The Thermoelectric Perfusion Probe is a completely electronic system that cyclically heats and cools tissue to measure blood perfusion. The probe produces the thermal event with a thermoelectric cooler and then measures the resulting heat flux and temperatures: the arterial temperature and the sensor temperature (the temperature between the heat flux gage and the skin). The Thermoelectric Perfusion Probe was validated and calibrated on a phantom tissue test stand, a system that simulates perfusion with known, controlled flow. With the new pressed sensor technology, a thermocouple sealed to a heat flux gage, the sensor temperature and the heat flux are simultaneously recorded. The pressed sensor tests validated the program used to predict perfusion for the Thermoelectric Perfusion Probe. This perfusion estimation program can determine the tissues perfusion regardless of how the thermal event is created (i.e. convective cooling, convective heating, conductive heating). Based on experimentation, the Thermoelectric Perfusion Probe displays good repeatability and sensitivity for continuously measuring perfusion. The sensitivity and repeatability of the Thermoelectric Perfusion Probe was proven when the perfusion estimates were compared to the perfusion estimates predicted by the Convective Perfusion Probe, a previously validated perfusion probe, and the CFD Flow Model, a computational model of the phantom tissue test stand. / Master of Science

<p>Radio-frequency (RF) lesioning is a method utilising high frequency currents for thermal coagulation of pathological tissue or signal pathways. The current is delivered from an electrode with a temperature sensor, permitting control of the current at a desired target temperature. In the brain RF-lesioning can e.g. be used for severe chronic pain and movement disorders such as Parkinson’s disease. This thesis focuses on modelling and simulation with the aim of gaining better understanding and predictability of the lesioning process in deep brain structures. The finite element method (FEM) together with experimental comparisons was used to study the effects of electrode dimensions, electrode target temperature, electric and thermal conductivity of the brain tissue, blood perfusion and cerebrospinal fluid (CSF) filled cysts. Equations for steady current, thermal transport and incompressible flow were used together with statistical factorial design and regression analysis for this purpose.</p><p>Increased target temperature, electrode tip length and electrode diameter increased the simulated lesion size, which is in accordance with experimental results. The influence of blood perfusion, modelled as an increase in thermal conductivity in non-coagulated tissue, gave smaller simulated lesions with increasing blood perfusion as heat was more efficiently conducted from the rim of the lesion. If no consideration was taken to the coagulation the lesion became larger with increased thermal conductivity instead, as the increase in conducted heat was compensated for through an increased power output in order to maintain the target temperature. Simulated lesions corresponded well to experimental in-vivo lesions.</p><p>The electric conductivity in a homogeneous surrounding had little impact on lesion development. However this was not valid for a heterogeneous surrounding. CSF-filled cysts have a much higher electric conductivity than brain tissue focussing the current to them if the electrode tip is in contact with both. Heating of CSF can also cause considerable convective flow and as a result a very efficient heat transfer. This affected simulated as well as experimental lesion sizes and shapes resulting in both very large lesions if sufficient power compared to the cysts size was supplied and very small lesions if the power was low, mitigating the heat over a large volume.</p><p>In conclusion especially blood perfusion and CSF can greatly affect the lesioning process and appear to be important to consider when planning surgical procedures. Hopefully this thesis will help improve knowledge about and predictability of clinical lesioning.</p>

Radio-frequency (RF) lesioning is a method utilising high frequency currents for thermal coagulation of pathological tissue or signal pathways. The current is delivered from an electrode with a temperature sensor, permitting control of the current at a desired target temperature. In the brain RF-lesioning can e.g. be used for severe chronic pain and movement disorders such as Parkinson’s disease. This thesis focuses on modelling and simulation with the aim of gaining better understanding and predictability of the lesioning process in deep brain structures. The finite element method (FEM) together with experimental comparisons was used to study the effects of electrode dimensions, electrode target temperature, electric and thermal conductivity of the brain tissue, blood perfusion and cerebrospinal fluid (CSF) filled cysts. Equations for steady current, thermal transport and incompressible flow were used together with statistical factorial design and regression analysis for this purpose. Increased target temperature, electrode tip length and electrode diameter increased the simulated lesion size, which is in accordance with experimental results. The influence of blood perfusion, modelled as an increase in thermal conductivity in non-coagulated tissue, gave smaller simulated lesions with increasing blood perfusion as heat was more efficiently conducted from the rim of the lesion. If no consideration was taken to the coagulation the lesion became larger with increased thermal conductivity instead, as the increase in conducted heat was compensated for through an increased power output in order to maintain the target temperature. Simulated lesions corresponded well to experimental in-vivo lesions. The electric conductivity in a homogeneous surrounding had little impact on lesion development. However this was not valid for a heterogeneous surrounding. CSF-filled cysts have a much higher electric conductivity than brain tissue focussing the current to them if the electrode tip is in contact with both. Heating of CSF can also cause considerable convective flow and as a result a very efficient heat transfer. This affected simulated as well as experimental lesion sizes and shapes resulting in both very large lesions if sufficient power compared to the cysts size was supplied and very small lesions if the power was low, mitigating the heat over a large volume. In conclusion especially blood perfusion and CSF can greatly affect the lesioning process and appear to be important to consider when planning surgical procedures. Hopefully this thesis will help improve knowledge about and predictability of clinical lesioning.

