Recently, hyperthermia has been investigated as an alternate therapy for the treatment of tumors. The present project explored the feasibility of preferential hyperthermia as a method of treating deep seated tumors. The overall goal of this research was to determine theoretically if preferential heating could be used to attain the desired thermal dose (DTD) for a two cm diameter tumor. The simulations in this work show that, when using a single silicon carbide insert, the model cannot provide enough energy for an entire 2 cm diameter tumor to receive the DTD. However, when using an enhanced design model with multiple (4) silicon carbide inserts, the DTD could be attained in a tumor up to 3.5 cm in diameter. This study involved using the commercially available software package ANSYS 7.0 program to model a spherical 2 cm tumor, assuming the tumor is located in deep tissue with a constant perfusion rate and no major blood vessels nearby. This tumor was placed in the center of a cube of healthy tissue. To achieve the preferential heating of the tumor, a silicon carbide insert was placed in the center of the tumor and microwave energy was applied to the insert (in the form of volumetric heating). The thermal modeling of this system was based on the Pennes Bioheat equation with a maximum temperature limitation of of 80 ºC. The Thermal Dose Analyzer software program was used to evaluate the results of the thermal simulations (from ANSYS) to determine if the DTD had been attained. Additional enhanced design models were also examined. These models include 2 cm and 4 cm tumors with four silicon carbide inserts symmetrically placed about the tumor and a 4 cm tumor model using a single silicon carbide insert with antennae attached to the insert to increase energy distribution to the tumor. The simulations show that only the enhanced design cases with four silicon carbide inserts can achieve the DTD for an entire 2 cm tumor. / Master of Science

Hyperthermia is a cancer treatment modality that raises cancerous tissue to cytotoxic temperature levels for roughly 30 to 45 minutes. Hyperthermia treatment planning refers to the use of computational models to optimize the heating protocol to be used in a hyperthermia treatment. This thesis presents a method to optimize a hyperthermia treatment heating protocol. An algorithm is developed which recovers a heating protocol that will cause a desired amount of thermal damage within a region of tissue. The optimization algorithm is validated experimentally on an albumen tissue phantom. The transient temperature distribution within the region is simulated using a two-dimensional, finite-difference model of the Pennes bioheat equation. The relationship between temperature and time is integrated to produce a damage field according to two different models; Henriques'' model and the thermal dose model (Moritz and Henriques (1947)), (Sapareto and Dewey (1984)). A minimization algorithm is developed which re duces the value of an objective function based on the squared difference between an optimal and calculated damage field. Either damage model can be used in the minimization algorithm. The adjoint problem in conjunction with the conjugate gradient method is used to minimize the objective function of the control problem. The flexibility of the minimization algorithm is proven experimentally and through a variety of simulations. With regards to the validation experiment, the optimal and recovered regions of permanent thermal damage are in good agreement for each test performed. A sensitivity analysis of the finite difference and damage models shows that the experimentally-obtained extent of damage is consistently within a tolerable error range. Excellent agreement between the optimal and recovered damage fields is also found in simulations of hyperthermia treatments on perfused tissue. A simplified and complex model of the human skin were created for use within the algorithm. Minimizations using both the Henriques'' model and the thermal dose model in the objective function are performed. The Henriques'' damage model was found to be more desirable for use in the minimization algorithm than the thermal dose model because it is less computationally intensive and includes a mechanism to predict the threshold of permanent thermal damage. The performance of the minimization algorithm was not hindered by adding complexity to the skin model. The method presented here for optimizing hyperthermia treatments is shown to be robust and merits further investigation using more complicated patient models. / Master of Science

Submitted by Erika Demachki (erikademachki@gmail.com) on 2017-05-29T17:22:24Z No. of bitstreams: 2 Tese - Harley Fernandes Rodrigues - 2017.pdf: 14917308 bytes, checksum: 98bd396b4a6b5e7839b6b8ff0fd12102 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-05-30T10:44:17Z (GMT) No. of bitstreams: 2 Tese - Harley Fernandes Rodrigues - 2017.pdf: 14917308 bytes, checksum: 98bd396b4a6b5e7839b6b8ff0fd12102 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-05-30T10:44:17Z (GMT). No. of bitstreams: 2 Tese - Harley Fernandes Rodrigues - 2017.pdf: 14917308 bytes, checksum: 98bd396b4a6b5e7839b6b8ff0fd12102 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-04-19 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / In this thesis a methodology of real-time monitoring of magnetic hyperthermia (HM) in vivo was developed in the murine tumor model Sarcoma 180 using infrared thermography technique. Magnetic nanoparticles (NPM) consisted of Mn ferrites capable of generating heat at low magnetic field amplitude at the 300 kHz frequency within the safety limit determined by Atkinson. It has been shown that the apparent surface temperature value measured with the infrared camera underestimates the real skin temperature value of the mice if the camera objective does not form an angle 0 ° with the normal direction to the animal's skin in the region of interest on the tumor, with the error reaching more than 7.0 ° C (for 60 °). A new theoretical model to estimate the error in the temperature of curved surfaces was developed and proved valid even in the case where the surface temperature diverges significantly from the environment. Preclinical treatment results indicated a complete remission condition in animal that was submitted to 150 min of hyperthermia and other cases with partial remission, suggesting that biological response analyzes need to be done in a long time (> 60 days). Measurements of the intratumoral temperature monitored by three fiber-optic thermometers during the therapeutic procedure of HM with NPM indicated an inhomogeneous heat delivery within the tumor. Additionally, a new methodology for calculating the thermal dose (CEM43) evaluated at the surface, considering each pixel of the thermographic image as a thermometer in the tumor region, indicated that the value T10(t) of the temperature detected in vivo at the surface of the skin over subcutaneous tumors can report, with an error of the order of 5%, the mean intratumoral temperature value during the therapeutic procedure of HM. / Nesta tese foi desenvolvida uma metodologia de monitoramento em tempo real da hipertermia magnética (HM) in vivo no modelo tumoral murino Sarcoma 180 utilizando a técnica de termografia por infravermelho. As nanopartículas magnéticas (NPM) consistiam de ferritas de Mn capazes de gerar calor em baixa amplitude de campo magnético, na frequência de 300 kHz, dentro do limite de segurança determinado por Atkinson. Foi demonstrado que o valor da temperatura superficial aparente medido com a câmera de infravermelho subestima o valor da temperatura real da pele dos camundongos se a objetiva da câmera não formar um ângulo 0° com a direção normal à pele do animal na região de interesse sobre o tumor, podendo o erro chegar a mais do que 7,0 °C (para 60°). Um novo modelo teórico para estimar o erro na temperatura de superfícies curvas foi desenvolvido e se mostrou válido inclusive para o caso em que a temperatura superficial diverge significativamente da ambiente. Resultados pré-clínicos do tratamento indicaram uma situação de remissão completa em animal que passou por 150 min de hipertermia e outros casos com remissão parcial, sugerindo que análises de resposta biológica precisam ser feitas em longo tempo (> 60 dias). Medidas da temperatura intratumoral monitorada por três termômetros de fibra-óptica durante o procedimento terapêutico de HM com NPM indicaram uma entrega de calor não homogênea dentro do tumor. Adicionalmente, uma nova metodologia para o cálculo da dose térmica (CEM43) avaliada na superfície, considerando cada pixel da imagem termográfica como um termômetro na região do tumor, indicou que o valor de T10(t) da temperatura detectada in vivo na superfície da pele sobre tumores subcutâneos pode informar, com um erro da ordem de 5%, o valor da temperatura média intratumoral durante o procedimento terapêutico de HM.