CRII: OAC: A computational framework for multiscale simulation of cardiovascular disease progression connecting cell-scale biology to organ-scale hemodynamics

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Developing computer models of cardiovascular disease growth requires an organ-scale model of blood flow, a cell-scale model of cell biology, and a framework to couple these models. Such computer models could help predict cardiovascular disease by simulating spatial and temporal patterns of disease growth. To develop these models, we need a software infrastructure that integrates modeling techniques from multiple disciplines. This project will develop software for this purpose and will apply the software to the calcific aortic valve disease (CAVD) problem, which is prevalent in aging adults. The project will also help to understand the interaction between the fundamental biological and mechanical processes involved in CAVD. The project leverages existing resources at Northern Arizona University to perform outreach activities targeting underrepresented minority students in the region. The outcome of this study will contribute to advancing the national health and improving our scientific understanding of the interaction between different processes in cardiovascular disease. During the past two decades, significant advances have been made in the development of organ-scale patient-specific computational models of cardiovascular disease. These models often focus on a specific spatial and temporal scale and their goal is to quantify biomechanical biomarkers of cardiovascular disease growth. However, quantitative information about disease growth over long time scales is missing in these models. The goal of this project is to 1) Develop a software platform for multiscale two-way coupling between organ-scale biomechanics and cell-scale systems biology models. 2) Apply the computational framework to study the long-term spatial and temporal progression of CAVD. The organ-scale model will be based on continuum solid and fluid mechanics models, and the cell-scale model will be based on systems of differential equations. The developed software infrastructure could be applied to patient-specific data to model disease progression patterns. This will enable the development of transformative models that advance our knowledge of cardiovascular disease. The project will train highly interdisciplinary researchers at the interface of software development, biomechanics, and biology. Outreach activities will promote STEM participation by demonstrating the beauty of computer science and engineering blended and applied to biomedical applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.