? Rapid technological advances in magnetic resonance (MR) imaging in the last decade have yielded significant developments in our abilities to study experimental models of human disease. The investigators of this proposal are in the forefront of the study of small and large animal models of atherosclerosis and of human atherosclerosis, from the biological, clinical, and MR perspectives. We have pioneered the use of in vivo MR imaging for characterizing plaques in mouse models of human atherosclerosis. In a series of reports, we have established the strengths of MR to serially and non-invasively track lesional changes in experimental and human studies of atherosclerosis progression and regression. In this application, we propose to tackle the current limitations of this technique to detect lesions and to determine plaque size and composition in mouse models of atherosclerosis. We will use molecular MR imaging to target the pathophysiological processes within the plaque that could be critical to lesion instability. Our approach involves the design of a novel set of specific, targeted supramolecular contrast agents based on micelles (Aim 1) and well- developed techniques for reconstitution of high density lipoproteins (HDL) (Aim 2). These techniques will be further extended to deliver imaging agents into plaques based on the presence of specific molecules of interest (Aim 3). These studies will provide the basis for future advances in experimental studies of atherosclerogenesis and new clinical applications of non-invasive, in vivo MR imaging of atherosclerotic lesions. ? ? ?
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