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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
61

MR-guided thermotherapies of mobile organs : advances in real time correction of motion and MR-thermometry / Thermothérapies guidées par IRM sur organes mobiles : avancées sur la correction en temps réel du mouvement et de la thermométrie

Roujol, Sébastien 25 May 2011 (has links)
L'ablation des tissus par hyperthermie locale guidée par IRM est une technique prometteuse pour le traitement du cancer et des arythmies cardiaques. L'IRM permet d'extraire en temps réel des informations anatomiques et thermiques des tissus. Cette thèse a pour objectif d'améliorer et d'étendre la méthodologie existante pour des interventions sur des organes mobiles comme le rein, le foie et le coeur. La première partie a été consacrée à l'introduction de l'imagerie rapide (jusqu'à 10-15 Hz) pour le guidage de l'intervention par IRM en temps réel. L'utilisation de cartes graphiques (GPGPU) a permis une accélération des calculs afin de satisfaire la contrainte de temps réel. Une précision, de l'ordre de 1°C dans les organes abdominaux et de 2-3°C dans le coeur, a été obtenue. Basé sur ces avancées, de nouveaux développements méthodologiques ont été proposés dans une seconde partie de cette thèse. L'estimation du mouvement basée sur une approche variationnelle a été améliorée pour gérer la présence de structures non persistantes et de fortes variations d'intensité dans les images. Un critère pour évaluer la qualité du mouvement estimé a été proposé et utilisé pour auto-calibrer notre algorithme d'estimation du mouvement. La méthode de correction des artefacts de thermométrie liés au mouvement, jusqu'ici restreinte aux mouvements périodiques, a été étendue à la gestion de mouvements spontanés. Enfin, un nouveau filtre temporel a été développé pour la réduction du bruit sur les cartographies de température. La procédure interventionnelle apparaît maintenant suffisamment mature pour le traitement des organes abdominaux et pour le transfert vers la clinique. Concernant le traitement des arythmies cardiaques, les méthodes ont été évaluées sur des sujets sains et dans le ventricule gauche. Par conséquent, la faisabilité de l'intervention dans les oreillettes mais aussi en présence d'arythmie devra être abordée. / MR-guided thermal ablation is a promising technique for the treatment of cancer and atrial fibrillation. MRI provides both anatomical and temperature information. The objective of this thesis is to extend and improve existing techniques for such interventions in mobile organs such as the kidney, the liver and the heart. A first part of this work focuses on the use of fast MRI (up to 10-15 Hz) for guiding the intervention in real time. This study demonstrated the potential of GPGPU programming as a solution to guarantee the real time condition for both MR-reconstruction and MR-thermometry. A precision in the range of 1°C and 2-3°C was obtained in abdominal organs and in the heart, respectively. Based on these advances, new methodological developments have been carried out in a second part of this thesis. New variational approaches have proposed to address the problem of motion estimation in presence of structures appearing transient and high intensity variations in images. A novel quality criterion to assess the motion estimation is proposed and used to autocalibrate our motion estimation algorithm. The correction of motion related magnetic susceptibility variation was extended to treat the special case of spontaneous motion. Finally, a novel temporal filter is proposed to reduce the noise of MR-thermometry measurements while controlling the bias introduced by the filtering process. As a conclusion, all main obstacles for MR-guided HIFU-ablation of abdominal organs have been addressed in in-vivo and ex-vivo studies, therefore clinical studies will now be realized. However, although promising results have been obtained for MR-guided RF-ablation in the heart, its feasibility in the atrium and in presence of arrhythmia still remains to be investigated.
62

Eficiência do uso da água e produtividade de biomassa do milheto (Pennisetum glaucum (L.) R. Br.) sob diferentes níveis de reposição hídrica / Efficiency of water use and biomass productivity of millet (Pennisetum glaucum (L.) R. Br.) Under different levels of water replenishment

