Joel D. Morrisett, Ph.D.
Department of Medicine and Biochemistry & Molecular Biology
Scientific Director - Magnetic Resonance Microimaging & Spectroscopy Laboratory
Atherosclerotic lesions in the cardiovascular system range in severity from the limited fatty streak to the extensive complicated plaque. Between these extremes are lesions which are especially vulnerable to disruption at their surface, often leading to thrombosis and vessel occlusion. The non-invasive detection of these lesions in vivo provides valuable information for guiding appropriate medical and surgical intervention, as well as monitoring drug therapy over time. Our research involves integrated studies on the atherosclerotic lesions in human carotid arteries. A primary objective is to develop and refine in vivo MRI to a state where it can accurately quantify physical dimensions of carotid lesions at specific sites throughout the vessel. Data from image slices is used to generate 3D arterial profiles showing the volume, radial, position, and linear location of each plaque. A second objective is to develop in vivo MRI to a level where it can detect, discriminate among, and quantify specific chemical components of lesions (calcified, lipid-rich, fibrotic, necrotic, and thrombotic areas). 3D contour plots, parametric imaging, and feature space analysis are used to identify and measure these components. MRI images are calibrated by histologic and morphometric methods, using conventional and microarray tissue techniques. A third objective is to use laser capture microdissection (LCM) to isolate specific cell types (e.g. SMC, mφ, EC, osteoblast, osteoclast) and quantify constituent marker proteins associated with specific processes in carotid atherosclerosis (e.g. cell adhesion, cell proliferation, apoptosis, angiogenesis, proteolysis, calcification, lipid inclusion) and determine the effect of LDL-C lowering and HDL-C elevating drug therapy on them. A fourth objective is to localize and estimate the expression of genes controlling the synthesis of distinctive marker proteins in carotid lesion cells and determine the effect of lipid altering drugs on them by fluorescence in situ hybridization (FISH) and RNA expression profiling on DNA and oligonucleotide microarrays.