Osteoporosis is a major public health concern with origins in childhood and is potentially linked to childhood obesity. This study used novel approaches in bone imaging to characterize skeletal development in girls and to assess the influence of whole body and regional soft tissue composition on bone material, structural and geometric properties, the primary determinants of bone strength, controlling for important covariates such as maturation, diet and physical activity. Prospective analyses were conducted to assess associations between measures of total body fat (TBFM) and android fat masses (AFM) and skeletal muscle fat (SMF) content on bone mineral content, density and strength. The results showed that higher TBFM and AFM were inversely associated with changes in cortical bone sites of the femur and tibia. These findings suggest that gains in abdominal adiposity during the pre- and early- pubertal years may contribute to suboptimal bone development and skeletal fragility later in life. The analyses also showed inverse associations between baseline muscle density of the thigh and calf with 2-year changes in bone strength and bone density of the metaphyseal and diaphyseal sites of the femur and tibia. This paradoxical relationship between SMF and bone outcomes was explained by subsequent analyses showing that girls exhibiting larger gains in muscle density experienced larger increases in bone density and strength compared to girls who did not significantly increase muscle density. These findings suggest that fatty infiltration of skeletal muscle contributes to suboptimal bone development in peri-pubertal girls. Further longitudinal analyses were conducted to examine the individual effects of the muscle-bone unit components on 2-year changes in bone strength. These results showed that muscle size contributed to gains in bone strength, independent of its mechanostat effect on BMC. These results underscore the importance of muscle size for promoting bone development and bone strength during growth. A final set of analyses were conducted to examine the effects of dietary fatty acids on bone development. The results of these analyses suggest that while decreasing intakes of AA n-6 FA may benefit bone health, higher intakes n-3 FAs may benefit tibia bone density development in young girls.

The present work expose a technique of estimation of optimal direction for placing dental implant. A volumetric computed tomography (CT) scan is used as a help of the following searches. The work offers criteria of the optimal implant placement direction and methods of evaluation on direction’s significance. The technique utilizes structure tensor to find a normal to the jawbone surface. Direction of that normal is then used as initial direction for search of optimal direction. The technique described in the present work aimed to support doctor’s decisions during dental implantation treatment.

The effects of porous medium heterogeneity on methane hydrate formation, water flow through the heterogeneous hydrate-bearing sand, and hydrate dissociation were observed in an experiment using a heterogeneous sand column with prescribed heterogeneities. X-ray computed tomography (CT) was used to monitor saturation changes in water, gas, and hydrate during hydrate formation, water flow, and hydrate dissociation. The sand column was packed in several segments having vertical and horizontal layers with two distinct grain-size sands. The CT images showed that as hydrate formed, the water and hydrate saturations were dynamically redistributed by variations in capillary strength of the medium (the tendency for a material to imbibe water), which changed with the presence and saturation of hydrate. Water preferentially flowed through fine sand near higher hydrate-saturation regions where the capillary strength was elevated relative to the lower hydrate saturation regions. Hydrate dissociation initiated by depressurization varied with different grain sizes and hydrate saturations.

Research on sex and gender in chronic obstructive pulmonary disease (COPD) has primarily focused on differences in pulmonary function. Detailed gender- and sex-based analyses of other aspects of COPD, including epidemiology, risk factors other than cigarette smoke, pathophysiology, and measurement tools are warranted. In Chapter Two we analyzed administrative health services data to compare the prevalence, mortality and use of drugs and spirometry in men and women with COPD. Contrary to recent predictions, we did not detect a dramatic increase in the prevalence or mortality of COPD over time in women compared to men. We discuss how different coding practices in medical billing can impact the results. In Chapter Three we examined sex differences in COPD phenotypes. We hypothesized that male smokers would have more emphysema whereas female smokers would have more airway wall remodeling using data from high resolution computed tomography (HRCT) scans. We did detect more emphysema in male smokers but there was no evidence of increased airway remodeling in women. We discuss the limits of HRCT to detect airway differences in women and men. In Chapter Four we examined the use of HRCT in assessing emphysema. We hypothesized that the computer-derived estimates of emphysema (the fractal value and the % low attenuation area (%LAA)) would differentiate COPD from non-COPD as accurately as the radiologist’s emphysema scores, and would provide similar predictions in both men and women. Instead, we found that the subjective rating of emphysema best differentiated COPD, and the fractal value (a measure of emphysematous lesion size) better differentiated COPD compared with an established objective measurement, the %LAA. These results were generally the same in men and women. In Chapter Five we examined characteristics of COPD in women exposed to biomass smoke. We hypothesized that biomass smoke would induce an airway disease-predominant phenotype. We found that women with biomass smoke-exposed COPD had greater airway remodeling and less emphysema than women with tobacco smoke-exposed COPD. In summary, these findings suggest that sex and gender differences are present in COPD epidemiology and pathophysiology. However, current research measurement tools may limit the ability to accurately measure these differences.

