In treating cancer, a primary consideration is the target specificity of the treatment. This is a measure of the treatment dose that the cancerous (target) tissue receives compared to the dose that healthy tissue receives. Nanoparticle (NP) based treatments offer many advantages for target specificity compared to other forms of treatment due to their ability to selectively target tumors. One benefit of using magnetic NPs is their ability to release heat, which can both sensitize tumors to other forms of treatment as well as damage the tumor. The work here aims to incorporate a broad range of relevant physics into a comprehensive model. NP aggregation is known to be a large source of uncertainty in these treatments, thus a framework has been developed that can incorporate the effects of aggregation on NP diffusion, NP heat release, temperature rise, and overall thermal damage. To quanitify thermal damage in both healthy tissue and tumor tissue, the Cumulative Equivalent Minutes at 43 textcelsius~model is used. The Pennes bioheat equation is used as the governing equation for the temperature rise and included in it is a source heating term due to the NPs. NP diffusion and aggregation are simulated via a random walk process, with a probability of aggregation determining if nearest neighbor particles aggregate at each time step. Additionally, models are developed that attempt to incorporate aggregation effects into NP heat dissipation, though each proves to only be accurate when there is little aggregation occurring. In this work, verification analyses are done for each of the above areas and, at minimum, qualitatively accurate results have been achieved. Verification results of this work show that aggregation can be neglected at concentrations on the order of $100~nM$ or less. This however only serves as a rough estimation and further work is needed to gain a better quantitative understanding of the effects of NP concentration on aggregation. Using this concentration as a limitation, results are presented for a variety of tumor sizes and concentration distributions. Because this work incorporates a variety of physics and numerical methods into a single encompassing model, depth and physical accuracy in each area (bio-heat transfer, diffusion via random walk, NP energy dissipation, and aggregation) have been somewhat limited. This does however provide a framework in which each of the above areas can be further developed and their effects examined in the overall course of treatment. / Master of Science

No description available.

The primary purpose of this work was to evaluate the capability of nanoparticles to transform electromagnetic energy at microwave frequencies into therapeutic heating. Targeted nanoparticles, in conjunction with microwave irradiation, can increase the temperatures of the targeted area over the peripheral region. Therefore, to become clinically viable, microwave absorbing nanoparticles must first be identified, and a system to monitor the treatment must be developed. In this study, ultrasound temperature imaging was used to monitor the temperature of deep lying structures. First, a material-dependent quantity to correlate the temperature induced changes in ultrasound images (i.e. apparent time shifts) to differential temperatures was gathered for a tissue-mimicking phantom, porcine longissimus dorsi muscle, and porcine fat. Then microwave nanoabsorbers were identified using an infrared radiometer. The determined nanoabsorbers were then injected into ex-vivo porcine longissimus dorsi muscle tissue. Ultrasound imaging frames were gathered during microwave treatment of the inoculated tissue. Finally, the ultrasound frames were analyzed using the correlation between temperature and apparent shifts in ultrasound for porcine muscle tissue. The outcome was depth-resolved temperature profiles of the ex-vivo porcine muscle during treatment. The results of this study show that magnetite is a microwave nanoabsorber that increases the targeted temperature of microwave hyperthermia treatments. Overall, there is clinical potential to use microwave nanoabsorbers to increase the efficiency of microwave hyperthermia treatments. / text

