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

心脏颤动计算机模型的开发、验证和验证

• 批准号: 1347015
• 负责人: Flavio Fenton
• 金额: $ 9.06万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-10-01 至 2015-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1347015&HistoricalAwards=false
• 关键词: Development; verification; validation; computer; models

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.

该 NSF-FDA 驻场学者奖支持建模领域的转化研究，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理事会计算机和网络系统部的 NSF 网络物理系统计划的支持。心源性猝死是工业化世界中死亡的主要原因。美国有五分之一的人患有某种心脏病，三分之一的死亡是由心脏病造成的，每年造成的经济影响约为 2000 亿美元。大多数死亡是由心律失常引起的，特别是心颤，这是一种快速、无序的电活动。将心律失常分类为折返性或局灶性心律失常具有临床意义，但难以评估。 FDA 负责监管旨在实现这一重要差异化的系统和算法。这种区分是一项复杂的任务，涉及对电活动的复杂时空模式的分析。该项目的目标是确定模型应代表的颤动的关键特征，比较现有模型与这些特征的测量值的对应程度，并开发更好地代表颤动的模型。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)。该项目旨在 1) 验证和创建新模型，不仅可以重现单细胞动力学，还可以重现组织中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 不仅可以使用该框架来测试心脏电生理设备还可以表征和验证通过计算机辅助药物设计方法获得的大量提交的治疗化合物。该研究是与 FDA 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 更好地监管和验证用于治疗和终止心律失常的设备的安全性和有效性。该项目的所有结果将免费提供给研究界和公众。