The long-term objectives of this research are to understand (1) the role of hemodynamics in the genesis and development of atherosclerosis, and (2) the extent to which arterial geometry, as a mediator of the hemodynamic environment, influences an individual's susceptibility to vascular disease. The relationship between vascular geometry and vessel wall morphology will be examined for the proximal portion of the human left anterior descending coronary artery (LAD). Objective, computer-based algorithms will be implemented to reconstruct the three- dimensional axial geometry (i.e., the course of the vessel axes) of this segment; including the proximal portions of its early branches, from multiple post-mortem angiographic views of hearts collected and prepared by collaborating institutions under the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) protocols. The histology and morphometry of the radiographed specimens will be obtained at the University of Chicago and Ohio State University following the PDAY protocols. Quantitative geometric parameters of the segments (e.g., branch angles, branch asymmetry, distance between branch points and other landmarks, and tortuosity) will be found by applying objective algorithms to the three-dimensional axial geometries. The relation among these parameters, the morphology and pathology of the specimens, and the subjects' risk factor profiles (also specified by the PDAY procedures) will be examined in detail. This research will illuminate the role of hemodynamics in atherogensis, lending insights into the mechanisms by which the disease develops. An understanding of the relation between arterial geometry and the predisposition to atherosclerosis can improve the productivity of epidemiological studies and suggest """"""""geometric risk factors"""""""" that may predict an individual's susceptibility to atherosclerosis at specific sites.
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