Light transport simulation aims at the numerical computation of the propagation of visible electromagnetic energy in macroscopic environments. In this thesis, we develop the foundations for a modern theory of light transport simulation, unveiling the geometric structure of the continuous theory and providing a formulation of computational techniques that furnishes remarkably efficacy with only local information. Utilizing recent results from various communities, we develop the physical and mathematical structure of light transport from Maxwell's equations by studying a lifted representation of electromagnetic theory on the cotangent bundle. At the short wavelength limit, this yields a Hamiltonian description on six-dimensional phase space, with the classical formulation over the space of "positions and directions" resulting from a reduction to the five-dimensional cosphere bundle. We establish the connection between light transport and geometrical optics by a non-canonical Legendre transform, and we derive classical concepts from radiometry, such as radiance and irradiance, by considering measurements of the light energy density. We also show that in idealized environments light transport is a Lie-Poisson system for the group of symplectic diffeomorphisms, unveiling a tantalizing similarity between light transport and fluid dynamics. Using Stone's theorem, we also derive a functional analytic description of light transport. This bridges the gap to existing formulations in the literature and naturally leads to computational questions. We then address one of the central challenges for light transport simulation in everyday environments with scattering surfaces: how are efficient computations possible when the light energy density can only be evaluated pointwise? Using biorthogonal and possibly overcomplete bases formed by reproducing kernel functions, we develop a comprehensive theory for computational techniques that are restricted to pointwise information, subsuming for example sampling theorems, interpolation formulas, quadrature rules, density estimation schemes, and Monte Carlo integration. The use of overcomplete representations makes us thereby robust to imperfect information, as is often unavoidable in practical applications, and numerical optimization of the sampling locations leads to close to optimal techniques, providing performance which considerably improves over the state of the art in the literature.

Doctor of Philosophy / Department of Mechanical and Nuclear Engineering / Douglas S. McGregor / A novel design of neutron sensor was investigated and developed. The perforated, or micro-structured, diode neutron sensor is a concept that has the potential to enhance neutron sensitivity of a common solid-state sensor configuration. The common thin-film coated diode neutron sensor is the only semiconductor-based neutron sensor that has proven feasible for commercial use. However, the thin-film coating restricts neutron counting efficiency and severely limits the usefulness of the sensor. This research has shown that the perforated design, when properly implemented, can increase the neutron counting efficiency by greater than a factor of 4. Methods developed in this work enable detectors to be fabricated to meet needs such as miniaturization, portability, ruggedness, and adaptability. The new detectors may be used for unique applications such as neutron imaging or the search for special nuclear materials. The research and developments described in the work include the successful fabrication of variant perforated diode neutron detector designs, general explanations of fundamental radiation detector design (with added focus on neutron detection and compactness), as well as descriptive theory and sensor design modeling useful in predicting performance of these unique solid-state radiation sensors. Several aspects in design, fabrication, and operational performance have been considered and tested including neutron counting efficiency, gamma-ray response, perforation shapes and depths, and silicon processing variations. Finally, the successfully proven technology was applied to a 1-dimensional neutron sensor array system.

Mounting evidence suggests that the superposition of anatomical clutter in x-ray chest radiography poses a major impediment to the detectability of subtle lung nodules. Through decomposition of projections acquired using different x-ray energy spectra, dual-energy (DE) imaging offers to dramatically improve lung nodule conspicuity. The development of a high-performance DE chest imaging system is reported, with design and implementation guided by fundamental imaging performance metrics. Analytical and experimental studies of imaging performance guided the optimization of key acquisition technique parameters, including x-ray filtration, allocation of dose between low- and high-energy projections, and peak-kilovoltage selection. To minimize anatomical misregistration between images, a cardiac gating system was designed and implemented to direct x-ray exposures to within the quiescent period of the heart cycle. The instrumentation and optimal imaging techniques have been incorporated in a DE imaging prototype system now deployed in a clinical study to evaluate the diagnostic performance of DE imaging.

