The overall goal of this study is to elucidate the pathophysiology that underlies the development and composition of atherosclerosis by analyzing gadolinium-based contrast-enhanced MRI (CE-MRI) features of atheroma of the carotid artery. In particular, we are interested in atherosclerosis in its earliest stage, at a lime when medical intervention is critical. Early atheroma formation and the relationships of its components to surrogate markers of disease are poorly understood. CE-MRI offers a direct assessment of atherosclerotic changes within the vessel wall that can be related to serologic measures of disease. We will conduct this study within the framework of the Multi-Ethnic Study of Atherosclerosis (MESA), an NHLBI-funded, prospective study of subclinical atherosclerosis in 6,500 subjects without clinically manifest atherosclerotic disease. A primary objective of MESA is to determine what factors influence the progression of mild subclinical atherosclerosis to more severe subclinical disease. The extensive database and infrastructure offered by MESA provides the ideal environment for this analysis. Our preliminary studies have shown the unique ability of CE-MRI to characterize atherosclerotic changes in the wall of the carotid artery, both at early and advanced stages. Our data indicate that CE-MRI is capable of detecting atherosclerosis even before overt wall thickening develops, and that it can discriminate the morphologic components of atheroma. By linking imaging to serology, we will assess the significance of otherwise nonspecific abnormalities in relationship to structural findings of CE-MRI. In this regard, we will develop a greater understanding of the earliest features of atheroma formation and the clinical implications of its components in order to reduce the development of atherosclerotic disease and its attendant risks, particularly stroke. The results of this study may form the basis of a larger longitudinal evaluation of the progression of atherosclerosis as it relates to underlying cardiovascular risk factors and medical intervention, possible only with this noninvasive technique.