The Woodruff School

SUMMARY

Thrombosis formation upon rupture or erosion of an atherosclerotic plaque can lead to occlusion of arteries. Arterial thrombosis is the most common final event in the cause of acute coronary syndrome and stroke. Thrombosis formation requires rapid platelet accumulation rates exceeding thrombosis lysis and embolization rates. Hemodynamics greatly affects platelet accumulation rate through affecting both platelet transport rate and platelet binding at thrombotic sites. For example, the presence of red blood cells (RBCs) in blood increases platelet transport rate by several orders of magnitude compared to transport due to Brownian motion. The lateral migration of platelets towards the vessel walls also results high platelet concentration at the RBC-depleted layer. In addition, platelet dynamics at this region may affect the rate of adhesion of platelets to the site of damage by changing collision frequency rate, collision contact time and available area in contact. The overall purpose of this study is to prevent thrombosis through hemodynamic mechanisms. First, important hemodynamic parameters controlling platelet transport and platelet dynamics at RBC-depleted layer will be determined by performing simulations using a coarse-grained spectrin-link method for RBC membranes and Newtonian dynamics for rigid particles coupled with a 3D lattice-Boltzmann fluid solver using standard bounce-back boundary conditions. This model provides a tool to directly simulate RBC and platelet mechanics and particle-particle and particle-fluid interactions in blood flow. Next, in vitro experiments will be performed to validate results obtained from the numerical studies: Axial concentration profiles of platelet-sized fluorescent microparticles in rectangular microcapillaries will be measured to investigate the effects of hemodynamical parameters found critical in margination process such as platelet shape and RBC mechanical properties on margination. Finally, the understanding of underlying hemodynamical mechanisms controlling platelet transport and adhesion will be used to develop methods for preventing thrombosis formation. This last objective can be performed by designing stents to change the upstream hemodynamics of the blood flow.

SUBJECT:	Ph.D. Proposal Presentation

BY:	Marmar Mehrabadi

TIME:	Monday, April 30, 2012, 9:30 a.m.

PLACE:	IBB Building, 1128

TITLE:	Reduction of Near-Wall Platelet Concentration in Arterial Stenoses through Hemodynamic Mechanisms

COMMITTEE:	Dr. David Ku, Co-Chair (ME) Dr. Cyrus Aidun, Co-Chair (ME) Dr. Mostafa Ghiaasiaan (ME) Dr. Julie Champion (ChBE) Dr. Kenichi Tanaka (Emory University)

SUMMARY Thrombosis formation upon rupture or erosion of an atherosclerotic plaque can lead to occlusion of arteries. Arterial thrombosis is the most common final event in the cause of acute coronary syndrome and stroke. Thrombosis formation requires rapid platelet accumulation rates exceeding thrombosis lysis and embolization rates. Hemodynamics greatly affects platelet accumulation rate through affecting both platelet transport rate and platelet binding at thrombotic sites. For example, the presence of red blood cells (RBCs) in blood increases platelet transport rate by several orders of magnitude compared to transport due to Brownian motion. The lateral migration of platelets towards the vessel walls also results high platelet concentration at the RBC-depleted layer. In addition, platelet dynamics at this region may affect the rate of adhesion of platelets to the site of damage by changing collision frequency rate, collision contact time and available area in contact. The overall purpose of this study is to prevent thrombosis through hemodynamic mechanisms. First, important hemodynamic parameters controlling platelet transport and platelet dynamics at RBC-depleted layer will be determined by performing simulations using a coarse-grained spectrin-link method for RBC membranes and Newtonian dynamics for rigid particles coupled with a 3D lattice-Boltzmann fluid solver using standard bounce-back boundary conditions. This model provides a tool to directly simulate RBC and platelet mechanics and particle-particle and particle-fluid interactions in blood flow. Next, in vitro experiments will be performed to validate results obtained from the numerical studies: Axial concentration profiles of platelet-sized fluorescent microparticles in rectangular microcapillaries will be measured to investigate the effects of hemodynamical parameters found critical in margination process such as platelet shape and RBC mechanical properties on margination. Finally, the understanding of underlying hemodynamical mechanisms controlling platelet transport and adhesion will be used to develop methods for preventing thrombosis formation. This last objective can be performed by designing stents to change the upstream hemodynamics of the blood flow.