PhD Proposal by Christian Rivera

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Christian Rivera

Ph.D. Proposal Presentation


Date: Monday August 22nd, 2016

Time: 2:30 PM

Location: EBB 1005


Committee Members:

Manu O. Platt, PhD (Gatech Advisor)

Yunlong Huo, PhD (PKU Advisor)

Alessandro Veneziani, PhD

Edward A. Botchwey, PhD

Wilbur A. Lam, MD, PhD

Tequila A. L. Harris. PhD



The Role of Geometry on the Hemodynamics and Biomechanics Associated with Accelerated Stroke Development in Sickle Cell Anemia

Children and adolescents with sickle cell anemia (SCA) have a high incidence of stroke with 11.5% of individuals developing an overt stroke before 18 years of age, and those between 2 and 8 at the greatest risk. Elevated mean velocities in the cerebrovasculature exceeding 200 cm/s is a strong indicator of stroke risk in SCA with 50% of individuals developing a stroke within 3 years after being diagnosed with high cerebral velocities. Cerebral angiograms have shown stenoses to occur in large artery vessels, specifically in the distal internal carotid artery (ICA) and the middle cerebral artery (MCA). Autopsies of patients with the disease have shown remarkable vascular remodeling characterized by intimal hyperplasia and luminal narrowing, but it is unclear how such accelerated remodeling is occurring in children with SCA. A group of proteolytic enzymes, known as cathepsins play a key factor in the vascular remodeling process. The powerful human elastase, cathepsin K, is upregulated in the endothelial cells of subjects affected by SCA; and may lead to accelerated matrix degradation that stimulates neointimal proliferation. Increased adhesion of blood cells, including leukocytes and erythrocytes, to the endothelium in individuals with SCA, may also cause additional luminal narrowing. The formation of stenoses through these mechanisms can alter the hemodynamic profiles in the artery; producing the high blood velocities indicative of stroke risk and regions of disturb flow that can stimulate further cellular remodeling. Therefore, analyzing the relationship between the geometry and hemodynamics is crucial to understanding the biomechanical mechanisms causing accelerated stroke development in SCA. In order analyze the mechanisms that may lead to stroke in SCA, a combination of both in vitro and in silico studies will be used to investigate the hemodynamics of the cerebrovasculature. The objective of this proposal is to identify and validate flow-mediated mechanisms of accelerated cerebrovascular remodeling predisposing children with sickle cell anemia to strokes. Therefore, the central hypothesis of this proposal is that the pathophysiology in sickle cell disease including inflammation and increased cellular adhesions produces hemodynamic profiles which can stimulate cathepsin expression and intimal hyperplasia leading to vascular changes that cause accelerated progression of stroke in sickle cell anemia.


  • Workflow Status: Published
  • Created By: Tatianna Richardson
  • Created: 08/10/2016
  • Modified By: Fletcher Moore
  • Modified: 10/07/2016


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