This thesis is an investigation of diagnostic staging and palliative radiation therapy (RT) for appendicular osteosarcoma (OSA) in dogs. Osteosarcoma is a common, highly metastatic primary bone tumour of dogs. The purpose of the first study was to assess the utility of whole body computed tomography (CT) in evaluation of metastasis in dogs with primary appendicular OSA. The objectives were to determine the utility of whole body CT as a staging tool for dogs with appendicular OSA, compare the lesion detection rate of bone scintigraphy, long bone survey radiography and whole body CT in dogs with appendicular OSA and determine the prevalence of CT-detected lung metastasis in dogs with appendicular OSA that have normal thoracic radiographs. This was a prospective cross-sectional observational study involving fifteen dogs. Test modalities were assessed against a construct reference standard for detection of bone metastasis and thoracic radiographs negative for metastatic lesions were compared against thoracic CT. Bone scintigraphy identified 5 bone lesions in 4 dogs with 2 false positive and 2 false negative results. No lesions were identified on survey radiographs or CT during blinded assessment. CT was useful for further characterizing lesions identified by bone scintigraphy. Thoracic CT identified both definitive and equivocal lesions not visible radiographically. Four dogs had equivocal ground glass pulmonary lesions on CT; 3 of these lesions progressed to radiographically discrete nodules. Overall, bone scintigraphy was the only modality that identified metastatic bone lesions. Whole body CT did not appear to be useful as alternative to bone scintigraphy; however, it may have some utility as an adjunctive diagnostic modality. Thoracic CT identified pulmonary lesions that were not visible radiographically. Ground glass pulmonary lesions in dogs should be considered suspicious for metastasis and serially monitored. The purpose of the second study was to retrospectively assess factors affecting survival time in dogs undergoing palliative RT for appendicular OSA. Fifty dogs undergoing a palliative RT protocol for spontaneous primary appendicular bone tumours were included and divided into treatment groups based on treatments administered in addition to RT. Median survival times (MST) were longest for dogs receiving RT and chemotherapy (307 days; 95%CI= 279-831) and shortest in dogs receiving RT and pamidronate (69 days; 95%CI=47-112 days). The difference in MST between dogs who received pamidronate and those who did not in this population was statistically significant on univariate (p=0.039) and multivariate analysis (p=0.0015). The addition of chemotherapy into any protocol improved survival (p<0.001). Based on the findings in this study, chemotherapy should be recommended in addition to a palliative RT protocol to improve survival of dogs with primary appendicular bone tumours. When combined with RT +/- chemotherapy, pamidronate decreased MST. / Ontario Veterinary College Pet Trust Fund

Although mammals are the most commonly utilized laboratory animal, laboratory animal medicine continually seeks to replace them with animals of lower phylogenic classification. Fish are becoming increasingly important as investigators seek alternative animal models for research. Fish can provide an economical and feasible alternative to typical mammalian models; moreover, many fish, which have comparatively short life spans, can easily reproduce in the laboratory. One key area of animal health research in which fish have been underutilized is the field of advanced imaging. Although many images of fish have been captured through the use of computed tomography (CT), radiography, and ultrasonography, these images have been primarily utilized for anatomical study. In addition, fish have never before been studied with positron emission tomography/ computed tomography (PET/CT). My objectives were to determine if these imaging techniques can be used to obtain physiological information from fish, therefore making it more likely that fish can be utilized as replacement animals using these new imaging techniques (CT, PET/CT). I performed two different types of studies to assess the potential application of advanced imaging techniques to fish. In the first experiment, microCT was used to characterize otolith deformity in vitamin C deficient captive-raised red drum and relate the deformity to behavioral and physiological changes. I found that the normal and abnormal fish had statistically significant differences in behavior, cortisol levels, and otolith volume and density. MicroCT assessment of abnormal fish revealed operculum abnormalities, malocclusions, and several types of otolith malformations. Therefore, the affected fish had not only an abnormal skeletal appearance but also significantly abnormal behavior and cortisol responses. In the second experiment, fluorodeoxyglucose-positron emission tomography/ computed tomography (FDG-PET/CT) was used to quantify glucose uptake in select organs prior to carcinogenesis studies in fish. The quantified glucose uptake was compared to published data on humans, mice, and dogs. Rapid, quantifiable glucose uptake was demonstrated, particularly in brain, kidneys, and liver in all imaged fish species. Glucose uptake in the major organ systems of fish was closer to that in humans than uptake in mice or dogs, indicating that fish may serve as an effective alternative animal model for tumor studies using this technology. Other applications for this technique in fish may include metabolism studies and screening for environmental carcinogenesis. I found that both microCT and PET/CT imaging provided useful and meaningful results. In addition, the use of non-invasive scanning allows for re-use of fish, thus reducing the number of animal models used in experiments. These experiments suggest that fish will be good replacement models for mammals using these advanced imaging techniques.

