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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BST-E (50))
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Larkin, Jennie E
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Yale University
Engineering (All Types)
Schools of Engineering
New Haven
United States
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Bhagavan, D; Di Achille, P; Humphrey, J D (2018) Strongly Coupled Morphological Features of Aortic Aneurysms Drive Intraluminal Thrombus. Sci Rep 8:13273
Rausch, Manuel K; Genet, Martin; Humphrey, Jay D (2017) An augmented iterative method for identifying a stress-free reference configuration in image-based biomechanical modeling. J Biomech 58:227-231
Wilson, John S; Bersi, Matthew R; Li, Guangxin et al. (2017) Correlation of Wall Microstructure and Heterogeneous Distributions of Strain in Evolving Murine Abdominal Aortic Aneurysms. Cardiovasc Eng Technol 8:193-204
Virag, Lana; Wilson, John S; Humphrey, Jay D et al. (2017) Potential biomechanical roles of risk factors in the evolution of thrombus-laden abdominal aortic aneurysms. Int J Numer Method Biomed Eng 33:
Jiao, Yang; Li, Guangxin; Korneva, Arina et al. (2017) Deficient Circumferential Growth Is the Primary Determinant of Aortic Obstruction Attributable to Partial Elastin Deficiency. Arterioscler Thromb Vasc Biol 37:930-941
Di Achille, P; Tellides, G; Humphrey, J D (2017) Hemodynamics-driven deposition of intraluminal thrombus in abdominal aortic aneurysms. Int J Numer Method Biomed Eng 33:
Phillips, Evan H; Di Achille, Paolo; Bersi, Matthew R et al. (2017) Multi-Modality Imaging Enables Detailed Hemodynamic Simulations in Dissecting Aneurysms in Mice. IEEE Trans Med Imaging 36:1297-1305
Jiao, Yang; Li, Guangxin; Li, Qingle et al. (2017) mTOR (Mechanistic Target of Rapamycin) Inhibition Decreases Mechanosignaling, Collagen Accumulation, and Stiffening of the Thoracic Aorta in Elastin-Deficient Mice. Arterioscler Thromb Vasc Biol 37:1657-1666
Bersi, M R; Khosravi, R; Wujciak, A J et al. (2017) Differential cell-matrix mechanoadaptations and inflammation drive regional propensities to aortic fibrosis, aneurysm or dissection in hypertension. J R Soc Interface 14:
Cyron, C J; Humphrey, J D (2017) Growth and Remodeling of Load-Bearing Biological Soft Tissues. Meccanica 52:645-664

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