Almeida, Ailson Maciel de 03 July 2017 (has links)
O crescimento da população mundial associado ao aumento da competição pelos recursos hídricos, desafiam a humanidade a buscar alternativas para solucionar os problemas de abastecimento de água e oferta de alimentos. Isso exige de pesquisadores e institutos de pesquisa soluções para aumentar a eficiência na produção de alimentos e na eficiência no uso dos recursos hídricos. O milheto (Pennisetum glaucum (L.) R. Br.) pode ser uma alternativa viável para a produção de biomassa e forragem com maior eficiência no uso da água. Deste modo, levanta-se a hipótese de que a diminuição na oferta de água aumenta a produtividade da água na cultura; o objetivo deste trabalho foi investigar o incremento de produtividade da água da cultura, associado à diminuição na oferta de água, bem como, o padrão de resposta termal da cultura em função do déficit hídrico. O estudo foi conduzido em um ambiente protegido na área de pesquisa do Departamento de Engenharia de Biossistemas da Escola Superior de Agricultura -Luiz de Queiroz? entre novembro de 2016 e janeiro de 2017. A variedade utilizada neste trabalho foi a BRS-1501, desenvolvida pela EMBRAPA, o delineamento experimental adotado foi o de blocos casualizados com quatro blocos e quatro níveis de reposição hídrica, sendo eles: (L40, L70, L100 e L130).O nível de reposição hídrica de referência (L100) foi mantido ao longo do experimento próximo à capacidade de campo (θcc). A unidade experimental considerada foi de uma caixa com uma área de 0,261 m2, com um volume de solo aproximado de 100 litros contendo seis plantas. Foram avaliados o potencial de água na folha, a temperatura foliar, para o cálculo do CWSI, e, na colheita, foi medido o índice de área foliar (IAF), e a produção de biomassa da parte aérea, para estimativa de produtividade de biomassa da parte aérea, e de água para a cultura. Os tratamentos foram aplicados aos 15 dias após a semeadura (DAS) e se seguiram até a colheita. As variáveis avaliadas apresentaram relações significativas com os tratamentos que foram impostos. O CWSI calculado para a cultura foi representativo e apresentou boa correlação com o potencial de água na folha no modelo linear. O índice de área foliar oscilou entre 5,9m2 m-2 e 9,4 m2 m-2, em valores médios, entre os tratamentos de irrigação. O valor máximo de produtividade de biomassa seca da parte aérea se deu no tratamento L130, com valor médio de 12,1 Mg ha-1, e o menor valor de produtividade de biomassa se deu no tratamento L40, com valor médio de 5,15 Mg ha-1. Os valores médios de produtividade de água foram expressivos para o tratamento de reposição L40, com valor aproximado de 9,1 kg m-3 de biomassa produzida, evidenciando a grande eficiência no uso da água pela cultura. / The growth of the world population associated with increased competition for water resources challenges humanity to seek alternatives to solve the problems of water supply and food supply. This requires researchers and research institutes to increase their efficiency in food production and the efficiency of their use of water resources. The millet (Pennisetum glaucum (L.) R. Br.) can be a viable alternative for the production of biomass and forage with greater efficiency in the use of water. Thus, it is hypothesized that the decrease in water supply increases the productivity of water in the crop; the objective of this work was to investigate the increase of crop water productivity, associated with the decrease in water supply, as well as the thermal response pattern of the crop as a function of the water deficit. The study was conducted in a protected environment in the research area of the Department of Biosystems Engineering of the \"Luiz de Queiroz\" School of Agriculture between November 2016 and January 2017. The variety used in this work was BRS-1501, developed by EMBRAPA, the experimental design was a randomized block design with four blocks and four water replenishment levels: (L40, L70, L100 and L130). The reference water replenishment level (L100) was maintained throughout the experiment close to the field capacity (θcc).The experimental unit considered was a box with 0.261 m2 containing six plants. Leaf water potential, leaf temperature, for the CWSI calculation, leaf area index (LAI) and leaf biomass production were estimated for estimating biomass productivity of aerial part, and of water for the culture. The treatments were applied at 15 days after seeding (DAS) and were followed until harvest. The evaluated variables presented significant relationships with the treatments that were imposed. The CWSI calculated for the crop was representative and showed good correlation with the leaf water potential in the linear model. The leaf area index ranged from 5.9 m2 m-2 to 9.4 m2 m-2, in average values, between irrigation treatments. The maximum productivity of dry biomass of aerial part was given in the treatment L130, with average value of 12.1 Mg ha-1, and the lowest value of biomass productivity occurred in the treatment L40, with an average value of 5,15 Mg ha-1. The mean values of water productivity were significant for the L40 replacement treatment, with an approximate value of 9.1 kg m-3 of biomass produced, evidencing the great efficiency in the use of crop water.
63

