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"September 2004" / Bibliography: leaves 236-262. / xxxi, 262 leaves : ill., plates (col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 2004

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"This thesis presents an ultrasound technique for measuring the absolute integrated backscatter (IBS) of arterial wall structures through an intervening inhomogeneous soft tissue layer. The aberrating effect of this tissue layer is minimized by normalizing the measured IBS from the wall region of interest with the IBS from an adjacent range cell in blood. The technique may become a tool to differentiate between stable and vulnerable plaques in the carotid artery."

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Atherosclerotic plaques with high probability of rupture show the presence of a hot spot due to the accumulation of inflammatory cells. This study utilizes two and three dimensional (2-D and 3-D) arterial geometries containing an atherosclerotic plaque experiencing different levels of inflammation and uses models of heat transfer analysis to determine the temperature distribution in the plaque region. The 2-D studies consider three different vessel geometries: a stenotic straight artery, a bending artery and an arterial bifurcation which model a human aorta, a coronary artery and a carotid bifurcation, respectively. The 3-D model considers a stenotic straight artery using realistic and simplified geometries. Three different blood flow cases are considered: steady-state, transient state and blood flow reduction. In the 3-D model, thermal stress produced by local inflammation is estimated to determine the effect of inflammation over plaque stability. For fluid flow and heat transfer analysis, Navier-Stokes equations and energy equation are solved; for structural analysis, the governing equations are expressed in terms of equilibrium equation, constitutive equation, and compatibility condition, which are are solved using the multi-physics software COMSOL 3.3 (COMSOL, Inc.). Our results indicate that the best location to measure plaque temperature in the presence of blood flow is recommended between the middle and the far edge of the plaque. The blood flow reduction leads to a non-uniform temperature increase ranged from 0.1 to 0.25 oC in the plaque/lumen interface. In 3-D realistic model, the multiple measuring points must be considered to decrease the potential error in temperature measurement even within 1 or 2 mm at centerline region of plaque. The most highly thermal stressed regions with the value of 1.45 Pa are observed at the corners of lipid core and the plaque/lumen interface. The mathematical model developed provides a tool to analyze the factors affecting heat transfer at the plaque surface. The results may contribute to the understanding of the relationship between plaque temperature and the likelihood of rupture, and also provide a tool to better understand arterial wall temperature measurements obtained with novel catheters.

A brief review was provided of lipid metabolism, mechanisms of lipid lowering and coronary heart disease risk factors (including the role of antioxidants). In addition, studies of lipid-lowering and other anti-atherosclerotic effects of garlic materials were also reviewed. Evaluation and development of techniques required to perform studies of the anti-atherosclerotic effects of garlic were implemented, including evaluation of methods for measuring total antioxidant capacity and the development of methods for the rapid isolation of low density lipoprotein (LDL). The main objective of this project was to investigate the effects of garlic upon plasma lipids in rats and healthy human subjects and the effects upon antioxidant status in healthy human subjects. In a long-term study with old male rats, a low dose of garlic oil (c. O.5mg/Kg body weight/day) for 12.5 weeks provided in a high fat diet produced no significant reduction in plasma lipids or glucose. Upward trends in plasma lipids early in the treatment period were similar to those reported from several previous studies in which eventual reductions in plasma lipids were observed suggesting the possibility of a small effect of garlic oil upon lipid metabolism. Two randomised, double-blind, placebo-controlled human studies were carried out to investigate the effects of capsules containing garlic oil dissolved in vegetable oil upon coronary heart disease risk factors in normal subjects. In the first study, 8.2 mg/day of garlic oil (or placebo) capsules were given to 51 subjects over an I 1- week period. 95% confidence intervals were calculated for differences between garlic oil and placebo groups of changes in plasma lipids, glucose and total antioxidant capacity between baseline and end-oftreatment. No significant effects were observed, but it was found that plasma lipids and glucose trends were more favourable with garlic oil treatment. Effects of garlic oil over placebo for cholesterol-related variables and glucose were in opposite directions for males and females and this interaction between genders reached significance for high density lipoprotein cholesterol, total cholesterol/high density lipoprotein cholesterol ratio, calculated low density lipoprotein cholesterol and glucose of plasma. The strong gender effect of garlic oil evidenced for plasma lipids and glucose implies potent effects of garlic oil and suggests future garlic studies should include gender analyses. In the second human study, 12 mg/day garlic oil (or placebo) capsules were given to 27 trained young male athletes for 16 weeks. 95% confidence intervals were calculated for differences between garlic oil and placebo groups of changes in plasma lipids, total antioxidant capacity and LDL composition between baseline and end-of-treatment. It was found that the reduction in plasma triglycerides (p=O.09) of the garlic oil group in comparison with the placebo group was accompanied by increases in density, a significant reduction in triglycerides / protein and a trend towards reduction of cholesterol/protein of the LDL fraction. A trend towards reduced total antioxidant capacity / protein of LDL appear to reflect garlic oil effects upon lipid composition of LDL rather than directly upon antioxidants. Non-significant trends towards small improvements in maximal oxygen intake test-duration and less plasma glucose depletion with garlic oil were observed. Overall, the results from the human studies provide some encouragement to the view that garlic oil could reduce coronary heart disease risk in normal persons and that this possibility deserves further investigation.

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The goal of this research was to demonstrate the potential of spectral CT for the discrimination of vulnerable atherosclerotic plaques. It was proposed that spectral CT has the potential to identify the presence of specific markers for vulnerable plaques: iron deposits and lipid core. A spectral micro-CT system incorporating the latest Medipix spectroscopic photon- counting detectors was commissioned for this purpose. Using spectroscopic methods developed with this system, it was possible to distinguish the presence of iron deposits and lipid core within ex vivo atherosclerotic plaques. Atherosclerosis or hardening of arteries is a systemic disease of the vessel wall that occurs in the aorta, carotid, coronary and peripheral arteries. It is characterised by the deposition of calcified plaques on the innermost layer of the artery wall. Vulnerable plaques are unstable, prone to rupture and put the person at risk of cardiovascular events and strokes. Factors that may lead to plaque instability are lipid content and iron deposits. This preclinical study is a precursor to the development of a clinical technique that will enable vulnerable atherosclerotic plaques to be identified in vivo prior to treatment or removal. Following a preliminary study on atherosclerotic plaques with a prototype system, the MARS-CT3 spectral micro-CT system incorporating Medipix3 was developed and commissioned for further plaque studies. The spectral CT data sets acquired by this system were assessed visually for morphology and analysed for material composition using a linear algebra method. The results were correlated with photography and histology (the histology is the current gold standard). The presence of iron and lipid can be differentiated from the background soft-tissue using a linear algebra method. However the quantification of iron in the presence of calcium is not currently possible without additional data or constraints. Nevertheless the presence of iron deposits within the plaques can be distinguished in the high resolution MARS-CT images and has been correlated with photographic and histological evidence. Thus, using the high spatial resolution spectral data from MARS-CT, the discrimination of lipid core and iron deposits within ex vivo advanced human atherosclerotic plaques is feasible. This may provide the basis for the development of a clinical technique that will identify vulnerable plaques in vivo by high resolution spectral CT.

Thesis (M.S.)--California Polytechnic State University, 2009. / Title from PDF title page; viewed on July 8, 2009. "January 2009." "In partial fulfillment of the requirements for the degree [of] Master of Science in Engineering with a specialization in Biomedical Engineering." "Presented to the faculty of California Polytechnic State University, San Luis Obispo." Major professor: Robert Crockett, Ph.D. Includes bibliographical references (p. 78-88).