NMR AND MR IMAGING STUDIES OF PLAQUE RUPTURE

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Although the advances have been made in the detection and treatment of vascular diseases, myocardial infarctions and strokes often strike apparently healthy persons without warning and produce disabilities or death. Atherosclerosis is the underlying cause of most heart attacks and strokes. Atherosclerotic plaques can grow slowly over time and gradually block blood flow, often producing symptoms that warn the patient of the underlying disease. However, less occlusive plaques can produce acute events within minutes by rupturing and abruptly forming an occlusive thrombus. These plaques appear to have certain physical characteristics, such as a thin fibrous cap and lipid-rich core, which distinguish them from less dangerous plaques. There is new urgency to evaluate vascular disease in humans by imaging methods that provide data about the ultrastructure of plaques, rather than invasive methods such as angiography that report only luminal narrowing. This project uses the modified Constantinides animal (rabbit) model of plaque rupture to compare plaque components and ultrastructure in non-ruptured and ruptured plaques. Magnetic resonance (MR) images of the aorta in rabbits (in vivo) will be obtained before and after triggering plaque rupture, and 9with higher resolution) after excision. Comparison of the MR images of ruptured and non-ruptured plaques will provide markers for plaque rupture and determine the value of MR imaging for predicting vulnerable plaques will provide markers for plaque rupture and determine the value of MR imaging for predicting vulnerable plaques in humans before rupture occurs. Magic angle spinning (MAS) NMR spectroscopy will be used to characterize in situ the composition of each lipid phase in excised plaques. MAS NMR allows quantitation of crystalline cholesterol, liquid and liquid-crystalline cholesteryl esters, and calcium salts in the intact plaque; each of these structures alone, or interactions between them, may play a role in plaque vulnerability. To enhance the interpretation of MR images, the detailed physical chemical information from MAS NMR will be integrated with the spatial information about lipid and protein components determined by magnetic resonance (MR) imaging and light microscopy/histology. Because the ultrastructure of plaques appears to be key to their stability and potential for regression, MR imaging has the potential for being a more reliable predictor of acute pathological events (heart attack and stroke).