Mounting evidence suggests that the superposition of anatomical clutter in x-ray chest radiography poses a major impediment to the detectability of subtle lung nodules. Through decomposition of projections acquired using different x-ray energy spectra, dual-energy (DE) imaging offers to dramatically improve lung nodule conspicuity. The development of a high-performance DE chest imaging system is reported, with design and implementation guided by fundamental imaging performance metrics. Analytical and experimental studies of imaging performance guided the optimization of key acquisition technique parameters, including x-ray filtration, allocation of dose between low- and high-energy projections, and peak-kilovoltage selection. To minimize anatomical misregistration between images, a cardiac gating system was designed and implemented to direct x-ray exposures to within the quiescent period of the heart cycle. The instrumentation and optimal imaging techniques have been incorporated in a DE imaging prototype system now deployed in a clinical study to evaluate the diagnostic performance of DE imaging.

Doctor of Philosophy / Department of Physics / Dean A. Zollman / In this study we explored students' transfer of learning in the X-ray medical imaging context, including the X-ray-based computer-assisted tomography (or CAT). For this purpose we have conducted a series of clinical and teaching interviews. The investigation was a part of a bigger research effort to design teaching-learning materials for pre-medical students who are completing their algebra-based physics course. Our students brought to the discussion pieces of knowledge transferred from very different sources such as their own X-ray experiences, previous learning and the mass media. This transfer seems to result in more or less firm mental models, although often not internally consistent or coherent. Based on our research on pre-med students' models of X-rays we designed a hands-on lab using semi-transparent Lego bricks to model CAT scans. Without "surgery" (i.e. without intrusion into the Lego "body") students determined the shape of an object, which was built out of opaque and translucent Lego bricks and hidden from view. A source of light and a detector were provided upon request. Using a learning cycle format, we introduced CAT scans after students successfully have completed this task. By comparing students' ideas before and after teaching interview with the groups of 2 or 3 participants, we have investigated transfer of learning from basic physics and everyday experience to a complex medical technology and how their peer interactions trigger and facilitate this process. During the last phase of our research we also introduced a CAT-scan simulation problem into our teaching interview routine and compared students' perception of this simulation and their perception of the hands-on activity.

Des avancements récents dans le domaine de la radiothérapie stéréotaxique permettent à un nombre grandissant de patients de recevoir un traitement non-invasif pour le cancer du foie. L’une des méthodes utilisées consiste à suivre le mouvement de la tumeur à l’aide de marqueurs radio-opaques insérés dans le foie grâce au système de suivi de l’appareil de traitement CyberKnife. Or, l’insertion de ces marqueurs est parfois trop invasive pour certains patients souffrant de maladie du foie avancée. Ces patients ont souvent un historique de chirurgie qui permet d’utiliser les agrafes chirurgicales déjà présentes dans leur foie dans le but de suivre leur tumeur. Cette nouvelle approche au traitement des tumeurs du foie est investiguée dans cette étude afin d’en déterminer les paramètres optimaux pour une meilleure pratique thérapeutique. L’expérimentation sur fantôme anthropomorpique a permis de conclure que le contraste des agrafes dans leur milieu augmente lors de l’augmentation des paramètres d’imagerie (kilovoltage et milliampérage de l’appareil de radiographie). D’autre part, l’erreur commise par le système CyberKnife dans l’identification des agrafes pour le suivi a été mesurée comme étant supérieure à celle sur l’emplacement des marqueurs radiologiques de platine (environ 1 mm contre moins de 1 mm). Cette erreur est considérée comme acceptable dans le contexte de ce type de traitement particulier. Enfin, une analyse gamma de l’impact dosimétrique du suivi par agrafes a montré qu’il était approximativement équivalent à celui par marqueurs de platine. De ces observations on conclue que le traitement des tumeurs du foie avec suivi des agrafes chirurgicales est valide et peut être amélioré suivant certaines recommandations cliniques. / Recent progress in stereotactic body radiation therapy allows an ever larger number of people to receive non-invasive treatment for liver cancer. One of the methods that were developed involves tracking the tumor’s movements, using radio-opaque markers which are inserted into the liver of the patient, with the help of the tracking system of the CyberKnife. However, the insertion of these markers is sometimes too invasive for patients with poor liver condition. These patients often have a history of surgery which allows the tracking of surgical clips that are already present in the liver as a surrogate for the tumor. This new approach to treating liver cancer is investigated in the present study in order to identify the optimal parameters for a better practice of this therapy. An anthropomorphic phantom experiment lead to the conclusion that the clip contrast in the tissue increases with an increase of the two imaging parameters (kV and mA of the x-ray tube). In addition, the error that was made on the identification of the position of clips by the CyberKnife system was measured as being slightly superior to the error on platinum marker positions (approximately 1 mm vs less than 1 mm). This error is considered acceptable in the context of this particular type of treatment. Finally, a gamma analysis of the dosimetric impact of clip tracking shows that it is approximately equivalent to that of platinum marker tracking. From these observations, we conclude that the treatment of liver tumors using surgical clips is valid and can be improved following this study’s clinical recommendations.