Cobalt 60 (Co-60) radiation therapy is a simple and reliable method of treating cancer by irradiating treatment volumes within the patient with high energy gamma rays. Medical linear accelerators (linacs) began to replace Co-60 units during the 1960’s in more developed countries, but Co 60 has remained the main source of radiotherapy treatment in less developed countries around the world. As a result, technological advancements made in more developed countries to deliver more precise radiation treatment that improves patient outcome have not been clinically applied to Co-60 machines. The medical physics group at the Cancer Centre of Southeastern Ontario has shown that these same technological advancements can be applied to Co-60 machines which would increase the accessibility of these modern improvements in radiotherapy treatment. However, for these modern treatments to improve patient outcome they require more precise localization of the patient prior to therapy. In more developed countries, this is currently provided by comparing computed tomography (CT) used for treatment planning with images acquired on the linac immediately before treatment. In the past decade, cone-beam CT (CBCT) has been developed to provide 3D CT images of the patient immediately prior to treatment on a linac. This imaging modality would also be ideal for patient localization when conducting modern Co-60 treatments since it would only require the addition of an imaging panel to produce CBCT images using the Co-60 source. A prototype Co-60 CBCT imaging system was implemented and characterized. Image noise, contrast, spatial resolution, and artifacts were studied. Algorithms to reduce the image artifacts were implemented and found to improve perceived image quality. The imaging system was found to have a ~1.8 mm high-contrast spatial resolution and the ability to detect 3 cm low-contrast soft-tissue structures in water. Anthropomorphic phantoms were also imaged and the observed anatomy in Co-60 CBCT images was comparable to kilovoltage CT. These results are comparable to clinically relevant linac-based CBCT using high energy X rays of similar energies to Co-60 gamma rays. This suggests that Co-60 CBCT should be able to provide the necessary images to localize patients for modern Co-60 radiation treatments. / Thesis (Master, Physics, Engineering Physics and Astronomy) -- Queen's University, 2010-11-30 13:40:07.61

Dual-phase (DP) sheet steels are a class of advanced high strength steels which boast a desirable combination of properties for the forming of automotive components, including: high strength, continuous yielding behaviour, and a high initial work hardening rate. The higher strength of DP steels relative to predecessors used to form automotive components allows for a reduction in part gauge, translating to the potential for reduced automobile weight, emissions, and fuel consumption. However, a form of premature failure during component forming known as `shear fracture' has become a prominent challenge to manufacturers' adoption of DP steels. Martensite particles in DP steel microstructures act as nucleation sites for the development of void damage during deformation, resulting in a deleterious effect upon formability and thought to contribute to the observed shear fractures. This dissertation contributes to the overall goal of offering guidance for the improvement of DP steel microstructures for more desirable fracture behaviour. Specifically, the role of non-ferritic phase/constituent (NFP) volume percent and spatial distribution in the accumulation of void damage in DP steels was investigated. Void damage accumulation in ten DP steel microstructural variants tested to failure under near plane-strain deformation was qualified and quantified in three dimensions using an X-ray micro-computed tomography technique. These results were correlated to the microstructural parameters of the variants, which clearly indicated the detrimental effects of NFP banding in DP steels. It was observed that DP microstructures with increased severity of NFP banding (generally aligned in the sheet rolling direction) incurred a reduced strain to failure. Often, microstructural variants with NFP bands aligned transverse to the major loading direction incurred a reduced strain to failure, accumulated a greater number of voids, and exhibited a larger void volume percent than a specimen with oppositely oriented NFP bands. Void damage spatial distribution was generally reflective of the spatial distribution of the most coarse NFP bands through the sheet thickness. In microstructural variants with NFP bands aligned transverse to the major loading direction, accumulated void damage was often observed to be highly elongated in the direction of NFP banding. / Thesis (Master, Mechanical and Materials Engineering) -- Queen's University, 2011-09-30 11:49:18.645

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