DESCRIPTION (provided by applicant): Prosthetic heart valves (PHV) have been in use for over four decades to replace diseased heart valves. However, present-day designs are far from ideal and significant complications such as hemolysis, plateletdestruction, and thromboembolism often arise after their implantation, requiring aggressive life long anticoagulation therapy which in turn carries serious side effects. Improving current PHV designs, however, needs highly accurate flow quantification - a task not achievable until recently due to the complex and intricate geometries of PHVs combined with the lack of an appropriate computational methodology to tackle the complexities of PHV flows. Novel fluid-structure interaction CFD tools have been successfully developed and validated in the current grant. Along with numerous experimental studies, this numerical tool has yielded the first ever in depth understanding of the complex physics of PHV flows under physiological conditions and at hemodynamically relevant scales. The proposed competing renewal takes the next step towards achieving the development of a computational framework for improving valve prosthesis designs on a patient-specific basis. Current Magnetic Resonance Imaging (MRI) technology makes it possible to obtain full 3D moving geometries at resolution sufficiently high to prescribe aorta and ventricular wall motions as boundary conditions for the numerical model. By coupling high resolution CFD techniques with the latest advancements in MRI technology, a powerful and clinically useful hemodynamic/fluid dynamic analysis tool could be developed for the benefit of PHV recipients. The overall hypothesis driving this competing renewal is: High resolution, imaging-based Computational Fluid Dynamics (CFD) modeling can be used to develop viable patient-specific hemodynamic tools where cardiac devices (not only limited to heart valve prostheses) may be evaluated prior to patient treatment. This hypothesis will be addressed in the following four aims: Aim 1: Development of CFD tools for left ventricle/aorta configuration Aim 2: In vitro experiments for validation in a phantom left ventricle/aorta configuration with moving boundaries Aim 3: Develop image processing methods for reconstruction of anatomically accurate moving ventricle and aorta geometries Aim 4: Preliminary application of the computational tools for patient simulation and analysis Completion of this project will lead to a significant advancement in the field of heart valve flow analysis and the development of fluid mechanically improved cardiac devices. PUBLIC HEALTH RELEVANCE: Present day designs of prosthetic heart valves are far from ideal and significant risk of complications exist requiring patients to undergo aggressive life long anti-coagulation therapy which in turn carries additional risks. In this competing renewal, the computational technology produced during the original grant is further developed to be able to simulate flows in patient specific anatomies. This will be achieved by obtaining actual geometries of patients using magnetic resonance imaging and coupling this information with a more sophisticated and improved version of the current computational fluid dynamics software.

7. Project Narrative Present-day designs of prosthetic heart valves are far from ideal and significant risk of complications exist requiring patients to undergo aggressive life long anti-coagulation therapy which in turn carries additional risks. In this competing renewal, the computational technology produced during the original grant is further developed to be able to simulate flows in patient specific anatomies. This will be achieved by obtaining actualgeometries of patients using magnetic resonance imaging and coupling this information with a more sophisticated and improved version of the current computational fluid dynamics software.