Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America.
Department of Computer Science, Duke University, Durham, North Carolina, United States of America.
PLoS Comput Biol. 2021 Sep 7;17(9):e1009285. doi: 10.1371/journal.pcbi.1009285. eCollection 2021 Sep.
Electrical stimulation and block of peripheral nerves hold great promise for treatment of a range of disease and disorders, but promising results from preclinical studies often fail to translate to successful clinical therapies. Differences in neural anatomy across species require different electrodes and stimulation parameters to achieve equivalent nerve responses, and accounting for the consequences of these factors is difficult. We describe the implementation, validation, and application of a standardized, modular, and scalable computational modeling pipeline for biophysical simulations of electrical activation and block of nerve fibers within peripheral nerves. The ASCENT (Automated Simulations to Characterize Electrical Nerve Thresholds) pipeline provides a suite of built-in capabilities for user control over the entire workflow, including libraries for parts to assemble electrodes, electrical properties of biological materials, previously published fiber models, and common stimulation waveforms. We validated the accuracy of ASCENT calculations, verified usability in beta release, and provide several compelling examples of ASCENT-implemented models. ASCENT will enable the reproducibility of simulation data, and it will be used as a component of integrated simulations with other models (e.g., organ system models), to interpret experimental results, and to design experimental and clinical interventions for the advancement of peripheral nerve stimulation therapies.
电刺激和外周神经阻断在治疗一系列疾病和障碍方面具有巨大的潜力,但临床前研究中的有希望的结果往往未能转化为成功的临床治疗。不同物种的神经解剖结构需要不同的电极和刺激参数来实现等效的神经反应,并且很难考虑到这些因素的后果。我们描述了一种标准化、模块化和可扩展的计算建模管道的实现、验证和应用,用于在周围神经内对电激活和纤维阻断进行生物物理模拟。ASCENT(自动模拟以确定神经阈值)管道提供了一套内置功能,供用户完全控制整个工作流程,包括用于组装电极的部件库、生物材料的电气特性、已发表的纤维模型以及常见的刺激波形。我们验证了 ASCENT 计算的准确性,在测试版中验证了其可用性,并提供了几个引人注目的 ASCENT 实施模型的示例。ASCENT 将使模拟数据的可重复性,并将其用作与其他模型(例如器官系统模型)的集成模拟的一部分,以解释实验结果,并设计用于推进周围神经刺激治疗的实验和临床干预措施。