A new mathematical model has been developed along with a new parameter estimation routine using surface temperature and heat flux measurements to estimate blood perfusion and thermal resistance in living tissue. Dynamic thermal measurements collected at the surface of the sensor before and after imposing a dynamic thermal cooling event are used with the model to estimate the blood perfusion, thermal resistance and core temperature. The Green\'s function based analytical solution does not require calculation of the whole tissue temperature distribution, which was not the case for the previous models. The result from the new model was proved to have better and more consistent results than previous models. The new model was validated to solve one of the unsolved biomedical problems which is the ability of detecting burn severity. The method was tested with a phantom perfusion system. The results matched known blood perfusion and thermal resistance values. The method was also tested with burns on animal models. Inflammation effects associated with the burns were studied using a newly developed term called the Burn Factor. This correlated with the severity of imposed burns. This work consists of three journal papers. The first paper introduces the mathematical model and its validation with finite-difference solutions. The second paper validates the physical aspects of the usage of the model with thermal measurement in detecting simulated burned layers and the associated perfusion. The third paper demonstrates the ability of the model to use thermal measurements to detect different burn severity of an animal model and to study the healing process. / Ph. D.

This work focuses on the development of a system to noninvasively estimate blood perfusion using thermal methods. This is accomplished by the combination of a bioprobe, biothermal model, and parameter estimation techniques. The probe consists of a heat flux sensor and surface thermocouple placed in contact with tissue while the opposite side is cooled by jets of room temperature air. The biothermal model predicts the temperature and heat flux within tissue and probe based upon the input of blood perfusion and the thermal contact resistance between probe and tissue. Parameter estimation techniques are developed that use the model to simultaneously estimate blood perfusion and contact resistance based on experimental heat flux and/or temperature. A gradient based system minimizes a sum of squares error function based on either or both heat flux and temperature. This system is tested on human forearms and in controlled flow rate experiments using tissue phantoms. Blood perfusion estimates from the controlled experiments are positively correlated with experimental flow rate. Experimental measurements and statistical analysis show distinct variations in the heat flux signal and rises in perfusion estimates with increasing flow rate. This research validates the use of thermal and parameter estimation methods to develop a practical, noninvasive probe to clinically measure blood perfusion. / Master of Science

In adult vertebrates, cardiovascular regulation is accomplished by numerous systems with neural, hormonal and local components responsible for the majority of regulation. These regulatory components work in concert to maintain the essential function of blood perfusion to adult tissues. Given the essential nature of this function it is therefore surprising that the development of cardiovascular regulation during gestation is poorly understood. The majority of what is known is based on a single vertebrate model, the fetal lamb. The fetal lamb has been used in multiple studies due to the clear clinical applications and has been pivotal in understanding the onset of regulation in developing vertebrates. However, study on the fetal lamb is limited to the latter 40% of gestation and has the added complication of an in-utero developmental strategy. Therefore the primary focus of this dissertation was to characterize basic cardiovascular regulation in the chicken embryo to provided the needed information for it's use an alternative to the fetal lamb. Developing chicken embryos rely on both alpha and beta adrenergic tones to maintain normal heart rate and arterial blood pressure during incubation. However, on day 21, just prior to hatch, these animals lose both tones on arterial pressure suggesting the onset of adult regulation. Cholinergic tone, however, was absent throughout chicken development indicating that it must mature during the neonatal life. Adult cardiovascular reflexes become apparent late in chicken development with a clear baroreflex specifically operating initially on day. However, an adult response to changes in ambient gas tension was absent during incubation suggesting embryos possess unique regulatory systems that are absent in adult chickens. This mechanism is comprised entirely of adrenergic systems with no cholinergic action during change in ambient gas tension. Similar developmental patterns were determined in embryos of the desert tortoise suggesting fundamental differences between in-utero and ex-utero developing vertebrates.

