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Mohammad Kaazempur Mofrad and Jeffrey Borenstein. Weinberg, Eli, 1979- Massachusetts Institute of Technology. Dept. of Mechanical Engineering. Massachusetts Institute of Technology. Department of Mechanical Engineering 2009-03-16T19:44:25Z 2009-03-16T19:44:25Z 2008 2008 http://hdl.handle.net/1721.1/44797 300450854 Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2008. Includes bibliographical references (p. 136-148). This thesis presents mathematical models describing the mechanical behavior of the human aortic heart valve over a range of length and time scales. In the human heart, the valves perform the vital function of controlling the direction of blood flow. Each valve is an intricate mechanical structure, with distinct features and functions at multiple scales. This effort first develops a framework of reference configurations that enables communication between simulations of the different length scales. Three simulations are created within that framework. At the cell scale, the interaction between a single valvular interstitial cell and its surrounding matrix is described. At the tissue scale, a model is created for the valve cusp tissue mechanical behavior, including the multilayered, nonuniform geometry and nonlinear, anisotropic material properties. At the organ scale, a dynamic, three-dimensional model with fluid-structure interaction predicts the motion of the valve, blood, and surrounding tissue. Each simulation is verified against a number of experimental measures. These three simulations together constitute a model for the dynamic, three-dimensional, multiscale mechanical behavior of the healthy human aortic heart valve throughout the cardiac cycle. The model is employed to perform multiscale investigation into the mechanisms of the disease calcific aortic stenosis in three ways. First, the model of the healthy valve is extended to describe disease progression on the decade time scale. Calcification is introduced at the tissue level and the effects on valve function are monitored at the organ level. Second, the role of mechanical deformations in the disease process is examined by comparing multiscale deformations between the normal valve case and a known disease-prone case. (cont.) Finally, a combined computational and experimental study investigates the role of fluid shear in calcific disease. Shears computed in the organ-scale simulation are applied to endothelial cells in vitro. The cells express disease-related genes in a manner consistent with the region-specific nature of calcific disease, providing evidence for a role of shear in the disease process. The multiscale model presented in this thesis has further utility in investigating function, disease, and therapy of the human aortic valve. by Eli J. Weinberg. Ph.D. 148 p. eng Massachusetts Institute of Technology M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 Mechanical Engineering. Multiscale simulations of the aortic heart valve : applications in disease and surgery Thesis application/pdf Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="d89931cc-e0c8-4d15-b9fe-af9bd68470c9"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>Multiscale simulations of the aortic heart valve : applications in disease and surgery</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2008</PublicationDate> <Authors> <Author> <DisplayName>Weinberg, Eli, 1979-</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Mechanical Engineering.</Keyword> <Abstract>This thesis presents mathematical models describing the mechanical behavior of the human aortic heart valve over a range of length and time scales. In the human heart, the valves perform the vital function of controlling the direction of blood flow. Each valve is an intricate mechanical structure, with distinct features and functions at multiple scales. This effort first develops a framework of reference configurations that enables communication between simulations of the different length scales. Three simulations are created within that framework. At the cell scale, the interaction between a single valvular interstitial cell and its surrounding matrix is described. At the tissue scale, a model is created for the valve cusp tissue mechanical behavior, including the multilayered, nonuniform geometry and nonlinear, anisotropic material properties. At the organ scale, a dynamic, three-dimensional model with fluid-structure interaction predicts the motion of the valve, blood, and surrounding tissue. Each simulation is verified against a number of experimental measures. These three simulations together constitute a model for the dynamic, three-dimensional, multiscale mechanical behavior of the healthy human aortic heart valve throughout the cardiac cycle. The model is employed to perform multiscale investigation into the mechanisms of the disease calcific aortic stenosis in three ways. First, the model of the healthy valve is extended to describe disease progression on the decade time scale. Calcification is introduced at the tissue level and the effects on valve function are monitored at the organ level. Second, the role of mechanical deformations in the disease process is examined by comparing multiscale deformations between the normal valve case and a known disease-prone case.</Abstract> <Abstract>(cont.) Finally, a combined computational and experimental study investigates the role of fluid shear in calcific disease. Shears computed in the organ-scale simulation are applied to endothelial cells in vitro. The cells express disease-related genes in a manner consistent with the region-specific nature of calcific disease, providing evidence for a role of shear in the disease process. The multiscale model presented in this thesis has further utility in investigating function, disease, and therapy of the human aortic valve.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>