NSF/FDA SIR: Numerical heart model for irreversible electroporation ablation

传统的心脏消融是一种使用热能破坏一小块心脏组织的医疗程序，这种组织会导致心房颤动(AF)患者出现快速而不规则的心跳。非热不可逆电穿孔(IRE)消融设备使用短但强的电场在心脏细胞中形成永久性毛孔，目前正在接受食品和药物管理局(FDA)设备和放射健康中心(CDRH)的安全性和有效性审查。在这个项目中，我们将利用细胞死亡和心脏组织电特性的可量化测量来建立首个此类数值消融心脏模型，以预测一组特定消融脉冲参数的消融区域的大小。这种模式有可能减少IRE设备开发中的临床和动物试验，为FDA的监管审查过程提供信息，并最终加速房颤患者获得创新、安全和有效的设备。这项工作将与弗吉尼亚理工大学(VT)的教职员工和学生以及CDRH/FDA的监管科学家合作。该项目的目标是开发一个基于COMSOL多物理的三维心脏数值模型，该模型具有心脏组织的典型几何形状，适合模拟脉冲电场心脏消融中的可逆、不可逆电穿孔和热损伤效应。该模型将使用从人诱导多能干细胞来源的心肌细胞(hiPSC-CM)获得的电穿孔的电场阈值和在体外猪心脏中测量的心脏组织的动态电导率来提供修正的拉普拉斯方程，以确定两针电极装置的电位分布。该模型将通过有限的体外研究进行验证，以证实该数值模型使用大型动物组织模型预测组织中病变体积的能力。因此，弗吉尼亚理工大学和FDA将利用这一新的体外硅方法，开发一个用于不可逆电穿孔消融的心脏数值模型，产生一个可扩展的可扩展工具，用于预测具有不同电极阵列的其他器官的IRE消融治疗。该项目的成功完成将解决目前基础和监管知识方面的空白，为心脏消融设备开发的IRE脉冲参数优化提供强大的工具，增进对用于房颤治疗的IRE技术的了解，并帮助解决270万至610万受这种可能导致心力衰竭和中风的常见心律失常影响的美国人的迫切公共卫生需求。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。

Traditional cardiac ablation is a medical procedure that uses thermal energy to destroy a small area of heart tissue that is causing rapid and irregular heartbeats in atrial fibrillation (AF) patients. Non-thermal irreversible electroporation (IRE) ablation devices use short but strong electrical fields to create permanent pores in heart cells and are currently under safety and effectiveness review by the Center for Devices and Radiological Health (CDRH) at the Food and Drug Administration (FDA). In this project, a first-of-its-kind numerical IRE ablation heart model will be developed using quantifiable measurements of cell death and electrical properties of heart tissue to predict the size of ablation zone for a particular set of ablation pulse parameters. This model has the potential to decrease clinical and animal testing in the IRE device development, inform the FDA regulatory review process and ultimately accelerate AF patients access to innovative, safe and effective devices. The work will partner faculty and students at Virginia Tech (VT) and regulatory scientists at the CDRH/FDA.The goal of this project is to develop a numerical three-dimensional heart model on COMSOL Multiphysics with a representative geometry of heart tissue suitable for simulation of reversible, irreversible electroporation and thermal damage effects in pulsed electric field cardiac ablation. The model will use electric field thresholds of electroporation obtained from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and dynamic conductivity of cardiac tissues measured in ex vivo porcine heart to inform a modified Laplace equation to determine electric potential distribution of a two-needle electrode setup. The model will be validated with limited ex vivo studies to confirm the capability of the numerical model to predict lesion volume in tissues using a large animal tissue model. Therefore, using the novel in silico-in vitro approach, Virginia Tech and the FDA will develop a numerical heart model for irreversible electroporation ablation, producing a scalable tool that can be extended to predicting IRE ablation treatments of other organs with varied electrode arrays. Successful accomplishment of this project will address current gaps in fundamental and regulatory knowledge, provide robust tool for optimization of IRE pulse parameters for cardiac ablation device development, advance understanding of IRE technology for AF treatment, and help address an urgent public health need for 2.7-6.1 million Americans affected by this common cardiac arrhythmia that can lead to heart failure and stroke.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.