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Bibliography: p. 185-195. / xxii, 195 p. : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Two rigorous dose calculation methods have been devised to address the deficiencies of currently available dose calculation algorithms. The 1st method incorporates Fermi-Eyges mutiple scattering theory, the 2nd method developed is the Super-Monte Carlo method. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physics and Mathematical Physics, 1996?

Thesis (Ph.D.)--University of Adelaide, Dept. of Physics and Mathematical Physics, 2000. / Bibliography: leaves 241-250.

Thesis (M.Sc.-Res.)--University of Wollongong, 2008. / Typescript. Includes bibliographical references: page 88-96.

Thesis (M.A.)--University of Chicago, 1937. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M. Sc.)--Carleton University, 2001. / Includes bibliographical references (p. 108-116). Also available in electronic format on the Internet.

Thesis (M.A.)--University of Chicago, 1937. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Dans mon travail de thèse, différentes techniques IRM, certaines nouvellement introduites dans la littérature, ont été implémentées et testées, essentiellement sur le rongeur à haut champ magnétique. Les applications abordées couvrent un large spectre de pathologies dont l'importance en termes de santé publique n'est plus à démontrer : cancer, fibrose hépatique, maladie d'Alzheimer, sclérose en plaque...Ces examens pourraient être utilisés à différents stades de la prise en charge clinique : détection, caractérisation, thérapie, suivi post traitement. En ce qui concerne les applications diagnostiques (chapitres 2 et 3), l'élastographie par IRM est réalisée pour la première fois à 7T. La résolution isotrope atteint 300μm dans les cas les plus favorables et les fréquences accessibles couvrent le spectre 100-1000Hz. Le potentiel de la technique est évalué sur des modèles animaux de différentes pathologies : stéato-hépatite non induite par la consommation d'alcool, maladie d'Alzheimer, sclérose en plaque. Dans le foie, nos résultats montrent que les données d'élastographie sont sensibles à l'activation des cellules produisant le collagène responsable de la fibrose hépatique avant l'apparition de celle-ci. Cela permet chez l'animal de distinguer la stéatose simple (accumulation de graisse) de la stéato-hépatite non alcoolique. Dans le cerveau, les pathologies affectant la myéline résultent en une modification significative des paramètres viscoélastiques des structures de la substance blanche telles que le corps calleux. Ces résultats, s'ils sont confirmés chez les patients, pourraient fournir des nouveaux contrastes aux médecins pour détecter, grader et évaluer la réponse à un traitement pour les pathologies concernées. Dans une approche plus prospective, l'intérêt d'une mesure des paramètres viscoélastiques à plusieurs fréquences est démontré théoriquement et expérimentalement par élastographie IRM multifréquences et élastographie ultrasonore transitoire SSI, deux techniques indépendantes. Les tissus mous sont très dispersifs. L'origine de cette dispersion est l'atténuation, elle-même très probablement induite par la diffusion des ondes sur des structures dures aux échelles inférieures à notre résolution d'imagerie (~1mm). La dépendance des courbes de dispersion mesurées à l'échelle macroscopique vis-à-vis de modifications de composition et de structure à des échelles bien inférieures à la longueur d'onde et à la résolution d'imagerie est démontrée ici. Fort de ce résultat, il est possible de porter un nouveau regard sur les techniques d'élastographie, véritables outils de caractérisation rhéologique in vivo, qui peuvent être utilisées pour suivre des phénomènes biologiques intervenant aux échelles microscopiques donc invisibles par imagerie anatomique directe. Cette approche pourrait apporter beaucoup en routine clinique dans les années à venir, par exemple pour suivre les effets des évolutions du réseau vasculaire sur l'élasticité effective et sa dépendance fréquentielle lors de la croissance et de la chimiothérapie des tumeurs. En ce qui concerne les applications thérapeutiques (chapitres 4 et 5), l'IRM est utilisé comme outil de guidage et de contrôle des ultrasons focalisés. Pour la première fois, une technique de focalisation adaptative basée sur des mesures IRM permet de corriger des aberrations fortes d'un faisceau d'ultrasons. Cette technique non invasive est basée sur la quantification et la maximisation de l'énergie acoustique au point focal par le bais de mesures de la force de radiation acoustique. Cela représente une avancée importante au niveau fondamental. Dans la perspective des HIFU transcraniens chez l'homme, l'intérêt clinique semble d'ores et déjà très pertinent. Parallèlement, un protocole complet de guidage IRM des HIFU transcraniens avant, pendant et après le traitement est ici développé. Il associe un élément ultrasonore focalisé et un système de positionnement dans l'IRM 7T. Trois séquences utilisant la phase du signal IRM sont optimisées pour trois applications complémentaires : imagerie de la force de radiation acoustique, imagerie de la température, et élastographie. Le protocole proposé est testé avec succès in vivo sur des rats sans puis avec tumeurs implantées. Dans le futur proche, ce système de thérapie ultrasonore sous guidage IRM pour le petit animal sera très utile pour étudier les effets des ultrasons sur le cerveau sain et sur des modèles tumoraux. Associé à la technique de focalisation adaptative précédemment mentionnée, ce travail complète le protocole 100% IRM de planification, réalisation et suivi du traitement ultrasonore non invasif du cerveau. Ces techniques sont actuellement en cours de transfert sur l'homme. Bien sûr, comme nous l'avons vu dans les conclusions partielles de chaque chapitre, de nombreuses études sont encore nécessaires pour optimiser certains paramètres, certains outils, les valider cliniquement et leur trouver une place pertinente. Un travail de comparaison avec d'autres méthodes existantes, parfois plus simples, plus anciennes, plus largement disponibles ou moins chères reste aussi à accomplir dans plusieurs cas. Enfin, il va de soi que la validation clinique d'une technique intéressante ne garantie pas son adoption par la communauté médicale, cette adoption dépendant de nombreux critères rationnels comme le coût de l'examen, son accessibilité, sa prise en charge par les systèmes d'assurances sociales, son essor commercial.

