Thesis (M.S.)--University of Michigan, 1965.

Thesis (M.S.)--University of Michigan, 1983.

Thesis--Karolinska Institute. / Includes reprints of four supporting articles. Includes bibliographical references (leaves 43-47).

Thesis--Karolinska Institute. / Includes reprints of four supporting articles. Includes bibliographical references (leaves 43-47).

Atherosclerotic plaque ruptures have been determined as the most common underlying cause of acute coronary syndromes and stroke. Currently, the standard of care for plaque rupture risk is based on the amount of luminal stenosis presented in a particular vessel; however, X-ray angiographic studies have shown that plaques at risk of rupture generally show <50% luminal narrowing. These findings explicate the need for other, more accurate methods of identifying problem lesions prior to the rupture event. Unfortunately, the study of thrombotic events and vulnerable plaque lesions in humans is difficult due to the spontaneity of rupture and the lengthy time course of disease progression. To further the understanding of plaque rupture risk in light of vulnerability detection, a rabbit model of atherothrombosis was used in conjunction with magnetic resonance imaging (MRI). MRI has been validated as a suitable imaging modality for in vivo, non-invasive detection of atherosclerosis and has provided quantitative predictors of plaques at risk of rupture. Additionally, the rabbit model has been shown, histologically, to present 6 of the 8 human plaque types classified by the American Heart Association. The first portion of this dissertation work focuses on using MRI to serially image rabbits undergoing the atherosclerotic protocol in order to assess rupture risk at the various time points. Previous work has determined that an increase in the vessel remodeling ratio (which hides a large plaque in the vessel wall) and contrast uptake (which indicates inflammation) are both characteristics of increased rupture risk. By obtaining these parameters at various time points in the disease progression, it was possible to determine when a certain plaque displays a heightened risk of rupture. The second portion of this work tested the efficacy of a pro-resolving molecule, lipoxin (an endogenous molecule), in reducing atherosclerotic disease state, specifically rupture with a luminal thrombus. Using chronic administration of this molecule in the same rabbit model of atherosclerosis yielded a faint reduction in atherosclerotic severity based on the parameters of decreased vessel lipid content and decreased thrombotic events presented in the treated group.

Stroke is one of the leading causes of death and disability worldwide with 20% of ischemic strokes attributed to carotid atherosclerosis. In recent years, morphological characteristics of atherosclerotic plaque such as a thin fibrous cap, large lipid-rich necrotic core, intraplaque haemorrhage and ulceration have shown correlations with subsequent clinical events. High resolution, multi-contrast magnetic resonance imaging (MRI) can qualitatively identify these features and monitor disease progression. Compared to traditional contrast weighted imaging, quantitative MRI could provide an objective assessment of disease. Therefore, the general hypothesis investigated in this thesis is: Quantitative MRI methods can be used to acquire objective biomarkers of carotid vessel wall and atherosclerotic plaque, with high accuracy and good repeatability. The research presented in this thesis describes the use of multiple quantitative MRI methods to evaluate the carotid vessel wall. These include dynamic contrast-enhanced (DCE) MRI analysis for the assessment of plaque inflammation/neovascularization and the development of black-blood quantitative T2/T2* mapping sequences for plaque component characterisation. The acceleration of the sequences was also investigated using a combination of compressed sensing (CS) and parallel imaging (PI). Chapter 3 investigated the hypothesis that plaque functional characteristics and surface morphology can be evaluated using a high temporal and spatial resolution 4D contrast-enhanced MRI/MR angiography (MRA) sequence. Chapter 4 tested the hypothesis that magnetisation prepared 3D fast-spin-echo (FSE) is the best sequence for in vivo T2 mapping. Four different black-blood T2 mapping sequences were developed and compared in phantom and volunteers. Chapter 5 tested the hypothesis that the optimised iMSDE 3D FSE T2 mapping sequence can be combined with CS and PI to further reduce the acquisition time without significantly affecting image quality and the measured T2 relaxation times. Chapter 6 investigated the hypothesis that compressed sensing can be used to reduce the overall examination time of a comprehensive multi-contrast MRI protocol, comprising black-blood T1 weighted, T2 weighted and proton density weighted sequences. Finally, Chapter 7 investigated the hypothesis that accurate 3D vessel wall R2* mapping can be achieved through black-blood preparation. In summary, this thesis investigated the use of multiple quantitative MRI methods in evaluating the carotid vessel wall and atherosclerotic plaque. The results demonstrate that quantitative MRI is an accurate and reproducible method for the carotid plaque characterization.

