Magnetic resonance imaging (MRI) is a proven technique that can non-invasively identify key pathological features of carotid atherosclerosis. Prior MRI studies have shown that carotid intraplaque hemorrhage (IPH) and lumen surface disruption are associated with increased risk for future ischemic events, and that IPH is associated with more rapid plaque progression and presence of greater inflammatory activity and neovascularization. In our current cohort study, we tested the hypothesis that despite statin therapy and aggressive regulation of blood pressure, stability of carotid lesions with IPH is compromised. Findings to date support our original hypothesis. Further, preliminary interim analysis of our data suggest potential risk factors and MRI signal characteristics that are associated with the progression of IPH. However, longer-term follow-up is critical to confirm these promising initial findings. The central hypotheses of this competing renewal are that i) hemodynamic factors and increased plaque neovascularization are associated with the development of new or repeated IPH, and ii) the rate of plaque progression is driven by repeated IPH that can be characterized by MR T1 and T2 mapping -- a quantitative means to assess IPH resolution and recurrence. The long-term goals of our research is to utilize MRI in prospective clinical studies to gain insight into the pathogenesis of the high-risk carotid plaque, to identify risk factors associated with more rapid progression, and ultimately, to establish carotid plaque imaging as a clinical diagnostic tool for reduction of incident stroke. Globally, stroke remains one of the leading causes of serious long-term disability and mortality and carotid atherosclerosis is a significant contributor. A better understanding of its pathogenesis is critically needed to develop more effective methods for primary and secondary stroke prevention.

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Globally, stroke remains one of the leading causes of serious long-term disability and mortality and carotid atherosclerosis is a significant contributor. This proposal seeks to investigate the role of intraplaque hemorrhage in the pathogenesis of the high-risk carotid artery plaque and to identify risk factors associated with more rapid disease progression. We aim to achieve these goals by developing quantitative magnetic resonance imaging techniques and by applying those tools in a prospective cohort study of intensively monitored study participants. A better understanding of the pathogenesis of high risk carotid plaque is critically needed to develop more effective methods for primary and secondary stroke prevention.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Medical Imaging Study Section (MEDI)
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Fleg, Jerome L
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University of Washington
Schools of Medicine
United States
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