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

开发心血管疾病增长的计算机模型需要器官规模的血液流动模型、细胞规模的细胞生物学模型以及将这些模型结合在一起的框架。这样的计算机模型可以通过模拟疾病增长的空间和时间模式来帮助预测心血管疾病。要开发这些模型，我们需要一个集成了多个学科的建模技术的软件基础设施。该项目将为此目的开发软件，并将该软件应用于钙化性主动脉瓣疾病(CAVD)问题，该问题在老年人中很常见。该项目还将有助于了解CAVD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族裔学生开展外联活动。这项研究的结果将有助于促进国民健康，提高我们对心血管疾病不同过程之间相互作用的科学理解。在过去的二十年里，在心血管疾病的器官尺度的患者特定的计算模型的开发方面取得了重大进展。这些模型通常集中在特定的空间和时间尺度上，它们的目标是量化心血管疾病增长的生物力学生物标志物。然而，在这些模型中，缺乏关于疾病在长时间尺度上增长的定量信息。本项目的目标是1)开发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。器官尺度的模型将基于连续的固体和流体力学模型，细胞尺度的模型将基于微分方程组。开发的软件基础设施可以应用于患者特定的数据，以模拟疾病进展模式。这将使我们能够开发出促进我们对心血管疾病了解的变革性模型。该项目将在软件开发、生物力学和生物学方面培训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NSF的法定使命，并通过使用基金会的智力优势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.