Ensino de calorimetria com ênfase no desenvolvimento da habilidade de leitura e interpretação de gráficos

Schneider, Gabriel Schabbach January 2016 (has links)
Neste trabalho é apresentada uma proposta para o ensino de termometria e calorimetria, em nível de ensino médio, que enfatiza a habilidade de leitura e interpretação de gráficos. A motivação do trabalho é o crescente aumento da importância, no cenário nacional, do Exame Nacional do Ensino Médio (ENEM) exigindo a referida habilidade em parcela significativa das questões. A fundamentação teórica está baseada na Teoria da Aprendizagem de David Ausubel, tanto no que diz respeito à concepção e elaboração do material instrucional, quanto à sua aplicação em sala de aula. O módulo didático, perfazendo um total de 20 horas aula, é composto por um conjunto de aulas expositivo-dialogadas, aulas práticas, listas de exercícios, que partem de exercícios elementares até exercícios de concursos de vestibular, exercícios associados à visualização de vídeos, correção de atividades com a projeção de respostas erradas inspiradas no Peer Instruction e um texto produzido especialmente para o produto educacional, constituindo-se este conjunto no produto educacional do mestrado. Quanto à habilidade de leitura e interpretação de gráficos, adotou-se a classificação de Curcio em três níveis: “ler os dados, ler entre os dados e ler além dos dados”. O módulo didático foi aplicado no Colégio Concórdia de Porto Alegre em uma turma de 37 alunos do segundo ano do Ensino Médio. Para avaliar os alunos na leitura e interpretação de gráficos foi produzido um teste de conhecimentos prévios e conhecimentos adquiridos, com quinze questões que envolvem a leitura e interpretação de gráficos em diferentes níveis conforme a classificação de Curcio. O teste de opinião aplicado para avaliar a percepção dos alunos em relação ao desenvolvimento da proposta, de um modo geral, foi favorável à proposta. / This dissertation presents a proposal for teaching thermometry and calorimetry at high school level, which emphasizes graphs reading and interpreting skills. The motivation behind this study is the increasing importance, on the Brazilian national scene, of the National Secondary Education Exam (ENEM), requiring these skills in a significant portion of the questions. The theoretical foundation is the Meaningful Learning Theory by David Ausubel, regarding the design and preparation of instructional material for its use in the classroom. The teaching module, comprising a total of 20 class hours, consists of a set of expository-dialogued classes, practical classes, exercises, starting from elementary exercises to university entrance exams questions, exercises associated with video watching, tasks correction with the projection of wrong answers based on Peer Instruction and a text produced especially for the educational product, constituting this set the educational product for a master degree program. As for graphs reading and interpreting skills, Curcio´s classification has been adopted on three levels: "reading the data, reading between the data and reading beyond the data". The teaching module was applied to a class of 37 students in the second year of high school at Concordia School in the City of Porto Alegre. In order to assess students about graphs reading and interpreting, it was produced a pretest with fifteen questions at different levels according to Curcio´s classification. This test was applied before the didactic proposal for two main reasons: to detect previous knowledge of the students and to evaluate their learning improvement after the implementation of the proposal, using the same test as a posttest. At the end of the teaching module, a test was applied to assess the acquired knowledge of thermometry and calorimetry. The opinion test used to assess the students' perception concerning the proposal, in general, was favorable to the proposal.
64