Scientific research in areas of physics, chemistry, and biology traditionally depends purely on experimental and theoretical methods. Recently numerical simulation is emerging as the third way of science discovery beyond the experimental and theoretical approaches. This work describes some general procedures in numerical computation, and presents several applications of numerical modeling in bioheat transfer and biomechanics, jet diffusion flame, and bio-molecular interactions of proteins in blood circulation. A three-dimensional (3D) multilayer model based on the skin physical structure is developed to investigate the transient thermal response of human skin subject to external heating. The temperature distribution of the skin is modeled by a bioheat transfer equation. Different from existing models, the current model includes water evaporation and diffusion, where the rate of water evaporation is determined based on the theory of laminar boundary layer. The time-dependent equation is discretized using the Crank-Nicolson scheme. The large sparse linear system resulted from discretizing the governing partial differential equation is solved by GMRES solver. The jet diffusion flame is simulated by fluid flow and chemical reaction. The second-order backward Euler scheme is applied for the time dependent Navier-Stokes equation. Central difference is used for diffusion terms to achieve better accuracy, and a monotonicity-preserving upwind difference is used for convective ones. The coupled nonlinear system is solved via the damped Newton's method. The Newton Jacobian matrix is formed numerically, and resulting linear system is ill-conditioned and is solved by Bi-CGSTAB with the Gauss-Seidel preconditioner. A novel convection-diffusion-reaction model is introduced to simulate fibroblast growth factor (FGF-2) binding to cell surface molecules of receptor and heparan sulfate proteoglycan and MAP kinase signaling under flow condition. The model includes three parts: the flow of media using compressible Navier-Stokes equation, the transport of FGF-2 using convection-diffusion transport equation, and the local binding and signaling by chemical kinetics. The whole model consists of a set of coupled nonlinear partial differential equations (PDEs) and a set of coupled nonlinear ordinary differential equations (ODEs). To solve the time-dependent PDE system we use second order implicit Euler method by finite volume discretization. The ODE system is stiff and is solved by an ODE solver VODE using backward differencing formulation (BDF). Findings from this study have implications with regard to regulation of heparin-binding growth factors in circulation.

O objetivo deste trabalho é o desenvolvimento de um modelo matemático dos sistemas térmico e respiratório humanos que permita, a partir das condições do ambiente e do nível de atividade física, determinar a distribuição da temperatura e das concentrações de oxigênio e dióxido de carbono ao longo do corpo. No modelo representou-se o corpo humano dividido em quinze segmentos: cabeça, pescoço, tronco, braços, antebraços, mãos, coxas, pernas e pés. Cada segmento contém um compartimento arterial e um compartimento venoso, os quais representam os grandes vasos. O sangue nos pequenos vasos foi considerado juntamente com os tecidos músculo, gordura, pele, osso, cérebro, pulmão, coração e vísceras. Os gases O2 e CO2 são transportados pelo sangue e armazenados nos tecidos, dissolvidos e reagidos quimicamente. Nos tecidos ocorre metabolismo, que consome oxigênio e produz dióxido de carbono e calor. A pele troca calor com o ambiente por condução, convecção, radiação e evaporação. O trato respiratório o faz pela ventilação, por convecção e evaporação. Nos pulmões ocorre transferência de massa, por difusão entre um compartimento alveolar e diversos compartimentos capilares pulmonares. Para modelar o transporte de massa e o transporte de calor nos tecidos foram usadas duas formas distintas. No caso da transferência de massa, os tecidos foram representados por compartimentos nos segmentos modelados. No caso da transferência de calor, foram representados por camadas nos segmentos, sendo que estes ora têm a geometria de um cilindro (seção transversal circular), ora a de um paralelogramo no caso das mãos e dos pés. O sistema regulador do corpo humano foi divido em quatro formas de atuação: metabolismo, circulação, ventilação e sudorese. O metabolismo varia com o calafrio (que depende da temperatura corporal) e a atividade física; a circulação depende da concentração dos gases no corpo, da temperatura e do metabolismo; a ventilação, da concentração dos gases; a sudorese, da temperatura. Para solucionar as equações diferenciais do modelo foram usados métodos numéricos implícitos. As equações diferenciais parciais foram discretizadas pelo método dos volumes finitos. Comparações com trabalhos experimentais encontrados na literatura mostraram que o modelo é adequado para representar variações climáticas, exposições a quantidades reduzidas de oxigênio e elevadas de dióxido de carbono, e situações de exercício físico. Outros resultados gerados pelo modelo demonstraram que acidentes de descompressão tornam-se mais severos quando associados à queda da temperatura ambiente, por causa do aumento do consumo de O2 pelo calafrio. Este também aumenta o risco de uma intoxicação por CO2, devido ao aumento da sua produção. O modelo mostrou-se ainda capaz de prever diversas interações entre os sistemas térmico e respiratório, como a diminuição da temperatura corpórea pelo aumento da ventilação (que depende das concentrações de O2 e CO2), ou a diminuição da pressão parcial dos gases nos segmentos mais extremos, em consequência do efeito da temperatura na capacidade do sangue de transportá-los. / The aim of this work is the development of a mathematical model of the human body respiratory and thermal systems. The model allows the determination of the temperature, oxygen and carbon dioxide distributions, depending on the ambient conditions and the physical activity level. The human body was divided into 15 segments: head, neck, trunk, arms, forearms, hands, thighs, legs and feet. Each segment contains an arterial and a venous compartment, representing the large vessels. The blood in the small vessels is considered together with the tissues muscle, fat, skin, bone, brain, lung, heart and viscera. The gases O2 and CO2 are transported by the blood and stored by the tissues dissolved and chemically reacted. Metabolism takes place in the tissues, where oxygen is consumed generating carbon dioxide and heat. The skin exchanges heat with the environment by conduction, convection, radiation and evaporation. The respiratory tract exchanges heat by convection and evaporation. In the lungs, mass transfer happens by diffusion between an alveolar compartment and several pulmonary capillaries compartments. Two different forms were used to model the transport of mass and heat in the tissues. For the mass transfer, the tissues were represented by compartments inside the segments. For the heat transfer, the tissues were represented by layers inside the segments, which have the geometry of a cylinder (circular cross-section) or a parallelogram hands and feet. The regulatory systems were divided into four mechanisms: metabolism, circulation, ventilation and sweating. The metabolism is modified by the shivering (which depends on the body temperature) and the physical activity; the circulation depends on the body gas concentrations, the temperature and the metabolism; the ventilation depends on the gas concentrations; the sweating depends on the temperature. Implicit methods were used to solve the differential equations. The discretization of the partial differential equations was obtained applying the finite volume method. Comparisons with experimental works found in literature show that the model is suitable to represent the exposure to cold and warm ambients, to low amounts of oxygen, to carbon dioxide, and physical activity. Other results of the developed model show that decompression accidents become more severe when associated to low ambient temperatures, because of the increase in the O2 consumption by shivering. The shivering also increases the danger of a CO2 intoxication, due to the increase of its production. The model showed as well the capacity to represent the several interactions between the thermal and respiratory systems, as the decrease of the body temperature because of the increase in the ventilation (which depends on the O2 and CO2 concentrations), or the decrease of the O2 and CO2 partial pressures in the more extreme segments, consequence of the temperature effect on their blood transport capacity.

