Multiscale cardiac fluid-structure-growth model

针对患者的计算模型在彻底改变疾病管理和推进心力衰竭治疗方面具有巨大潜力。过去二十年来，心脏计算模型的理论和计算发展取得了重大进展。然而，目前缺乏一个完整的计算模型，能够考虑跳动心脏中发生的所有主要物理现象，特别是心脏的电传导、血流动力学、心壁运动力学以及心脏功能和几何形状的长期变化。缺乏这样的建模框架是发展有关心脏功能和疾病的深入知识的关键障碍。尤其如此，因为这些物理相互作用是设计心脏病治疗和了解心脏功能时需要考虑的重要方面。该项目旨在开发一个强耦合的心脏机电-液体生长计算模型框架，该框架考虑了跳动心脏中发生的关键物理原理。 研究生和本科生都将参与该研究项目。所提出的自下而上的多尺度模型将是通用的，允许任意3D心脏几何形状以及多尺度物理，包括：（i）细胞兴奋-收缩耦合过程，（ii）心脏组织中发现的成分对其各向异性机械行为的贡献，（iii）心壁和血液之间的宏观流体结构相互作用，以及（iv）长期生长和重塑过程。本项目将实现的具体目标如下。首先，将基于混合虚拟域任意拉格朗日欧拉公式开发强耦合心脏机电流体建模框架，以描述由细胞兴奋收缩耦合过程驱动的血流和心室壁变形之间的短期双向流体弹性结构相互作用。其次，基于时间尺度分离原理，将心脏生长模型集成到建模框架中，以描述由病理生理损伤驱动的心脏几何形状和功能的长期变化。最后，通过从合作者获得的临床数据，PI 将应用建模框架来发展对正常和异常心脏功能的新认识，例如肥厚型心肌病中心室壁几何形状异常和变形导致血流阻塞所产生的短期和长期影响。

Patient-specific computational models have tremendous potential in revolutionizing disease management and advancing heart failure treatments. Significant advances have been made in the last twenty years on the theoretical and computational developments of cardiac computational models. However, there is currently a lack of a complete computational model that is capable of taking into account all the principal physics occurring in a beating heart, specifically, electrical conduction in the heart, dynamics of blood flow, mechanics of the cardiac wall motion, and the long-term changes in heart function and geometry. The lack of such a modeling framework is a critical barrier to the development of in-depth knowledge about the heart function and diseases. This is especially so as the interactions of these physics are important aspects that need to be taken into account when designing heart disease treatments and understanding heart function. The proposed project aims to develop a strongly-coupled cardiac electromechanics-fluid-growth computational modeling framework that takes into account the key principal physics occurring in the beating heart. Both graduate and undergraduate students will be involved with the research project.The proposed bottom-up multiscale model will be versatile to allow for arbitrary 3D heart geometries as well as multiscale physics, including: (i) cellular excitation-contraction coupling processes, (ii) contribution of constituents found in the cardiac tissue to its anisotropic mechanical behavior, (iii) macroscale fluid-structure interactions between the heart wall and blood, and (iv) long term growth and remodeling processes. Specific goals that will be accomplished in this project are as follows. First, a strongly coupled cardiac electromechanics-fluid modeling framework will be developed based on a hybrid Fictitious-Domain Arbitrary-Lagrange-Eulerian formulation to describe the short-term bidirectional fluid-elastic-structure interactions between blood flow and ventricular wall deformation driven by the cellular excitation-contraction coupling processes. Second, a cardiac growth model will be integrated into the modeling framework based on the principle of timescale separation to describe long-term changes in the heart geometry and function driven by pathophysiological insults. Last, with clinical data obtained from collaborators, the PIs will apply the modeling framework to develop new understanding concerning normal and abnormal heart functions, such as the short- and long-term effects arising from flow obstruction due to abnormalities in the geometry and deformation of the ventricular wall in hypertrophic cardiomyopathy.