Dans la pratique actuelle de la curiethérapie à bas débit, l'évaluation de la dose dans la prostate est régie par le protocole défini dans le groupe de travail 43 (TG-43) de l'American Association of Physicists in Medicine. Ce groupe de travail suppose un patient homogène à base d'eau de même densité et néglige les changements dans l'atténuation des photons par les sources de curiethérapie. En considérant ces simplifications, les calculs de dose se font facilement à l'aide d'une équation, indiquée dans le protocole. Bien que ce groupe de travail ait contribué à l'uniformisation des traitements en curiethérapie entre les hôpitaux, il ne décrit pas adéquatement la distribution réelle de la dose dans le patient. La publication actuelle du TG-186 donne des recommandations pour étudier des distributions de dose plus réalistes. Le but de ce mémoire est d'appliquer ces recommandations à partir du TG-186 pour obtenir une description plus réaliste de la dose dans la prostate. Pour ce faire, deux ensembles d'images du patient sont acquis simultanément avec un tomodensitomètre à double énergie (DECT). Les artéfacts métalliques présents dans ces images, causés par les sources d’iode, sont corrigés à l'aide d’un algorithme de réduction d'artefacts métalliques pour DECT qui a été développé dans ce travail. Ensuite, une étude Monte Carlo peut être effectuée correctement lorsque l'image est segmentée selon les différents tissus humains. Cette segmentation est effectuée en évaluant le numéro atomique effectif et la densité électronique de chaque voxel, par étalonnage stoechiométrique propre au DECT, et en y associant le tissu ayant des paramètres physiques similaires. Les résultats montrent des différences dans la distribution de la dose lorsqu'on compare la dose du protocole TG-43 avec celle retrouvée avec les recommandations du TG-186. / In current low dose rate brachytherapy practice, dose evaluation within the prostate is govern by the protocol defined by the task group 43 (TG-43) of the American Association of Physicist in Medicine. This task group assumes a homogeneous water based patient with invariable density. They also disregard the changes in photon attenuation through neighbouring brachytherapy sources. With the introduction of these simplifications, dose calculations are easily solved using an equation proposed in this protocol. Although this task group helped create a uniform practice of brachytherapy treatments between hospitals, it does not properly described the actual dose distribution within the patient. The current publication of TG-186 gives recommendations to study these dose distribution more realistically. The purpose of this Master's thesis is to apply these recommendations from TG-186 to obtain a more realistic description of the dose. In order to proceed, two sets of patient images are acquired with a dual energy computed tomography (DECT). These images are corrected for metallic artifacts, which are highly present in the scanned images, using DECT metallic artifact reduction algortithm, developped in this work. Afterwords, a Monte Carlo study can be performed by properly identifying the environment with human tissues. This segmentation is performed by evaluating the effective atomic number and electronic density of each voxel using a DECT stoichiometric calibration, and allocating the tissue having the closest resemblance to these physical parameters. The results show clear differences in dose distribution when comparing TG-43 protocole with TG-186 recommendations.

