High resolution magnetic resonance imaging (MRI) is emerging as the most promising modality for direct plaque imaging. Direct plaque imaging has substantially advanced our understanding of the pathophysiology of acute coronary syndromes and cerebrovascular events. For example, direct plaque imaging has identified that acute coronary events frequently result from rupture of lipid rich plaque in areas of coronary atherosclerosis that are either invisible or insignificant on angiography. However, little is known about the clinical significance, pathophysiology, or natural history of lower extremity atherosclerotic plaque characteristics and their association with lower extremity outcomes in patients with lower extremity peripheral arterial disease (PAD). Our prior work demonstrates that patients with PAD have increased functional impairment and increased rates of functional decline compared to persons without PAD. In this proposed study, we will use MRI to identify specific characteristics of lower extremity atherosclerotic plaque and changes in plaque characteristics that are associated with functional decline in PAD. We will also identify associations between lower extremity collateral vessels with functional impairment and decline in PAD. We will assemble a cohort of 500 men and women with PAD and follow them prospectively for two years. At baseline and two year follow-up we will obtain consecutive cross-sectional MR images of the superficial femoral artery (SFA). Atherosclerotic plaque characteristics we will study are measures of plaque quantity (mean total arterial wall area, maximum arterial wall area) and measures of lumen reduction (maximum percent lumen reduction and average percent lumen reduction). The primary aims of this study are 1) to determine whether greater MRI-measured atherosclerotic plaque characteristics (i.e. greater plaque quantity and greater lumen reduction) are associated with greater functional impairment and decline in persons with PAD;2) to determine whether greater progression of MRI-measured atherosclerotic plaque characteristics are associated with greater functional decline in PAD;3) to identify associations between lower extremity collateral vessels with functional impairment and functional decline in persons with PAD. Substantive pilot data collected for this application demonstrate the validity and reliability of our proposed MRI measures, including measures of plaque quantity, percent lumen reduction, and collateral vessels. Results are expected to increase our understanding of the pathophysiology of lower extremity atherosclerosis and mechanisms of functional impairment and decline in persons with PAD. This knowledge, in subsequent studies, is expected to lead to new therapies for PAD-related functional impairment and functional decline.
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