No description available.

O processo de envelhecimento é acompanhado por um declínio nas funções cognitivas, principalmente, de funções fluidas ou de processamento. Essas diminuições são pelo menos, em parte, devido a alterações estruturais e funcionais do sistema nervoso central. Uma abordagem para estudar as mudanças funcionais é a medição da utilização metabólica regional da glicose, ou, alternativamente, um parâmetro físico correlacionado ao metabolismo cerebral e à atividade funcional local, como o fluxo sanguíneo cerebral (CBF). Neste contexto, em Imagens por Ressonância Magnética (IRM), a técnica de Marcação dos Spins Arteriais (ASL) surge como uma importante ferramenta não invasiva para análises perfusionais. Seu uso não só permite avaliar a perfusão sanguínea cerebral, gerando mapas quantitativos de CBF, mas também fornecer uma alternativa para estudar a conectividade funcional (FC), um parâmetro importante para descrição da topologia e funcionalidade cerebral. Sessenta e três indivíduos saudáveis, na faixa etária entre dezoito à setenta e dois anos, foram recrutados para participar deste estudo. Análises estatísticas mostram uma diminuição de CBF em várias regiões cerebrais, especialmente nos lobos frontal e temporal, que acompanham o processo de envelhecimento. As medidas de FC foram obtidas em análises por regiões de interesse e teoria de grafos; estas também demostraram uma diminuição, com o avanço da idade, em regiões presentes nos lobos frontal e temporal, mas também relataram um maior número de regiões prejudicadas no lobo parietal. Portanto, usando uma técnica de imagem não invasiva, foi possível observar déficits de CBF além de alterações de aspectos da organização funcional, oferecendo valores quantitativos que podem ajudar na melhor descrição dos efeitos do envelhecimento na hemodinâmica cerebral. / Aging process is accompanied by a decline in cognitive functions foremost comprise fluid or processing-based functions. These decreases are at least partly due to structural and functional deteriorating changes of the central nervous system. One approach to study these functional changes is the measurement of the regional metabolic utilization of glucose, or, alternatively, a physical quantity correlated to cerebral metabolism and local functional activity, such as the cerebral blood flow (CBF). In this context, Arterial spin labeling (ASL) emerges as a noninvasive Magnetic Resonance Imaging (MRI) perfusion technique. Its use not only allows assessing cerebral perfusion, by generating CBF values, but also can provide an alternative to study functional connectivity (FC), which is an important parameter that describes the brain topology and functionality. Sixty-three healthy subjects, from age eighteen to seventy-two years, were recruited to participate in this study. ASL-CBF maps showed a decrease in several brain regions, especially in frontal and temporal lobes that follows aging process. FC measures were assessed with regions of interest (ROI-to-ROI) and graph theory analysis, also showing a decrease in regions present in frontal and temporal lobes, and also more impaired regions in the parietal lobe. Therefore, using a noninvasive imaging technique it was possible to observe CBF deficits besides alteration in aspects on functional organization, offering quantitative values that can help to describe better the aging effects on cerebral hemodynamics.

