CAREER: A Parallel Computational Framework of Multiscale Geometric Modeling and Mesh Generation for Cardiac Biomechanics Application

这个CAREER项目的总体目标是建立一个新的多尺度几何建模和网格生成的并行计算框架，可以应用于心脏生物力学应用。这种能力将能够准确、稳定、高效地模拟许多生物过程，如钙（Ca2+）介导的信号传导、兴奋-收缩耦合和心肌细胞的能量代谢，并导致心脏生物力学的巨大进步。在心肌细胞中，Ca2+以其在收缩激活中的作用而闻名。Ca2+分布的改变现在被认为是心功能障碍的主要机制，包括心律失常和肥厚。为了预测和分析Ca2+动力学和心脏兴奋-收缩耦合是如何调节的，需要对大而复杂的t小管网络和相关蛋白复合物的实际几何形状进行建模。然而，以前的研究仅限于简化的几何形状。在这个项目中，PI的重点是：1)从蛋白质数据库中的原子分辨率数据开始，对蛋白质复合物进行多尺度几何建模；2)解决拓扑模糊，提高曲率驱动质量的并行网格生成；3)具有复杂现实几何结构的心室肌细胞Ca2+信号的自适应有限元分析模型验证。为了处理如此庞大、复杂的系统，将开发多核并行网格工具包并将其封装在仿真软件中。所提出的研究将在模型开发和仿真中达到最高的精度、效率和鲁棒性。它将显著提高心脏应用的预测能力，以及对分子和细胞尺度上解剖和生理特性的理解。这种并行计算基础设施也可用于其他复杂系统，为工程师和科学家提供了构建精确计算机模型的新技术。此外，这个跨学科项目将通过新的教育工具和课程开发以及外展活动将研究和教育结合起来。学生将与合作机构互动，以获得实际问题的第一手经验。妇女、少数民族和高中生将通过CMU的K-12课程参与拟议的研究和教育活动。教育活动将与CMU的Eberly卓越教学中心一起进行评估。

The overall goal of this CAREER project is to establish a novel parallel computational framework of multiscale geometric modeling and mesh generation that can be applied to cardiac biomechanics applications. This capability will enable accurate, stable, efficient simulations of many biological processes such as calcium (Ca2+) mediated signaling, excitation-contraction coupling and energy metabolism in cardiac muscle cells, and lead to great advances in cardiac biomechanics. In cardiac muscle cells, Ca2+ is best known for its role in contraction activation. Alterations in Ca2+ distributions are now recognized to be the primary mechanisms of cardiac dysfunction in a diverse range of common pathologies including cardiac arrhythmias and hypertrophy. To predict and analyze how Ca2+ dynamics and cardiac excitation-contraction coupling are regulated, modeling of realistic geometries of large, complicated t-tubule network and associated protein complexes is needed. However, previous studies have been limited to simplified geometries. In this project, the PI focuses on 1) multiscale geometric modeling for protein complexes starting from atomic resolution data in the Protein Data Bank; 2) parallel mesh generation with topology ambiguity resolved and curvature-driven quality improvement; and 3) model validation in adaptive finite element analysis of Ca2+ signaling in ventricular myocytes with complicated realistic geometry. To handle such large, complicated systems, multicore parallel meshing toolkits will be developed and encapsulated with the simulation software. The proposed research will attain the highest degree of accuracy, efficiency and robustness in model development and simulation. It will significantly advance predictive capability in cardiac applications, and the understanding of anatomical and physiological properties at molecular and cellular scales. This parallel computational infrastructure can also be used for other complicated systems, providing engineers and scientists with novel technologies to construct accurate computer models. Furthermore, this interdisciplinary project will integrate research and education via novel educational tool and curriculum development as well as outreach activities. Students will interact with collaborative institutions to gain firsthand experience of real issues. Women, minority groups and high school students will be included in the proposed research and education activities through CMU's K-12 Programs. Education activities will be assessed in conjunction with CMU's Eberly Center for Teaching Excellence.