The overall goal of this project is to determine the change over time of parameters that are meaningful descriptors of atherosclerosis at the carotid bifurcation. Earlier studies of carotid disease have been hampered by imaging limitations. Non-invasive Magnetic Resonance Imaging (MRI) methods are now available that permit a three-dimensional evaluation of the geometric and compositional morphology of disease of the extracranial carotid arteries, a major source of stroke. These new methods permit an evaluation of both the flow lumen and the disease within the vessel wall. ? ? This study will examine, in patients with moderate to severe disease of the extracranial carotids, the changes over time in the cross-sectional area of the maximally stenosed lumen and in the heterogeneity of plaque composition. Imaging will be performed at baseline and one year later in 300 patients. A multi-center consortium has been formed to meet the goals of this project. By assembling this consortium, it will be possible to recruit the number of patients needed to answer the specific aims of the study with sufficient statistical power. Further, the multi-center composition of this study will provide results of greater generality than can be established by a single center. In addition to measuring changes in the primary descriptors of plaque, change over time of other descriptors (such as plaque bulk, plaque irregularity, or the volumes of specific plaque components) will be measured. Secondary aims of this application are to determine whether biochemical markers are correlated with plaque change, and whether semi-automated postprocessing tools can be used to efficiently analyze the MRI images of atherosclerotic disease. ? ? The results of this project will help define the number of subjects needed in a larger study aimed at determining which specific descriptors of 3-D morphology are most predictive of plaque progression, and would confirm that this consortium can attain that recruitment and retention goal. The larger study would provide an insight into mechanisms of plaque instability and would be helpful in achieving the long-term goal of identifying which imaging features are most sensitive in defining the neurological risk of carotid disease. Establishment of these imaging methods will also be valuable for drug trials aimed at determining the response of atherosclerosis to pharmacological interventions. ? ?
