The primary objective of this work is to develop a quantitative method for the assessment of atherosclerosis that can noninvasively detect and quantify the disease in its early stages, before the vessel is occluded or severely stenotic. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) are effective for imaging vessels with advanced atherosclerotic disease.The focus of this work is on the development and evaluation of a new MRI technique that can directly image the subintimal lipid deposits of atherosclerotic disease. Lipid deposits, primarily cholesteryl esters, are characteristic of early stage atherosclerosis, and the amount of these lipids can potentially provide a quantitative measure of disease. The new MRI method is based on a stimulated-echo diffusion-weighted (STED) sequence that suppresses water and allows direct visualization of the less mobile lipids.
The research aims to: (1) optimize and improve the sequence for lipid imaging, (2) demonstrate that accurate quantitation of the lipid accumulation is possible, (3) show that detection and quantitation of the lipid is possible in an in-vivo animal model, and (4) develop the technique on a whole-body imaging system. Investigation of the properties of the water signal will complement the work on the tissue lipids. One of the main tasks will be to investigate several improvements to the basic technique to make it less sensitive to the effects of non- random motion, and then to optimize the timing of the technique based on accurate knowledge of the physical properties of the tissue water and the lipid. In-vivo imaging will be demonstrated in an animal model of atherosclerosis. Evaluation of the quantitative accuracy and sensitivity of the imaging method will be accomplished using phantoms, excised human tissue samples, and the rabbit model. The final component of the research will be to implement the technique on a clinical whole- body imaging system. This will require construction of a special- purpose gradient coil to provide a higher diffusion gradient field than is available on conventional MRI systems. The result of this research will be the development of an accurate noninvasive method for quantitative evaluation of atherosclerosis. Such a method would be useful both as a general-purpose diagnostic test and as a tool for studying the factors that influence disease progression and regression in animal models and in man.
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