O objetivo deste trabalho é o desenvolvimento de um modelo matemático dos sistemas térmico e respiratório humanos que permita, a partir das condições do ambiente e do nível de atividade física, determinar a distribuição da temperatura e das concentrações de oxigênio e dióxido de carbono ao longo do corpo. No modelo representou-se o corpo humano dividido em quinze segmentos: cabeça, pescoço, tronco, braços, antebraços, mãos, coxas, pernas e pés. Cada segmento contém um compartimento arterial e um compartimento venoso, os quais representam os grandes vasos. O sangue nos pequenos vasos foi considerado juntamente com os tecidos músculo, gordura, pele, osso, cérebro, pulmão, coração e vísceras. Os gases O2 e CO2 são transportados pelo sangue e armazenados nos tecidos, dissolvidos e reagidos quimicamente. Nos tecidos ocorre metabolismo, que consome oxigênio e produz dióxido de carbono e calor. A pele troca calor com o ambiente por condução, convecção, radiação e evaporação. O trato respiratório o faz pela ventilação, por convecção e evaporação. Nos pulmões ocorre transferência de massa, por difusão entre um compartimento alveolar e diversos compartimentos capilares pulmonares. Para modelar o transporte de massa e o transporte de calor nos tecidos foram usadas duas formas distintas. No caso da transferência de massa, os tecidos foram representados por compartimentos nos segmentos modelados. No caso da transferência de calor, foram representados por camadas nos segmentos, sendo que estes ora têm a geometria de um cilindro (seção transversal circular), ora a de um paralelogramo no caso das mãos e dos pés. O sistema regulador do corpo humano foi divido em quatro formas de atuação: metabolismo, circulação, ventilação e sudorese. O metabolismo varia com o calafrio (que depende da temperatura corporal) e a atividade física; a circulação depende da concentração dos gases no corpo, da temperatura e do metabolismo; a ventilação, da concentração dos gases; a sudorese, da temperatura. Para solucionar as equações diferenciais do modelo foram usados métodos numéricos implícitos. As equações diferenciais parciais foram discretizadas pelo método dos volumes finitos. Comparações com trabalhos experimentais encontrados na literatura mostraram que o modelo é adequado para representar variações climáticas, exposições a quantidades reduzidas de oxigênio e elevadas de dióxido de carbono, e situações de exercício físico. Outros resultados gerados pelo modelo demonstraram que acidentes de descompressão tornam-se mais severos quando associados à queda da temperatura ambiente, por causa do aumento do consumo de O2 pelo calafrio. Este também aumenta o risco de uma intoxicação por CO2, devido ao aumento da sua produção. O modelo mostrou-se ainda capaz de prever diversas interações entre os sistemas térmico e respiratório, como a diminuição da temperatura corpórea pelo aumento da ventilação (que depende das concentrações de O2 e CO2), ou a diminuição da pressão parcial dos gases nos segmentos mais extremos, em consequência do efeito da temperatura na capacidade do sangue de transportá-los. / The aim of this work is the development of a mathematical model of the human body respiratory and thermal systems. The model allows the determination of the temperature, oxygen and carbon dioxide distributions, depending on the ambient conditions and the physical activity level. The human body was divided into 15 segments: head, neck, trunk, arms, forearms, hands, thighs, legs and feet. Each segment contains an arterial and a venous compartment, representing the large vessels. The blood in the small vessels is considered together with the tissues muscle, fat, skin, bone, brain, lung, heart and viscera. The gases O2 and CO2 are transported by the blood and stored by the tissues dissolved and chemically reacted. Metabolism takes place in the tissues, where oxygen is consumed generating carbon dioxide and heat. The skin exchanges heat with the environment by conduction, convection, radiation and evaporation. The respiratory tract exchanges heat by convection and evaporation. In the lungs, mass transfer happens by diffusion between an alveolar compartment and several pulmonary capillaries compartments. Two different forms were used to model the transport of mass and heat in the tissues. For the mass transfer, the tissues were represented by compartments inside the segments. For the heat transfer, the tissues were represented by layers inside the segments, which have the geometry of a cylinder (circular cross-section) or a parallelogram hands and feet. The regulatory systems were divided into four mechanisms: metabolism, circulation, ventilation and sweating. The metabolism is modified by the shivering (which depends on the body temperature) and the physical activity; the circulation depends on the body gas concentrations, the temperature and the metabolism; the ventilation depends on the gas concentrations; the sweating depends on the temperature. Implicit methods were used to solve the differential equations. The discretization of the partial differential equations was obtained applying the finite volume method. Comparisons with experimental works found in literature show that the model is suitable to represent the exposure to cold and warm ambients, to low amounts of oxygen, to carbon dioxide, and physical activity. Other results of the developed model show that decompression accidents become more severe when associated to low ambient temperatures, because of the increase in the O2 consumption by shivering. The shivering also increases the danger of a CO2 intoxication, due to the increase of its production. The model showed as well the capacity to represent the several interactions between the thermal and respiratory systems, as the decrease of the body temperature because of the increase in the ventilation (which depends on the O2 and CO2 concentrations), or the decrease of the O2 and CO2 partial pressures in the more extreme segments, consequence of the temperature effect on their blood transport capacity.