Bibliography: leaves 230-294. / xiii, 294 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Analyses in detail a native small fragment of hCG/[beta] hCG subunit, the [beta]-core hCG fragment which is found in large amounts in urine and may be of clinical importance. The aims were to purify the fragment, analyse its protein and carbohydrate structure, develop direct assay methods for its measurement, and to examine it's distribution in body fluids and it's relationship with the intact hCG molecule during pregnancy. / Thesis (Ph.D.)--University of Adelaide, Dept. of Obstetrics and Gynaecology, 1993

The goal of radiotherapy is to operate within the therapeutic window - delivering doses of ionizing radiation to achieve locoregional tumour control, while minimizing normal tissue toxicity. A greater therapeutic ratio can be achieved by utilizing radiosensitizing agents designed to enhance the effects of radiation at the tumour. Gold nanoparticles (AuNP) represent a novel radiosensitizer with unique and attractive properties. AuNPs enhance local photon interactions, thereby converting photons into localized damaging electrons. Experimental reports of AuNP radiosensitization reveal this enhancement effect to be highly sensitive to irradiation source energy, cell line, and AuNP size, concentration and intracellular localization. This thesis explored the physics and some of the underlying mechanisms behind AuNP radiosensitization. A Monte Carlo simulation approach was developed to investigate the enhanced photoelectric absorption within AuNPs, and to characterize the escaping energy and range of the photoelectric products. Simulations revealed a 10^3 fold increase in the rate of photoelectric absorption using low-energy brachytherapy sources compared to megavolt sources. For low-energy sources, AuNPs released electrons with ranges of only a few microns in the surrounding tissue. For higher energy sources, longer ranged photoelectric products travelled orders of magnitude farther. A novel radiobiological model called the AuNP radiosensitization predictive (ARP) model was developed based on the unique nanoscale energy deposition pattern around AuNPs. The ARP model incorporated detailed Monte Carlo simulations with experimentally determined parameters to predict AuNP radiosensitization. This model compared well to in vitro experiments involving two cancer cell lines (PC-3 and SK-BR-3), two AuNP sizes (5 and 30 nm) and two source energies (100 and 300 kVp). The ARP model was then used to explore the effects of AuNP intracellular localization using 1.9 and 100 nm AuNPs, and 100 and 300 kVp source energies. The impact of AuNP localization was most significant for low-energy sources. At equal mass concentrations, AuNP size did not impact radiosensitization unless the AuNPs were localized in the nucleus. This novel predictive model of AuNP radiosensitization could help define the optimal use of AuNPs in potential clinical strategies by determining therapeutic AuNP concentrations, and recommending when active approaches to cellular accumulation are most beneficial.

The goal of radiotherapy is to operate within the therapeutic window - delivering doses of ionizing radiation to achieve locoregional tumour control, while minimizing normal tissue toxicity. A greater therapeutic ratio can be achieved by utilizing radiosensitizing agents designed to enhance the effects of radiation at the tumour. Gold nanoparticles (AuNP) represent a novel radiosensitizer with unique and attractive properties. AuNPs enhance local photon interactions, thereby converting photons into localized damaging electrons. Experimental reports of AuNP radiosensitization reveal this enhancement effect to be highly sensitive to irradiation source energy, cell line, and AuNP size, concentration and intracellular localization. This thesis explored the physics and some of the underlying mechanisms behind AuNP radiosensitization. A Monte Carlo simulation approach was developed to investigate the enhanced photoelectric absorption within AuNPs, and to characterize the escaping energy and range of the photoelectric products. Simulations revealed a 10^3 fold increase in the rate of photoelectric absorption using low-energy brachytherapy sources compared to megavolt sources. For low-energy sources, AuNPs released electrons with ranges of only a few microns in the surrounding tissue. For higher energy sources, longer ranged photoelectric products travelled orders of magnitude farther. A novel radiobiological model called the AuNP radiosensitization predictive (ARP) model was developed based on the unique nanoscale energy deposition pattern around AuNPs. The ARP model incorporated detailed Monte Carlo simulations with experimentally determined parameters to predict AuNP radiosensitization. This model compared well to in vitro experiments involving two cancer cell lines (PC-3 and SK-BR-3), two AuNP sizes (5 and 30 nm) and two source energies (100 and 300 kVp). The ARP model was then used to explore the effects of AuNP intracellular localization using 1.9 and 100 nm AuNPs, and 100 and 300 kVp source energies. The impact of AuNP localization was most significant for low-energy sources. At equal mass concentrations, AuNP size did not impact radiosensitization unless the AuNPs were localized in the nucleus. This novel predictive model of AuNP radiosensitization could help define the optimal use of AuNPs in potential clinical strategies by determining therapeutic AuNP concentrations, and recommending when active approaches to cellular accumulation are most beneficial.