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

传统的心脏消融术是一种使用热能破坏小面积心脏组织的医疗手术，该心脏组织导致房颤（AF）患者的心跳快速且不规则。非热不可逆电穿孔（IRE）消融器械使用短但强的电场在心脏细胞中产生永久性孔，目前正在接受美国食品药品监督管理局（FDA）器械和放射卫生中心（CDRH）的安全性和有效性审查。在该项目中，将使用细胞死亡和心脏组织电特性的可量化测量来开发首个此类数值IRE消融心脏模型，以预测特定消融脉冲参数集的消融区大小。该模型有可能减少IRE器械开发中的临床和动物试验，为FDA监管审查过程提供信息，并最终加速AF患者获得创新、安全和有效的器械。这项工作将与弗吉尼亚理工大学（VT）的教师和学生以及CDRH/FDA的监管科学家合作。该项目的目标是在COMSOL Multiphysics上开发一个数字三维心脏模型，该模型具有心脏组织的代表性几何形状，适用于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衍生的心肌细胞（hiPSC-CM）获得的电穿孔的电场阈值和在离体猪心中测量的心脏组织的动态电导率来告知修改的拉普拉斯方程以确定双针电极设置的电势分布。该模型将通过有限的离体研究进行验证，以确认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，使用新的硅体外方法，弗吉尼亚理工大学和FDA将开发一种用于不可逆电穿孔消融的数字心脏模型，产生一种可扩展的工具，可以扩展到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填补目前基础知识和监管知识的空白，为优化心脏消融器械开发的IRE脉冲参数提供强大的工具，促进对用于AF治疗的IRE技术的理解，并帮助解决2.7- 610万美国人受到这种常见的心律失常的影响，可导致心力衰竭和中风。该奖项反映了NSF的法定使命，并被认为值得支持通过使用基金会的知识价值和更广泛的影响审查标准进行评估。

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.