Development, verification, and validation of computer models of cardiac fibrillation

这一NSF-FDA常驻学者奖支持建模方面的转化性研究，为未来的医疗器械设计和审批流程提供信息。它得到了计算机和信息科学与工程局计算机和网络系统部门的NSF网络物理系统计划的支持。突发性心脏病死亡是工业化世界中死亡的主要原因。在美国，五分之一的人受到某种心脏病的影响，三分之一的死亡是由于心脏病，每年造成的经济影响约为2000亿美元。这些死亡中的大多数是由于心律失常，特别是纤颤，这是一种快速、无组织的电活动。将心律失常分为折返性心律失常或局灶性心律失常具有临床意义，但难以评估。FDA负责监管旨在做出这一重要区分的系统和算法。这种区分是一项复杂的任务，需要分析复杂的电活动时空模式。该项目的目标是确定模型应该表示的纤颤的关键特征，比较现有模型与这些特征的测量值的对应程度，并开发更好地表示纤颤的模型。该项目开发和扩展细胞和组织模型，并从FDA监管科学的角度探索临床、实验和模拟数据的分析，包括验证、确认和不确定性量化(VVUQ)。该项目寻求1)验证和创建新的模型，不仅再现单细胞动力学，而且再现组织中的实验和临床相关的生理动力学；2)启动一个新的开发框架，FDA不仅可以用来测试心脏电生理设备，还可以用来表征和验证通过计算机辅助药物设计方法获得的大量治疗化合物的提交。这项研究是与FDA的设备和放射健康中心合作进行的，旨在开发能够表征和评估设备实际性能的工具。这将有助于FDA更好地监管和验证为治疗和终止心律失常而开发的设备的安全性和有效性。该项目的所有成果将免费提供给研究界和公众。

This NSF-FDA Scholar-In-Residence award supports translational research in modeling to inform future medical device design and approval processes. It is supported by the NSF Cyber-Physical Systems program in the Division of Computer and Network Systems in the Directorate for Computer and Information Science and Engineering.Sudden cardiac death is the leading cause of fatalities in the industrialized world. One in five people in the United States is affected by some sort of heart disease and one third of all deaths are due to cardiac diseases with an economic impact of about $200 billion a year. Most of these deaths result from arrhythmias, particularly fibrillation, which is rapid, disorganized electrical activity. The classification of arrhythmias as either reentrant or focal is of clinical significance, yet is difficult to assess. The FDA is responsible for regulating the systems and algorithms that aim to make this important differentiation. Such differentiation is a complex task involving the analysis of complex spatio-temporal patterns of electrical activity. The objectives of this project are to identify the key features of fibrillation that models should represent, to compare how well (or poorly) existing models correspond to measured values of these features, and to develop models that better represent fibrillation. The project develops and extends cell and tissue models and explores the analysis of clinical, experimental and simulation data from the perspective of regulatory science at the FDA, including verification, validation, and uncertainty quantification (VVUQ). The project seeks to 1) validate and create new models that reproduce not only single-cell dynamics, but also experimental and clinically relevant physiological dynamics in tissue and 2) initiate a new developmental framework that the FDA can use not only to test cardiac electrophysiology devices but also to characterize and verify massive submissions of therapeutic compounds obtained by computer-aided drug design methods. The research is conducted in collaboration with the Center for Devices and Radiological Health at FDA, and is aimed at developing tools that can characterize and evaluate real-world performance of devices. This will help the FDA to better regulate and verify the safety and effectiveness of devices that are developed to treat and terminate cardiac arrhythmias. All results from this project will be made freely available to the research community and to the general public.