"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

The plastic deformation of stent during the implantation process, with considering the effect of artery and plaque, was investigated in this thesis. The stress-stretch relationships of porcine coronary arteries and aortas were obtained by the tensile test. The nonlinear ABAQUS finite element software was used in the analysis. The nonlinear-elastic, plastic and linear elastic material models for artery-plaque, stent and balloon were employed respectively. In this thesis, the initial folded balloon model was proposed to simulate the whole inflation and deflation process of balloon deformation. To investigate the effect of artery with plaque on the deformation of stent, the FEM model with considering the artery and plaque was proposed to simulate the expansion process of stents. The plaque¡¦s destruction during the expansion of stent was studied. The effects of plaque¡¦s thickness and the artery models on the expansion of stent were investigated. The effects of geometrical parameters and the influences on the deformation and the stress distribution of Palmaz type stent were discussed. The expansion ability and foreshortening of Chen and Tsai¡¦s stent were also assessed in this work. The results indicate that the limited expansion ability make Chen and Tsai¡¦s stent be not suitable for using as coronary stent. It might be used as the stent of carotid artery if its expansion ability improved by properly designing stent¡¦s diameter and geometry shape. The results reveal the foreshortening of Chen and Tsai¡¦s stent does not approach to zero as mentioned by Chen. A Chen modified and Tsai¡¦s stent was also proposed in this study. The simulation results show that the foreshortening in the Chen modified type is improved.

La thrombose est souvent liée à la survenue d’une rupture de la plaque d’athérosclérose qui expose le tissu sous endothélial thrombogène aux plaquettes sanguines circulantes. L’un des problèmes actuels est l’identification des mécanismes qui sont à l’origine de la fracture. Nous avons testé l’hypothèse que la vasoconstriction, induite par le LTC4 ou le thromboxane A2 (TXA2), joue un rôle dans la rupture de plaques d’athérosclérose et dans la formation de l’athérothrombose. Dans ce travail nous avons adapté la technique classique de la microscopie électronique pour observer les ruptures survenues sur une plaque d’athérosclérose. Avec cette méthode, nous avons montré qu’une vasoconstriction peut engendrer des ruptures de plaques, mais seulement lorsque ces plaques sont fragilisées (dites ‘vulnérables’) soit par un régime riche en graisse ou après exposition de la souris à un lipopolysaccharide extrait de membranes bactériennes. Nous avons montré aussi que la plaque produit du TXA2, et que l’absence de son récepteur chez les souris apoE-/- déficientes en TP prévient la rupture des plaques vulnérabilisées. La vasoconstriction constitue donc un élément déterminant dans la rupture des plaques vulnérables. Les résultats de ce travail identifient le TXA2 comme étant une éventuelle cible thérapeutique pour prévenir les ruptures des plaques. D’autre part, les analyses par microscopie électronique à balayage de la thrombose in vivo, et les analyses en microscopie électronique en transmission (MET) de l’ultrastructure des plaquettes agrégées in vitro, ont montré que les plaquettes activées fusionnent entre elle permettant ainsi la cicatrisation de l’endothélium lésé. / Rupture of atherosclerotic plaques exposes sub-endothelial thrombogenic material to circulating platelets, frequently leads to thrombus formation. At present, the mechanisms behind plaque ruptures are not well understood. We studied the hypothesis that vasoconstriction induced by LTC4 or thromboxane A2 (TXA2) plays an important role in plaque rupture and formation of atherothombosis. We used scanning electron microscopy to study rupture of the plaque in detail. We were able to show that vasoconstriction leads to plaque rupture, but only after plaques have been vulnerabilized by high fat diet, or by exposure of mice to lipopolysaccharide extracted from bacterial membranes. We could also show that plaques produce TXA2. As consequence the absence of TP, a receptor for TXA2 in apoE-/- mice prevented rupture of vulnerable plaques. Vasoconstriction is hence a determining factor in the rupture of vulnerable plaques. Our work has identified TXA2 as a potential therapeutic target in preventing plaque rupture. Moreover, analysis of the thrombosis in vivo by scanning electron microscopy, and the in vitro study of the ultra structure of aggregated platelets by transmission electron microscopy, showed that activated platelets fuse together to heal the injured endothelium.

This experiment compares the implications of two methods of measuring viral particles, specifically Influenza particles in human cell lines in vitro. These strategies include plaque assays and xCELLigence screening. Plaque assays, also known as reduction assays, are plates that are overlaid with semi-solid medium that limits the spread of the virus and shows where each particle is located based on the "plaque" or empty space on the plates where cells have died and been removed. xCELLigence screening is a newer program that checks for "impedance", an artificial number that will measure the cells killed by virus as well as cell to cell interaction on a 96 well plate that utilizes gold microelectrodes. Both methods have variables that can make them useful in certain situations, however, the focus is on how reliable the xCELLigence program is in comparison to more traditional methods of quantifying viral particles.