Intération du modèle du signal IRM pour la correction du mouvement et segmentation d'images automatisée : application à la thermométrie cardiaque / MRI signal model integration for the motion correction and automated images segmentation : Application to cardiac thermometry

Emilien, Aurelie 15 December 2014 (has links)
Les travaux présentés dans ce manuscrit s’inscrivent dans un projet de thermométrie cardiaque par IRM. L’objectif de cette approche est de monitorer en temps réel le traitement des arythmies cardiaques par ablation thermique. Dans la chaine de traitement utilisée, des méthodes de recalage d’images doivent être implémentées afin d’assurer un suivi exploitable de l’ablation. En effet, les mouvements des différents organes localisés dans la (les) coupe(s) d’imagerie ont un impact sur la précision de la thermométrie IRM. Les méthodes d’estimation de mouvement doivent cependant être robustes aux différents artefacts (faible SNR, flux sanguin dans les cavités cardiaques, etc.) et utilisables en pseudo temps réel (10 images/seconde). Les travaux présentés dans ce manuscrit se concentrent sur la robustesse des méthodes de recalage d’images. Tout d’abord, le bruit inhérent aux images IRM a été intégré à l’estimation de mouvement. Ceci permet de pondérer localement les voxels de l’image dans le calcul du déplacement. Ensuite, une annulation numérique du signal chaotique du sang à l’intérieur du ventricule gauche est proposée via une segmentation semi-automatique de celuici à base de modèle déformable. Un nouveau terme, issu de la probabilité d’appartenir à ce ventricule, a été ajouté dans l’algorithme de contour actif. Les méthodes proposées apportent une amélioration de la qualité de l’estimation du mouvement. Elles sont adaptées à la chaine de traitement de thermométrie afin de les rendre automatiques dans la phase d’ablation thermique de la procédure. De plus, ces méthodes répondent aux contraintes de temps réel de la thermométrie IRM / The works presented in the manuscript are incorporated within the framework of cardiac MR thermometry. The aim of this approach is to monitor in real time the treatment of arrhy²thmias by thermal ablation. In the pipeline used in thermometry, image registration methods have to be inserted to unsure a reliable monitoring of the treatment. Indeed, motions of the different organs present in the acquisition slices have an impact on the accuracy of the MR thermometry. Furthermore, image registration has to be robust to artefacts (low SNR, blood flow in the heart cavities…) and has to be used in real time (10 images/second). The works presented in this manuscript focuses on the robustness of the image registration methods. First, the MR images inherent noise is integrated to the motion estimation. It enables the local weighting of the image’s voxels in the computing of the displacement. Then, a numerical cancelation of the chaotic blood flow signal within the left ventricle through a semi-automatic segmentation is proposed. A new term based on the probability to belong to this ventricle is added to the active contour algorithm. The proposed methods improved the quality of the motion estimation. They are adapted to the thermometry pipeline to make them automatic in the thermal ablation phase of the procedure. They are also compatible with the real-time aspect of MR thermometry.
65

Thermal Modeling of Shape Memory Alloy Wire Actuators for Automotive Applications