O modelo do sistema térmico do corpo humano consegue representar as respostas térmicas e fisiológicas do corpo a diferentes condições ambientais. Diversos modelos foram propostos por pesquisadores durante algumas décadas. E mesmo os modelos mais utilizados e de pesquisadores conceituados não são robustos o suficiente para apresentar boas respostas para condições ambientais extremas. No presente trabalho, foram introduzidas melhorias no modelo disponível para que este possa melhor representar as reações do corpo em condições de climas tanto rigorosas quanto amenas. Dentre as principais modificações implementadas estão o detalhamento dos membros superiores do corpo, aplicação do efeito q10 e inclusão do modelo de duração da termogênese ativa. Deve-se ressaltar que o modelo é aplicável tanto para climas frios ou quentes. As melhorias devido às modificações aplicadas foram mais notáveis em condições de ambientes frios. As temperaturas das extremidades dos membros superiores tendem a se aproximar da temperatura ambiente. Esse comportamento térmico do corpo também é observado através dos dados experimentais disponíveis na literatura. / The thermal system model of human body is capable to estimate physical and physiological response of body at different environmental conditions. Several models were proposed by some researchers over the last 80 years. Most models are not robust, despite at current developments and studies in the area. In the present work, improvements were applied in the available model, this upgrade allows the human thermal system model respond better at both environmental conditions rigorous and moderate. Detailing the upper limbs vascular system, finger representation, q10 effect on metabolism rate and shivering endurance are among the major changes. The model works well for both environmental conditions, hot and cold. The difference between the proposed model and the available one is most notable at cold environmental condition. The temperature of fingers and hands tend to approach the environment temperature. This thermal behavior of human body is also observable in the experimental data of literature.