O processo de envelhecimento é acompanhado por um declínio nas funções cognitivas, principalmente, de funções fluidas ou de processamento. Essas diminuições são pelo menos, em parte, devido a alterações estruturais e funcionais do sistema nervoso central. Uma abordagem para estudar as mudanças funcionais é a medição da utilização metabólica regional da glicose, ou, alternativamente, um parâmetro físico correlacionado ao metabolismo cerebral e à atividade funcional local, como o fluxo sanguíneo cerebral (CBF). Neste contexto, em Imagens por Ressonância Magnética (IRM), a técnica de Marcação dos Spins Arteriais (ASL) surge como uma importante ferramenta não invasiva para análises perfusionais. Seu uso não só permite avaliar a perfusão sanguínea cerebral, gerando mapas quantitativos de CBF, mas também fornecer uma alternativa para estudar a conectividade funcional (FC), um parâmetro importante para descrição da topologia e funcionalidade cerebral. Sessenta e três indivíduos saudáveis, na faixa etária entre dezoito à setenta e dois anos, foram recrutados para participar deste estudo. Análises estatísticas mostram uma diminuição de CBF em várias regiões cerebrais, especialmente nos lobos frontal e temporal, que acompanham o processo de envelhecimento. As medidas de FC foram obtidas em análises por regiões de interesse e teoria de grafos; estas também demostraram uma diminuição, com o avanço da idade, em regiões presentes nos lobos frontal e temporal, mas também relataram um maior número de regiões prejudicadas no lobo parietal. Portanto, usando uma técnica de imagem não invasiva, foi possível observar déficits de CBF além de alterações de aspectos da organização funcional, oferecendo valores quantitativos que podem ajudar na melhor descrição dos efeitos do envelhecimento na hemodinâmica cerebral. / Aging process is accompanied by a decline in cognitive functions foremost comprise fluid or processing-based functions. These decreases are at least partly due to structural and functional deteriorating changes of the central nervous system. One approach to study these functional changes is the measurement of the regional metabolic utilization of glucose, or, alternatively, a physical quantity correlated to cerebral metabolism and local functional activity, such as the cerebral blood flow (CBF). In this context, Arterial spin labeling (ASL) emerges as a noninvasive Magnetic Resonance Imaging (MRI) perfusion technique. Its use not only allows assessing cerebral perfusion, by generating CBF values, but also can provide an alternative to study functional connectivity (FC), which is an important parameter that describes the brain topology and functionality. Sixty-three healthy subjects, from age eighteen to seventy-two years, were recruited to participate in this study. ASL-CBF maps showed a decrease in several brain regions, especially in frontal and temporal lobes that follows aging process. FC measures were assessed with regions of interest (ROI-to-ROI) and graph theory analysis, also showing a decrease in regions present in frontal and temporal lobes, and also more impaired regions in the parietal lobe. Therefore, using a noninvasive imaging technique it was possible to observe CBF deficits besides alteration in aspects on functional organization, offering quantitative values that can help to describe better the aging effects on cerebral hemodynamics.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-02-13T18:50:27Z No. of bitstreams: 1 thiagodossantosribeiro.pdf: 1282702 bytes, checksum: 3d347e1f5b2c2d1d122a47e12f71fc48 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-02-15T13:49:43Z (GMT) No. of bitstreams: 1 thiagodossantosribeiro.pdf: 1282702 bytes, checksum: 3d347e1f5b2c2d1d122a47e12f71fc48 (MD5) / Made available in DSpace on 2017-02-15T13:49:43Z (GMT). No. of bitstreams: 1 thiagodossantosribeiro.pdf: 1282702 bytes, checksum: 3d347e1f5b2c2d1d122a47e12f71fc48 (MD5) Previous issue date: 2016-09-16 / Este trabalho tem como objetivo efetuar uma análise da sensibilidade da perfusão sanguínea e da condutividade térmica ao se simular processos de queimadura de pele devido a uma fonte de calor externa, considerando diferentes condições de contorno e utilizando o método dos elementos finitos (MEF) para discretizar a equação de Pennes. O modelo 2D aqui empregado considera um tecido biológico formado pelas camadas de epiderme, derme e subcutânea, e considera também funções não lineares para perfusão sanguínea e condutividade térmica. A hipótese não linear se explica pelo fato que para a perfusão sanguínea observa-se um aumento seguido de uma diminui¸ca˜o acima das temperaturas específicas resultantes de danos induzidos pelo aumento de temperatura nos capilares sanguíneos, e que a condutividade térmica varia linearmente com o aumento da temperatura. O sistema de equações diferenciais ordinárias não lineares oriundo da discretização via MEF é resolvido empregando-se o método de Euler implícito em conjunto com o método de Picard. Uma vez determinado a distribuição de temperatura, o modelo de Arrhenius será utilizado para calcular o dano térmico e classificar a queimadura quanto ao seu grau (ou seja, primeiro, segundo ou terceiro grau). / This paper aims at performing a sensitivity analysis of blood perfusion and thermal conductivity when simulating skin burning process due to an external heat source, considering different boundary conditions and using the finite element method (FEM) to discretize Pennes’s equation. The 2D model employed here considers a biological tissue formed by epidermis, dermis and subcutaneous layers, and also considers nonlinear functions for blood perfusion and thermal conductivity. The nonlinear assumption is explained by the fact that for the blood perfusion it is observed an increase followed by a decrease greater than the specific temperatures resulting from damage induced by temperature increase in blood capillaries, and also that the thermal conductivity varies linearly with temperature growth. The system of nonlinear ordinary differential equations arising from the discretization by FEM is solved by employing the implicit Euler method in conjunction with the method of Picard. Once the distribution of temperature is determined, the Arrhenius model is used to calculate the thermal damage and classify the burn degree (i.e., first, second or third degree).