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Optimizing diffusion time prior to probe-mediated microwave heating of injected nanoparticles for hyperthermia treatment of tumors

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Localized tumor hyperthermia therapy is a treatment that involves heating cancerous tissue to temperatures that result in tumor cell necrosis, while preventing damage to surrounding healthy tissue. Hyperthermia therapy treatments reported in the literature have shown that nanoparticles can be injected into a targeted tumor, allowing specific regions to undergo treatment and reducing the healthy tissue that is affected as well. Previous studies have shown that when the nanoparticles absorb specific wavelengths of radiation, they undergo resonance and emit heat. Thus, the targeted tumor can be heated through the actions of both tissue absorption, and heat emitted by the excited nanoparticles. This additional heat due to nanoparticles within a tumor can facilitate tumor heating over a given time-frame so as to prevent damage to surrounding healthy tissue. Our project aimed to investigate the efficacy of utilizing injectable ferromagnetic nanoparticles (with the properties of γ-hematite nanoparticles) to facilitate microwave heating of cancerous tissue.

The first stage of our project was modeling the precise delivery and dispersion of a volume of nanoparticles in a targeted cancerous tissue. To do this, we built a 1D radially symmetric computational model in COMSOL to represent a tumor, and we computed the diffusion profile of the nanoparticles in this domain over the time directly after injection. Next, we built a 2D axisymmetric computational domain in COMSOL to model the heat treatment. This model included heating of the tumor tissue with a microwave probe, and then coupled this heating with heating due to the nanoparticle concentration in the tissue. Computing the heat and energy profiles for this heating model allowed us to then determine the optimal time after injection to begin the heat treatment to maximize cancer cell death, but minimize damage to healthy tissue. The optimal time was determined as the time when all cancerous tissue temperature had been raised above 43 °C, while the maximum surrounding healthy tissue temperature was still below 43 °C. In conjunction with finding the optimal heating interval, our goal was to also find the optimized injection nanoparticle concentration, nanoparticle diffusion time, and microwave radiation power level.

Computed temperature profiles that took into account heating due to the presence of nanoparticles within the tumor computational domain showed only a slightly larger proportion of the tumor domain reaching temperatures in excess of 43 °C than could be achieved when heating is due to radiation absorption by the tissue alone. Our conclusion is that, within the model, the nanoparticles are indeed absorbing microwave radiation, but they are not subsequently emitting as much heat as was expected. As they are absorbing radiation, they are blocking the passage of energy into the tissue areas directly surrounding the nanoparticles. Without the nanoparticles in the tumor domain, the microwave radiation can be absorbed entirely by the tissue, resulting in more desirable temperature profiles. Thus, our model as implemented does not demonstrate that injecting γ-hematite nanoparticles into a tumor facilitates probe-mediated microwave heating of said tumor. However, several changes could be made to our model to achieve more desirable results. For example, if the nanoparticles were injected so as to enclose the tumor targeted for destruction, then they would effectively create a barrier for microwave radiation to pass through, thus restricting the radiation heating primarily to the enclosed tumor region. Alternatively, the ferromagnetic nanoparticles could be magnetically tuned (using a varying magnetic field) during microwave radiation so that they do actually undergo resonance significantly, resulting in greater heat emission and desirable temperature profiles. Regardless, we did successfully model probe-mediated microwave radiation of a tumor for hyperthermia treatment using a complete electromagnetism module in COMSOL, something that has never been done before in this course. We found the optimum microwave probe power level and radiation time required to maximize tumor death while minimizing healthy tissue damage in our model. It follows that localized tumor hyperthermia therapy that uses a microwave-emitting probe for tumor destruction can be modeled and fine-tuned using COMSOL. With appropriate model modifications, it could be shown that ferromagnetic nanoparticles can be used to direct the microwave heating in the targeted region. Mass transfer and heat transfer models similar to the ones used in this project can be built with specific tumor geometries, tissue properties, and probe properties, and such models can be used to plan clinical applications of using probe-mediated microwave heating of cancerous tissue.

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2013-05-30

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