There is a growing global need for proper access to radiation therapy. This need exists predominantly in low- and middle-income countries but exists in some high-income countries as well. The solution to this problem is complex and requires changes in government policy, education and technology. The objective of the work contained in this dissertation is the development of a novel external beam radiation therapy system capable of treating a variety of cancers. The intent of this system is to provide a cost-effective radiation therapy system, which can primarily be utilized in low- and middle-income countries. This new system uses kilovoltage rather than megavoltage x-rays and is therefore much more cost-effective. The ultimate purpose of this kilovoltage radiation therapy system is to improve access to radiation therapy worldwide by supplementing current radiation therapy technology. As a first step, the kilovoltage x-ray arc therapy or KVAT system was modeled using the EGSnrc BEAMnrc and DOSXYZnrc Monte Carlo software tools. For this initial study 200 kV arc-therapy was simulated on cylindrical water phantoms of two sizes, each of which contained a variety of planning target volume (PTV) sizes and locations. Additionally, prone and supine partial breast irradiation treatment plans were generated using KVAT. The objective of this work was to determine whether or not skin-sparing could be achieved using the KVAT system while also delivering a clinically relevant dose rate to the PTV. The results of the study indicated that skin-sparing is indeed achievable and that the quality of KVAT treatment plans improves for full 360-degree arcs and smaller PTV sizes. The second step of this project involved the Monte Carlo simulation of KVAT treatment plans for breast, lung and prostate cancer. Spherical PTVs of 3-cm diameter were used for the breast and lung treatment plans while a 4-cm diameter PTV was used for prostate. Additionally, inverse optimization was utilized to make full use of the non-conformal irradiation geometry of KVAT. As a means of comparison, megavoltage treatment plans that could be delivered by a clinical linear accelerator were generated for each patient as well. In order to evaluate the safety of KVAT treatment plans, dose constraints were taken from published Radiation Therapy Oncology Group (RTOG) reports. The results of this study indicated that the 200 kV breast and 225 kV lung KVAT treatment plans were within dose constraints and could be delivered in a reasonable length of time. The 225 kV prostate treatment plan, while technically within dose constraints, delivered a large dose to non-critical healthy tissues due to the limited number of beam angles that did not pass through boney anatomy. It was concluded that plans such as prostate with large volumes of bone present might not be feasible for KVAT treatment. The third step aimed to expand upon previous work and simulated more realistic KVAT treatment plans by using PTV volumes contoured by radiation oncologists. Additionally, this study used a completely redesigned KVAT geometry, which employed a stationary reflection anode and a new collimator design. The design modeled in this study was based upon the specifications of the prototype system under construction by PrecisionRT, a commercial partner. Three stereotactic ablative radiotherapy (SABR) lung patients were selected that had received treatment at the Vancouver Island Cancer Centre. In order to fully cover the PTVs of each patient, spherical sub-volumes were placed within the clinically contoured PTV of each patient. Dose constraints for at-risk organs were taken from an RTOG report on stereotactic body radiation therapy and were used to inversely optimize the 200 kV KVAT treatment plans. The calculated KVAT plans were compared with the clinical 6 MV SABR plans delivered to each patient. The results of this study indicated that KVAT lung plans were within dose constraints for all three patients with the exception of the ribs in the second patient who had a tumor directly adjacent to the rib cage. The fourth and last step of this project was the experimental validation of a simple, proof-of-principle KVAT system. Simple geometric methods were used to design a collimator consisting of two slabs of brass separated by ~6 cm, each with 5 apertures, which would create an array of 5 converging beamlets. The collimator was used with a tabletop x-ray tube system. A rectangular solid water phantom and cylindrical TIVAR 1000 phantom were placed on a rotation stage and irradiated using 360-degree arcs. EBT3 gafchromic film was placed in each phantom to measure two-dimensional dose distributions. Film dose distributions were analyzed and compared to Monte Carlo generated dose distributions. Both the rectangular solid water phantom and cylindrical TIVAR phantom showed skin-sparing effects in their dose distributions. The highest degree of skin-sparing was achieved in the larger, 20 cm diameter cylindrical phantom. Furthermore, the measured film data and calculated metrics of the rectangular phantom were within 10% of the MC calculated values for two out of three films. The discrepancy in the third film can be explained by errors in the experimental setup. In conclusion, the work contained in this dissertation has established the feasibility of a cost-effective kilovoltage arc-therapy system designed to treat deep-seated lesions by means of Monte Carlo simulations and experimental dosimetry. The studies performed so far suggest that KVAT is most suitable for smaller lesions in patient anatomy that does not involve large amounts of boney anatomy. Perhaps most importantly, an experimental study has demonstrated the skin-sparing ability of a simple KVAT prototype. / Graduate / 2020-07-10

