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

开发心血管疾病生长的计算机模型需要一个器官尺度的血流模型，一个细胞尺度的细胞生物学模型，以及一个将这些模型耦合起来的框架。这样的计算机模型可以通过模拟疾病生长的时空模式来帮助预测心血管疾病。为了开发这些模型，我们需要一个集成了来自多个学科的建模技术的软件基础设施。本项目将为此目的开发软件，并将该软件应用于老年人普遍存在的钙化主动脉瓣病（CAVD）问题。该项目还将有助于了解CAVD中涉及的基本生物和机械过程之间的相互作用。该项目利用北亚利桑那大学的现有资源，针对该地区代表性不足的少数民族学生开展外展活动。这项研究的结果将有助于促进国民健康，并提高我们对心血管疾病不同过程之间相互作用的科学认识。在过去的二十年中，心血管疾病的器官尺度患者特异性计算模型的发展取得了重大进展。这些模型通常关注特定的空间和时间尺度，其目标是量化心血管疾病生长的生物力学生物标志物。然而，在这些模型中缺少关于长时间尺度疾病生长的定量信息。本项目的目标是1)开发一个用于器官尺度生物力学和细胞尺度系统生物学模型之间多尺度双向耦合的软件平台。2)应用计算框架研究CAVD的长期时空演变。器官尺度模型将基于连续固体和流体力学模型，而细胞尺度模型将基于微分方程系统。开发的软件基础设施可以应用于患者特定数据，以模拟疾病进展模式。这将使变革性模型的发展成为可能，从而提高我们对心血管疾病的认识。该项目将在软件开发、生物力学和生物学的界面培养高度跨学科的研究人员。外展活动将通过展示计算机科学和工程融合并应用于生物医学应用的美丽来促进STEM的参与。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.