Ma, Huilong January 2010 (has links)
Shape Memory Alloy is an amazing material, which can “remember” and return to its original shape when heated due to its temperature dependent phase transformation. Shape Memory Alloy wire has significant potential for application in the automobile industry due to its high ratio of energy / weight and silent actuation. However, a dependable method to measure the operating temperature of SMA wire and a reliable heat transfer model to characterize the dynamics of the SMA wire limit its widespread use in the automobile industry. This thesis presents a detailed description of the work performed to develop a reliable method for determining surface temperature of current carrying SMA wires and the development of a heat transfer correlation for natural convection cooling of heated SMA wires. The major findings of the research are as follows: When a spot welded thermocouple measures the temperature of a current carrying SMA wire, there is a “spurious voltage” ΔV added to the thermo electro-motive force (EMF) of the thermocouple as a result of a voltage drop across the two points of contact that the thermocouple wires make with the SMA wire. This leads to an erroneous temperature reading that can be higher or lower than the actual temperature depending on the direction of current flow. When the carrying current is reversed in direction, the “spurious voltage” becomes –ΔV allowing a correct temperature reading to be obtained by averaging the readings based on opposed current flow. A two-step spot welding procedure for attaching thermocouples to SMA wire can eliminate the influence of the “spurious voltage” in the temperature reading. By spot welding the thermocouple wires onto the SMA wire one by one, the thermocouple lead offset is eliminated and the thermocouple provides an accurate point source reading. Infrared thermal imaging can be a good supplement in the experiment to monitor errors in temperature readings from thermocouples. Due to the curvature of the SMA wire, the temperatures of the locations on the SMA wire that are the closest to the infrared camera represent the temperature of the SMA wire. So a line analysis across the SMA wire on the software “ThermaCAM” is required to determine the temperature of the SMA wire by infrared thermal imaging and the highest temperature on the line is the temperature of the SMA wire. A new natural convective heat transfer correlation comprising the inclination angle φ is developed based on experimental results, which can be used to predict the temperature of a SMA wire given its diameter and inclination angle. The comparisons show that the new correlation agrees with existing correlations in a vertical orientation and for small Rayleigh numbers (0.001 < RaD < 0.05) in the horizontal orientation. The correlation developed in this work for horizontal orientation tends to overestimate values of Nusselt numbers as predicted in other correlations when the Rayleigh number is high (0.05 < RaD < 0.6). It is speculated that this overestimation can be attributed to a temperature distortion associated with thermocouple measurement at or near ambient pressure conditions.
66

Development of MR Thermometry Strategies for Hyperthermia of Extremity and Breast Tumors

Wyatt, Cory Robert January 2010 (has links)
<p>Numerous studies have shown that the combination of radiation therapy and hyperthermia, when delivered at moderate temperatures (40°-45°C) for sustained times (30-90 minutes), can help to provide palliative relief and augment tumor response, local control, and survival. However, the dependence of treatment success on achieved temperature highlights the need for accurate thermal dosimetry, so that the prescribed thermal dose can be delivered to the tumor. This can be achieved noninvasively with MR thermometry. However, there are many challenges to performing MR thermometry in the breast, where hyperthermia of locally advanced breast cancer can provide a benefit. These include magnetic field system drift, fatty tissue, and breathing motion.</p> <p>The purpose of this research was to develop a system for the hyperthermia treatment of LABC while performing MR thermometry. A hardware system was developed for performing the hyperthermia treatment within the MR bore. Methods were developed to correct for magnetic field system drift and to correct for breath hold artifacts in MR thermometry of the tumor using measurement of field changes in fat references. Lastly, techniques were developed for measuring temperature in the fatty tissue using multi-echo fat water separation methods, reducing the error of performing MR thermometry in such tissues. All of these methods were characterized with phantom and in vivo experiments in a 1.5T MR system. </p> <p>The results of this research can provide the means for successful hyperthermia treatment of LABC with MR thermometry. With this thermometry, accurate thermal doses can be obtained, potentially providing improved outcomes. However, these results are not only applicable in the breast, but can also be used for improved MR thermometry in other areas of the body, such as the extremities or abdomen.</p> / Dissertation
67