O modelo do sistema térmico do corpo humano consegue representar as respostas térmicas e fisiológicas do corpo a diferentes condições ambientais. Diversos modelos foram propostos por pesquisadores durante algumas décadas. E mesmo os modelos mais utilizados e de pesquisadores conceituados não são robustos o suficiente para apresentar boas respostas para condições ambientais extremas. No presente trabalho, foram introduzidas melhorias no modelo disponível para que este possa melhor representar as reações do corpo em condições de climas tanto rigorosas quanto amenas. Dentre as principais modificações implementadas estão o detalhamento dos membros superiores do corpo, aplicação do efeito q10 e inclusão do modelo de duração da termogênese ativa. Deve-se ressaltar que o modelo é aplicável tanto para climas frios ou quentes. As melhorias devido às modificações aplicadas foram mais notáveis em condições de ambientes frios. As temperaturas das extremidades dos membros superiores tendem a se aproximar da temperatura ambiente. Esse comportamento térmico do corpo também é observado através dos dados experimentais disponíveis na literatura. / The thermal system model of human body is capable to estimate physical and physiological response of body at different environmental conditions. Several models were proposed by some researchers over the last 80 years. Most models are not robust, despite at current developments and studies in the area. In the present work, improvements were applied in the available model, this upgrade allows the human thermal system model respond better at both environmental conditions rigorous and moderate. Detailing the upper limbs vascular system, finger representation, q10 effect on metabolism rate and shivering endurance are among the major changes. The model works well for both environmental conditions, hot and cold. The difference between the proposed model and the available one is most notable at cold environmental condition. The temperature of fingers and hands tend to approach the environment temperature. This thermal behavior of human body is also observable in the experimental data of literature.

No description available.

Presented in this thesis are the following theoretical investigations carried out on the non-invasive microwave hyperthermia of malignant tumours in the human body: Fundamental concepts of electromagnetic wave propagation through a biomass and its interaction with it, are discussed. Various types of applicators used for producing hyperthermia in a biomass, are also discussed. Propagation of a uniform plane electromagnetic wave through a human body is investigated for the general case of oblique incidence. Various models used for the human body have been discussed and the planar multilayer model has been chosen for this study. Reflection and transmission coefficients for both the parallel and perpendicular linear polarisations of the wave, have been determined. For normal incidence, power transfer ratio at the muscle has been defined and calculated at 433, 915 and 2450 MHz (ISM frequencies). Efects of skin thickness and also of fat thickness, on the power transfer ratio at muscle, have been studied. Effects of the thickness and dielectric constant of a bolus, and also of the dielectric constant of an initial layer, on the power transfer ratio, have been studied and their optimum values obtained at the ISM frequencies. For microwave hyperthermia, 915 MHz is recommended as the frequency of operation. Steady-state solution of the bioheat transfer equation has been obtained, assuming the biomass to be a semi-infinite homogeneous medium. Effects of various physical parameters on the temperature profile in the biomass, have been studied. Also studied is the effect of the surface temperature on the magnitude, location and the width of the temperature peak attained in the biomass. A method to determine the microwave power and the surface temperature required to produce a prescribed temperature profile in the biomass, has been developed. The transient-state solution of the bioheat transfer equation has been obtained to study the building up of the temperature profile. Procedures for the design of an open-ended rectangular metal waveguide applicator and for estimating the total microwave power requirement to produce hyperthermia in the human body, have been developed. Performance of the applicators employing linear as well as planar arrays of open-ended rectangular metal waveguide antennas, has also been studied. In order to reduce the overall physical size of the applicators, filling up of the feed waveguide with a high dielectric constant but low loss material is suggested. A simple method of obtaining the elements of the array by partitioning a large aperture by using metal walls has been adopted. Calculation of the total microwave power required by various applicators for producing hyperthermia at various depths in a biomas, have been made and a comparison of the performance of various applicators, has been presented.