Stroke is the third leading cause of mortality and the leading cause of disability in the United States. It is estimated that a significant fraction of all ischemic strokes are caused by carotid atherosclerotic disease. Often stroke is preceded by neurologic symptoms and may therefore be preventable with timely intervention. While the degree of arterial stenosis is a major risk factor, there are strong indications that factors unrelated to the size of the vascular construction play a role in causing neurologic symptoms. These include the extent of collateralization and the morphology and composition of the atheroscleotic plaque itself. Further, since most strokes are believed to be embolic in nature, reduced perfusion prevents clearance of microemboli forming distal to an unstable lesion. We hypothesize that in addition to plaque composition, hypoperfusion is an independent predictor of symptoms. In order to evaluate the above hypothesis the following specific aims will be pursued: 1. We will further develop and perfect the methodology developed in preliminary work for acquiring, processing and analyzing high-resolution MR images to measure plaque volume and architecture in vivo. 2. We shall implement and evaluate a multi-slice arterial spin labeling perfusion imaging technique for measuring perfusion in a single vascular distribution to unambiguously assess the implications of carotid stenosis on blood flow to the affected hemisphere. 3. Utilizing the methods developed in Aims 1 and 2 we shall, in a pilot study of symptomatic and asymptomatic patients (N=50 each) with clinically significant carotid stenosis (>70 percent), who will subsequently undergo carotid endarterectomy (CEA), determine the prevalence of hypoperfusion in each hemisphere in relation to luminal narrowing, plaque volume and composition. We shall then re-examine these patients post CEA with perfusion MRI to determine the extent of restoration of blood flow and evaluate the hypothesis that the perfusion deficit established prior to endarterectomy was related to carotid disease. We shall examine the CEA specimens by 13C NMR spectroscopy, micro-MRI and micro computed tomography to establish plaque's lipid profile and calcium content as a means to characterize the lesion and evaluate the association between plaque characteristics and patients' symptomatology.
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