Combustor Exhaust Temperature Nonuniformity Sensing Using Diode Laser Absorption

Palaghita, Tudor I. 12 February 2007 (has links)
This thesis describes the development of a sensing technique for temperature nonuniformity along the line of sight through combustion exhaust, geared for gas turbine applications. Tunable diode laser absorption spectroscopy is used to measure three absorption lines and compute a variable to characterize the level of temperature nonuniformity along the laser path. Nonuniformity information is obtained from one line of sight sensor because the absorption has a nonlinear dependence on temperature. This dependence is analyzed to determine the behaviour, shape, and response of absorption lines measured through mediums with nonuniform temperature profiles. Based on this analysis a new line selection process for nonuniformity sensing is developed. A sensor for temperature nonuniformity is proposed and demonstrated through computer simulations and experiments in the exhaust of a laboratory-scale combustor. The nonuniformity variable, U, is shown to monotonically track the level of temperature nonuniformity along the laser path. The capabilities of this sensing technique are determined based on a comprehensive analysis of errors and their effect on sensor performance. Methods to mitigate these errors are described, and the overall sensor capability is determined based on the characteristics of state of the art diode laser and absorption sensor technology. Such a sensor is capable of measuring minimum temperature deviations of 17% or more, which is well within the needed capabilities for industrial applications. Furthermore, the results and knowledge presented in this thesis apply to other absorption based sensing techniques.
68

Hyperthermia Mediated Drug Delivery using Thermosensitive Liposomes and MRI-Controlled Focused Ultrasound

Staruch, Robert Michael 14 January 2014 (has links)
The clinical efficacy of chemotherapy in solid tumours is limited by systemic toxicity and the inability to deliver a cytotoxic concentration of anticancer drugs to all tumour cells. Temperature sensitive drug carriers provide a mechanism for triggering the rapid release of chemotherapeutic agents in a targeted region. Thermally mediated drug release also leverages the ability of hyperthermia to increase tumour blood flow, vessel permeability, and drug cytotoxicity. Drug release from thermosensitive liposome drug carriers in the tumour vasculature serves as a continuous intravascular infusion of free drug originating at the tumour site. However, localized drug release requires precise heating to improve drug delivery and efficacy in tumours while minimizing drug exposure in normal tissue. Focused ultrasound can noninvasively heat millimeter-sized regions deep within the body, and can be combined with MR thermometry for precise temperature control. This thesis describes the development of strategies to achieve localized hyperthermia using MRI-controlled focused ultrasound, for the purpose of image-guided heat-triggered drug release from thermosensitive drug carriers. First, a preclinical MRI-controlled focused ultrasound system was developed as a platform for studies of controlled hyperthermia and drug delivery in rabbits. The feasibility of using ultrasound hyperthermia to achieve localized doxorubicin release from thermosensitive liposomes was demonstrated in normal rabbit muscle. Second, strategies were described for using MR thermometry to control ultrasound heating at a muscle-bone interface based on MR temperature measurements in adjacent soft tissue, demonstrating localized drug delivery in adjacent muscle and bone marrow. Third, fluorescence microscopy was employed to demonstrate that increased overall drug accumulation in rabbit VX2 tumours corresponds to high levels of bioavailable drug reaching their active site in the nuclei of tumour cells. The results of this thesis demonstrate that image-guided drug delivery using thermosensitive liposomes and MRI-controlled focused ultrasound hyperthermia can be used to noninvasively achieve precisely localized drug deposition in soft tissue, at bone interfaces, and in solid tumours. Clinical application of this work could provide a noninvasive means of enhancing chemotherapy in a variety of solid tumours.
69

Thermal Modeling of Shape Memory Alloy Wire Actuators for Automotive Applications

