Abdominal aortic aneurysms (AAAs) are most common in men aged 65 and older, thus the incidence of this disease is on the rise in our aging population. It is universally agreed that mechanical factors play key roles in the natural history of AAAs and their response to treatment, yet there is no widely accepted tool to quantify or predict the mechanobiology and biomechanics of AAAs. Our overall goal is to support and extend the Cardio- vascular Fluid Dynamics Project at the Symbios National Center for Biomedical Computing at Stanford University by (1) developing novel constitutive relations that describe complex chemo-mechanical changes experienced by the abdominal aorta during the progression of aneurysmal disease, (2) implementing these relations in a custom nonlinear finite element code developed for diseased arteries, (3) interfacing this arterial mechanics code with the Stanford biofluid mechanics code to enable us to quantify, for the first time, the fluid- solid-growth mechanics of a growing AAA, and (4) using parametric studies as well as data available at Stanford and Pittsburgh from patients to refine and verify the predictive capability of this unique computational tool. Finally, the Stanford Center will ensure that the combined software packages will be portable, easily used, and widely available. Toward this end, we bring together expertise from 3 additional institutions: J. Humphrey, at Texas A&M University, has expertise in developing complex constitutive theories for soft tissues, including growth and remodeling of arteries and cerebral aneurysms;D. Vorp, at the University of Pittsburgh, has expertise in quantifying biomechanical properties of abdominal aortic aneurysms and associated intraluminal thrombi, and has performed numerous simulations of aneurysmal wall stress;and G. Holzapfel, at Graz University of Technology in Austria, has expertise in computational biosolid mechanics, particularly using finite elements to model complex atherosclerotic arteries and arterial-balloon-stent interactions. Together, these three groups represent the expertise needed to complement that at Stanford University: C. Taylor, with expertise in computational biofluid mechanics, and C. Zarins, with expertise in vascular surgery and animal models of disease progression. Together, we will develop the first computational tool that is designed to predict the natural history and responses to intervention of abdominal aortic aneurysms, the 13th leading cause of death in the U.S.A. Ruptured abdominal aortic aneurysms account for 15,000 deaths per year in the U.S.A. alone, thus representing the 13th leading cause of death. It is well known that mechanical factors play key roles in the progression and eventual rupture of these lesions (e.g., rupture occurs when wall stress exceeds strength), yet there is currently no way to understand simultaneously the evolving changes in blood flow dynamics, wall mechanics, and microstructure that govern the biomechanics of aneurysms. This research proposal is in response to PAR-07-249: it will both address the need to build a unique, comprehensive, computational tool to understand better the natural history of aneurysms and significantly extend the cardiovascular research capabilities at the Stanford University National Center for Biomedical Computing.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL086418-05
Application #
8213389
Study Section
Special Emphasis Panel (ZRG1-BST-E (50))
Program Officer
Larkin, Jennie E
Project Start
2008-04-01
Project End
2013-03-31
Budget Start
2011-12-01
Budget End
2013-03-31
Support Year
5
Fiscal Year
2012
Total Cost
$486,322
Indirect Cost
$85,303
Name
Yale University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Di Achille, P; Tellides, G; Humphrey, J D (2016) Hemodynamics-driven deposition of intraluminal thrombus in abdominal aortic aneurysms. Int J Numer Method Biomed Eng :
Bersi, Matthew R; Bellini, Chiara; Di Achille, Paolo et al. (2016) Novel Methodology for Characterizing Regional Variations in the Material Properties of Murine Aortas. J Biomech Eng 138:
Rausch, M K; Karniadakis, G E; Humphrey, J D (2016) Modeling Soft Tissue Damage and Failure Using a Combined Particle/Continuum Approach. Biomech Model Mechanobiol :
Rausch, Manuel K; Humphrey, Jay D (2015) A microstructurally inspired damage model for early venous thrombus. J Mech Behav Biomed Mater 55:12-20
Rao, Jayashree; Brown, Bryan N; Weinbaum, Justin S et al. (2015) Distinct macrophage phenotype and collagen organization within the intraluminal thrombus of abdominal aortic aneurysm. J Vasc Surg 62:585-93
Virag, Lana; Wilson, John S; Humphrey, Jay D et al. (2015) A Computational Model of Biochemomechanical Effects of Intraluminal Thrombus on the Enlargement of Abdominal Aortic Aneurysms. Ann Biomed Eng 43:2852-67
Lee, Y-U; Lee, A Y; Humphrey, J D et al. (2015) Histological and biomechanical changes in a mouse model of venous thrombus remodeling. Biorheology 52:235-45
Roccabianca, S; Figueroa, C A; Tellides, G et al. (2014) Quantification of regional differences in aortic stiffness in the aging human. J Mech Behav Biomed Mater 29:618-34
Blose, Kory J; Ennis, Terri L; Arif, Batool et al. (2014) Periadventitial adipose-derived stem cell treatment halts elastase-induced abdominal aortic aneurysm progression. Regen Med 9:733-41
Cyron, C J; Wilson, J S; Humphrey, J D (2014) Mechanobiological stability: a new paradigm to understand the enlargement of aneurysms? J R Soc Interface 11:20140680

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