Monocytes play a central role in the events that lead to a vulnerable atherosclerotic lesion. The first step in this process, monocyte adhesion, is known to be shear stress dependent through a combination of physical and biological factors. One consequence of the subsequent inflammatory response is local enzymatic degradation that can potentially weaken the plaque and make it more susceptible to fissure from the mechanical stresses associated with arterial blood pressure. Progression of the atherosclerotic lesion to rupture is therefore strongly influenced by a combination of mechanical and fluid dynamic factors. These factors relate to the distributions of shear stress acting on the endothelium and tissue-borne strains experienced by the endothelium and monocytes/macrophages. One objective of this proposal is to gain a better appreciation of these stresses and strains, their magnitude and distribution, through realistic numerical simulation of blood flow and vessel wall deformation. A second objective is to use these numerical results, in conjunction with histological measurements and MR imaging, to establish relationships between the hemodynamics and vessel wall deformation on one hand, and monocyte adhesion/invasion and plaque deterioration on the other. The realism of these calculations will rely upon detailed anatomical and compositional data obtained by MR imaging. The hypotheses listed below will be tested by comparing predictions of numerical simulations to histologic examination of the tissue.
Specific Aim 1. Use MR imaging of vessel anatomy, composition, and velocity profile combined with computational methods of fluid and solid analysis to generate a realistic simulation of flow and deformation in the vicinity of an atherosclerotic lesion.
Specific Aim 2. To test the hypothesis that locations on the lumenal surface exposed to low fluid dynamic shear stress correlate with regions of inflammation and tissue degradation.
Specific Aim 3. To test the hypothesis that sites of inflammation/degradation correlate with regions within the tissue that experience high mechanical strain.
