Heat transfer phenomenon and optical interaction during nanoparticle assisted thermal therapy

Abstract

Cancer is the second most leading cause of deaths in the world after heart disease. Treatment strategy for cancer varies as per the type and origin of the disease. Widely used standard cancer treatment modalities are radiotherapy, chemotherapy and surgery have significant side effects affecting the quality of life of a cancer patient and can be even life threatening in some cases. Other secondary treatment methods viz. cryotherapy, gene therapy, hyperthermia/thermal ablation, Radio-frequency ablation, photodynamic therapy and targeted cancer therapies etc are under investigation for long term side effects and survival rates. Therefore, there exists a definite scope of improving the cancer treatment methods for cancer so that these can lead to lesser side effects and be affordable to the society. In the therapeutics domain related to thermal treatment, recently nanoparticle assisted thermal therapy is being explored as a promising future treatment for cancer. This therapy involves delivering the nanoparticles to a tumour and then irradiating the tumour (within therapeutic window) to generate heat to kill the cancerous cells. The therapeutic window refers to the wavelength band of 600 nm to 1300 nm in which tissues absorb almost zero radiation. Such therapy, first reported in 2003, would allow doctors to specifically treat tumours without damaging nearby healthy tissues, which is a significant side effect of standard cancer treatment modalities. Regarding the choice of nanoparticles - gold nanoshells and nanorods hold promise as their optical properties can be tuned by modifying the size to suit the therapeutic window. Radiation interaction of tissue/tumour and nanoparticles involves two phenomena. Firstly, radiation interaction of a bare tissue decides the penetration depth of radiation within the tissue so that it can be absorbed by embedded nanoparticles. Secondly, interaction of nanoparticles with radiation decides the amount of energy absorbed by nanoparticles, which is responsible for thermal ablation. The present work addresses the optical interaction and heat transfer phenomenon to improve the understanding towards the nanoparticle assisted thermal therapy. Firstly the role of optical coefficients of nanoparticles (embedded within a tumour) and healthy tissue sparing characteristics are analyzed numerically. It is shown that a tumour region can be made highly absorbing by selecting nanoparticles with suitable optical coefficients and criteria for size selection of gold nanorods is specified. Also it is shown that the damage to healthy tissues surrounding a tumour can be curtailed by proper selection of the irradiation parameters, size and volume fraction of nanoparticles. Results show that it is possible to selectively heat a tumour and spare healthy tissues within 2-3 mm of its surroundings. Since the nanoparticles act as source of heat within the tumour, so their spatial distribution critically governs the thermal ablation extent. This issue has also been also addressed in the present work by considering non-uniform distribution of nanoparticles within a tumour. The analysis shows that distribution of nanoparticles into the periphery of tumour resulted in desired thermal ablation conditions in the whole of considered tumour. So, a peripheral distribution of nanoparticles seems to be desirable, which contradicts the conventional wisdom of having nanoparticles uniformly distributed within the tumour. This finding is quite important because a non-uniform nanoparticle distribution is guaranteed from almost every practical nanoparticle delivery mechanism. Next, the influence of blood perfusion variability within a tumour and the surrounding healthy tissue was investigated numerically. Spatiotemporal variability of blood perfusion for various perfusion conditions was considered and the corresponding thermal damage zones were evaluated to understand the influence of blood perfusion. The temporal variation of blood perfusion is incorporated based on vascular stasis i.e. damage to the blood vessels. The spatial variation of the perfusion rate is incorporated by comparing a homogenously perfused tumour with a heterogeneously perfused tumour under similar irradiation conditions. It was found that for the moderately and highly perfused tumours, the consideration of constant perfusion (during the therapy) underpredicts the thermal damage zone. So relying on the constant perfusion based thermal damage results can lead to significant damage of the surrounding healthy tissue. It is concluded that for effective therapy, the therapeutic parameters need to be selected based on perfusion dynamics to overcome the heat loss due to blood perfusion. Lastly, the heat confinement characteristics were experimentally investigated using agarose gel as a tissue mimic. The experiments were conducted on agarose gel phantoms with and without the presence of embedded gold nanoparticles. The developed numerical model was validated against these gel experiments in zero blood perfusion and metabolism case. The measurements were then extended to a real tumour-tissue by taking into account blood perfusion and metabolic heat generation. Also, radial heat confinement experiment showed that there is remarkable symmetry in the radial temperature measurements and thus heat confinement for the circular shaped beam irradiation. This leads to an important indication that it may be feasible to heat an irregular shaped tumour through suitable beam shaping techniques. Overall, the experimental and numerical investigations of this work confirm the ability of nanoparticles to confine the heat and thus thermally damage a region of interest. The results demonstrate the control of thermal ablation temperature within ≤ 3 mm adjacent to the nanoparticle embedded region.