ASCENT (Automated Simulations to Characterize Electrical Nerve Thresholds): A pipeline for sample-specific computational modeling of electrical stimulation of peripheral nerves.
ASCENT (Automated Simulations to Characterize Electrical Nerve Thresholds): A pipeline for sample-specific computational modeling of electrical stimulation of peripheral nerves.
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DOI：
10.1371/journal.pcbi.1009285
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发表时间：
2021-09
影响因子：
4.3
通讯作者：
Pelot NA
中科院分区：
文献类型：
--
作者：
Musselman ED;Cariello JE;Grill WM;Pelot NA
电刺激和周围神经阻滞对于治疗一系列疾病和病症有着巨大的希望，但临床前研究的有希望的结果往往无法转化为成功的临床治疗。不同物种的神经解剖结构存在差异，需要不同的电极和刺激参数才能实现等效的神经反应，并且很难解释这些因素的后果。我们描述了标准化、模块化和可扩展的计算建模管道的实现、验证和应用，用于周围神经内神经纤维的电激活和阻滞的生物物理模拟。 ASCENT（表征电神经阈值的自动模拟）管道提供了一套内置功能，供用户控制整个工作流程，包括用于组装电极的零件库、生物材料的电特性、先前发布的纤维模型和常见刺激波形。我们验证了 ASCENT 计算的准确性，验证了测试版的可用性，并提供了几个令人信服的 ASCENT 实施模型示例。 ASCENT 将实现模拟数据的可重复性，并将用作与其他模型（例如器官系统模型）集成模拟的组成部分，以解释实验结果，并设计实验和临床干预措施，以促进周围神经刺激疗法的发展。尽管临床前研究取得了有希望的结果，但由于物种间神经解剖结构的差异，使用周围神经电刺激的新疗法往往无法产生成功的临床结果。这些差异通常需要不同的电极与神经连接和/或不同的刺激参数以实现等效的神经反应。此外，不同人群神经解剖结构的差异导致神经对刺激的反应存在差异。这些物种间和个体间的差异可以使用个体特异性周围神经形态和生物物理特性的计算模型来研究。为了加速个体神经解剖学的计算建模过程，我们开发了 ASCENT，这是一个软件平台，用于通过定制电极和刺激参数模拟样本特定神经对电刺激的反应。 ASCENT 可自动执行构建临床前和临床研究计算模型所需的复杂、多步骤过程，并使用生物物理真实模拟设计新颖的刺激方案。 ASCENT 管道将用于开发提高刺激选择性和效率的技术，并加速新型周围神经刺激疗法向临床的转化。
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. Despite promising results from preclinical studies, novel therapies using electrical stimulation of peripheral nerves often fail to produce successful clinical outcomes due to differences in neural anatomy across species. These differences often require different electrodes to interface with the nerves and/or different stimulation parameters to achieve equivalent nerve responses. Further, differences in nerve anatomy across a population contribute to differences in nerve responses to stimulation. These inter-species and inter-individual differences can be studied using computational modeling of individual-specific peripheral nerve morphology and biophysical properties. To accelerate the process of computational modeling of individual nerve anatomy, we developed ASCENT, a software platform for simulating the responses of sample-specific nerves to electrical stimulation with custom electrodes and stimulation parameters. ASCENT automates the complex, multi-step process required to build computational models of preclinical and clinical studies and to design novel stimulation protocols using biophysically realistic simulations. The ASCENT pipeline will be used to develop technologies that increase the selectivity and efficiency of stimulation and to accelerate the translation of novel peripheral nerve stimulation therapies to the clinic.
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