Modeling Activation and Block of Autonomic Nerves for Analysis and Design

自主神经激活和阻滞建模用于分析和设计

• 批准号: 10003460
• 负责人: Warren M. Grill
• 金额: $ 85.79万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-02 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10003460
• 关键词: Abdomen; Address; Algorithms; Animal Model; Animals; Autonomic Nerve Block; Beds; Benchmarking; Biological Models; Cervical; Characteristics; Complement; Computer Simulation; Computers; Data; Development; Devices; Diabetes Mellitus; Dimensions; Electrodes; Elements; Engineering; Experimental Designs; Female; Fiber; Frequencies; Ganglia; Geometry; Goals; Heart Diseases; Heart failure; Human; Implant; Individual; Individual Differences; Location; Maps; Medicine; Methods; Microanatomy; Modeling; Morphology; Nerve; Nerve Fibers; Outcome; Output; Pacemakers; Performance; Phase; Physiological; Population; Positioning Attribute; Property; Rattus; Research Personnel; Sampling; Series; Shapes; Specific qualifier value; Stimulus; System; Testing; Therapeutic; Therapeutic Intervention; Vagus nerve structure; Validation; autonomic nerve; base; body system; design; experimental study; histological specimens; male; novel; programs; response; side effect; simulation; species difference; tool; vagus nerve stimulation

Experiments to map physiological functions of autonomic nerves and the continued advance of bioelectronic therapies are limited by inadequate activation or block of targeted nerve fibers and unwanted co-activation or block of non-targeted nerve fibers. More fundamentally, the relationship between applied stimuli and the nerve fibers that are activated or blocked, how this relationship varies across individuals and species, and how these relationships can be controlled remain largely unknown. We will develop, implement and validate an efficient computational pipeline for simulation of electrical activation and block of different nerve fiber types within autonomic nerves. The pipeline will include segmentation of microanatomy from fixed nerve samples, three- dimensional finite-element models of electrodes positioned on nerves, and non-linear cable models of different nerve fiber types, enabling calculation of quantitative input-output maps of activation and block of specific nerve fibers. As key benchmarks of pipeline development and for the proposed analysis and design efforts, we will implement models of the cervical (VNc) and abdominal (VNa) vagus nerves in rat, in a SPARC-identified animal model, and in human. The VNc is an excellent test bed as it contains a broad spectrum of nerve fiber types, there are experimental data to facilitate model validation, and there are multiple applications of VNc stimulation where a lack of fiber selectivity limits the therapeutic window. The VNa is an excellent complement to the cervical VNc, as a prototypical autonomic nerve of a size comparable to many of the small autonomic nerves targeted by SPARC projects. We will use the models that emerge from the pipeline to achieve analysis and design goals to address critical gaps identified as SPARC priorities. Specifically, we will quantify of the effects of intra-species differences in nerve morphology on activation and block by building individual sample-specific models for each nerve and specie. These models will also be used to quantify inter-species differences in nerve fiber activation and block and to identify electrode designs and stimulation parameters that produce equivalent degrees of activation and block across species. We will combine the resulting models with engineering optimization to design approaches to increase the selectivity and efficiency of activation and block of different nerve fiber types. The outcomes will be a pipeline for modeling autonomic nerves, electrode geometries, and stimulation parameters, as well as tools that address the limitations of nerve stimulation selectivity and efficiency that hinder the continued advance of physiological mapping studies and the development of bioelectronic therapies.

绘制自主神经生理功能的实验和生物电子学的持续发展 治疗受到靶向神经纤维的不充分激活或阻断以及不需要的共激活或阻断的限制 非靶向神经纤维阻滞。更根本的是，施加的刺激和神经之间的关系 激活或阻断的纤维，这种关系如何在个体和物种之间变化，以及这些 关系可以被控制仍然在很大程度上未知。我们将开发、实施和验证一个有效的 用于模拟内部不同神经纤维类型的电激活和阻断的计算流水线 自主神经管道将包括从固定神经样本中分割显微解剖结构，三个- 定位在神经上的电极的三维有限元模型，以及不同电极的非线性电缆模型。 神经纤维类型，能够计算特定神经的激活和阻滞的定量输入-输出图 纤维作为管道开发的关键基准，以及拟议的分析和设计工作，我们将 在经SPARC鉴定的动物中，在大鼠中实施颈部（VNc）和腹部（VNa）迷走神经模型 模型，在人类。VNc是一个很好的测试平台，因为它包含广泛的神经纤维类型， 有实验数据来促进模型验证，并且有VNc刺激的多种应用 其中缺乏纤维选择性限制了治疗窗口。该VNa是一个很好的补充颈椎 VNc是一种典型的自主神经，其大小与许多靶向的小自主神经相当 的项目。我们将使用管道中出现的模型来实现分析和设计目标 解决被确定为可持续发展优先事项的关键差距。具体来说，我们将量化物种内的影响， 通过为每个神经元构建个体样本特异性模型， 神经和物种。这些模型也将用于量化神经纤维激活的物种间差异 并且识别产生等效程度的刺激的电极设计和刺激参数 激活和阻断跨物种。我们将联合收割机与工程优化相结合， 设计方法以增加不同神经纤维类型的激活和阻断的选择性和效率。 这些成果将成为自主神经、电极几何形状和刺激建模的管道 参数，以及解决阻碍神经刺激的神经刺激选择性和效率的限制的工具。 生理绘图研究的持续进展和生物电子疗法的发展。