorption of light in depth. The breast
tissue was irradiated for two minutes in all of the irradiation schemes. The temperature in
the skin was high enough to produce damage, but the temperature increase at the tumour
was only 1 oC. This result contrasts clearly with other studies that show that at a depth
of 2 centimetres, a temperature increase of at least 15 oC can be achieved at 60 seconds
of illumination. One can conclude that photothermal therapy is indeed a treatment very
sensitive to breast optical properties. Other solutions have to be considered for breast
tissue of average optical properties to increase the effectiveness of in-depth photothermal
therapy using light-absorbing nanoparticles.
Descrição
Palavras-chave
Photothermal therapy hyperthermia diffusion approximation Monte Carlo gold nanoparticles numerical protocols