Thrombosis following disrupture or superficial erosion of an atherosclerotic plaque is the most frequent underlying cause of acute coronary syndromes, cerebrovascular events, and peripheral vascular events. Disrupted or eroded plaques either progress to occlusive thrombosis, heal (organize), or lead to recurrent thrombosis. Healing or aging involves lysis of at least part of the thrombus followed by smooth-muscle cell proliferation and production of collagen. A residual thrombus increases the risk of recurrent thrombosis. One of the main factors in recurrent thrombosis is the thrombogenicity of the residual thrombus. It is now recognized that the magnitude and extent of the dynamic thrombus in the lumen explain the ischemic insults that result in the clinical syndromes. Atherothrombotic plaques have not been reliably detected by current diagnostic techniques. Recently, much research has been directed to the use of high-resolution multi-contrast weighted MRI for the detection of lipid-rich atherosclerotic plaques. The immediate goal of our proposal is to expand the noninvasive MRI-based measurements of plaque features for the study, of thrombus/intraplaque hemorrhage (IH), thrombus/IH thrombogenicity, and the detection of atherothrombotic plaques. The overall goal of this project is to use in vivo noninvasive MRI to accurately assess the propensity of an atherothrombotic plaque to initiate arterial thrombosis and lead to an ischemic event by virtue of its structural, chemical, and molecular composition. Specifically: 1) We will further develop and validate new and improved hardware and software methodologies for detecting and characterizing thrombosis and atherothrombotic carotid arteries plaques using in vivo high- resolution (using """"""""natural"""""""" non-contrast enhanced MR and using a targeted MR contrast agent for molecular imaging of fibrin; 2) We will use the improved high-resolution MR methods to detect and characterize in an in vivo experimental porcine model the structure and activity of thrombus in the various stages of """"""""aging"""""""" and correlate the MR-based findings with histopathology, and thrombogenicity; 3) As in 2), we will identify and characterize atherosclerotic plaque, thrombus, and IH in patients with symptomatic and asymptomatic carotid artery disease using in vivo high-resolution MRI.
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