The purpose of this work is to evaluate quasi-3D arrays for use with intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) and to determine their clinical relevance. This is achieved using a Delta4 from Scandidos and ArcCheck from Sun Nuclear and the associated software. While certain aspects of these devices and software have been previously evaluated, the main goal of this work is to evaluate the new aspects, such as reconstructing dose on a patient CT set, and extending the capabilities. This includes the capability to reconstruct the dose based on a helical delivery as well as studying the dose to a moving target using measurement-guided motion simulations. It was found that Sun Nuclear's ArcCheck/3DVH system exhibited excellent agreement for dose reconstruction for IMRT/VMAT using a traditional C-arm linear accelerator and stringent 2%/2mm comparison constraints. It also is a powerful tool for measurement-guided dose estimates for moving targets, allowing for many simulations to be performed based on one measurement and the target motion data. For dose reconstruction for a helical delivery, the agreement was not as good for the stringent comparison but was reasonable for the clinically acceptable 3%/3mm comparison. Scandidos' Delta4 shows good agreement with stringent 2%/2mm constraints for its dose reconstruction on the phantom. However, the dose reconstruction on the patient CT set was poor and needs more work. Overall, it was found that quasi-3D arrays are powerful tools for dose reconstruction and treatment plan comparisons. The ability to reconstruct the dose allows for a dose resolution comparable to the treatment plan, which negates the previous issues with inadequate sampling and resolution issues found when just comparing the diodes. The ability to quickly and accurately compare many plans and target motions with minimum setup makes the quasi-3D array an attractive tool for both commissioning and patient specific quality assurance.