Ma, Huilong January 2010 (has links)
Shape Memory Alloy is an amazing material, which can “remember” and return to its original shape when heated due to its temperature dependent phase transformation. Shape Memory Alloy wire has significant potential for application in the automobile industry due to its high ratio of energy / weight and silent actuation. However, a dependable method to measure the operating temperature of SMA wire and a reliable heat transfer model to characterize the dynamics of the SMA wire limit its widespread use in the automobile industry. This thesis presents a detailed description of the work performed to develop a reliable method for determining surface temperature of current carrying SMA wires and the development of a heat transfer correlation for natural convection cooling of heated SMA wires. The major findings of the research are as follows: When a spot welded thermocouple measures the temperature of a current carrying SMA wire, there is a “spurious voltage” ΔV added to the thermo electro-motive force (EMF) of the thermocouple as a result of a voltage drop across the two points of contact that the thermocouple wires make with the SMA wire. This leads to an erroneous temperature reading that can be higher or lower than the actual temperature depending on the direction of current flow. When the carrying current is reversed in direction, the “spurious voltage” becomes –ΔV allowing a correct temperature reading to be obtained by averaging the readings based on opposed current flow. A two-step spot welding procedure for attaching thermocouples to SMA wire can eliminate the influence of the “spurious voltage” in the temperature reading. By spot welding the thermocouple wires onto the SMA wire one by one, the thermocouple lead offset is eliminated and the thermocouple provides an accurate point source reading. Infrared thermal imaging can be a good supplement in the experiment to monitor errors in temperature readings from thermocouples. Due to the curvature of the SMA wire, the temperatures of the locations on the SMA wire that are the closest to the infrared camera represent the temperature of the SMA wire. So a line analysis across the SMA wire on the software “ThermaCAM” is required to determine the temperature of the SMA wire by infrared thermal imaging and the highest temperature on the line is the temperature of the SMA wire. A new natural convective heat transfer correlation comprising the inclination angle φ is developed based on experimental results, which can be used to predict the temperature of a SMA wire given its diameter and inclination angle. The comparisons show that the new correlation agrees with existing correlations in a vertical orientation and for small Rayleigh numbers (0.001 < RaD < 0.05) in the horizontal orientation. The correlation developed in this work for horizontal orientation tends to overestimate values of Nusselt numbers as predicted in other correlations when the Rayleigh number is high (0.05 < RaD < 0.6). It is speculated that this overestimation can be attributed to a temperature distortion associated with thermocouple measurement at or near ambient pressure conditions.
70

Hyperthermia Mediated Drug Delivery using Thermosensitive Liposomes and MRI-Controlled Focused Ultrasound

Staruch, Robert Michael 14 January 2014 (has links)
The clinical efficacy of chemotherapy in solid tumours is limited by systemic toxicity and the inability to deliver a cytotoxic concentration of anticancer drugs to all tumour cells. Temperature sensitive drug carriers provide a mechanism for triggering the rapid release of chemotherapeutic agents in a targeted region. Thermally mediated drug release also leverages the ability of hyperthermia to increase tumour blood flow, vessel permeability, and drug cytotoxicity. Drug release from thermosensitive liposome drug carriers in the tumour vasculature serves as a continuous intravascular infusion of free drug originating at the tumour site. However, localized drug release requires precise heating to improve drug delivery and efficacy in tumours while minimizing drug exposure in normal tissue. Focused ultrasound can noninvasively heat millimeter-sized regions deep within the body, and can be combined with MR thermometry for precise temperature control. This thesis describes the development of strategies to achieve localized hyperthermia using MRI-controlled focused ultrasound, for the purpose of image-guided heat-triggered drug release from thermosensitive drug carriers. First, a preclinical MRI-controlled focused ultrasound system was developed as a platform for studies of controlled hyperthermia and drug delivery in rabbits. The feasibility of using ultrasound hyperthermia to achieve localized doxorubicin release from thermosensitive liposomes was demonstrated in normal rabbit muscle. Second, strategies were described for using MR thermometry to control ultrasound heating at a muscle-bone interface based on MR temperature measurements in adjacent soft tissue, demonstrating localized drug delivery in adjacent muscle and bone marrow. Third, fluorescence microscopy was employed to demonstrate that increased overall drug accumulation in rabbit VX2 tumours corresponds to high levels of bioavailable drug reaching their active site in the nuclei of tumour cells. The results of this thesis demonstrate that image-guided drug delivery using thermosensitive liposomes and MRI-controlled focused ultrasound hyperthermia can be used to noninvasively achieve precisely localized drug deposition in soft tissue, at bone interfaces, and in solid tumours. Clinical application of this work could provide a noninvasive means of enhancing chemotherapy in a variety of solid tumours.

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