Electrodes for selective stimulation of the lateral spinal cord to restore sensation after lower-limb amputation

用于选择性刺激外侧脊髓以恢复下肢截肢后感觉的电极

• 批准号: 10365095
• 负责人: LEE E FISHER
• 金额: $ 63.43万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10365095
• 关键词: Action Potentials; Amputation; Amputees; Anatomy; Animal Experiments; Animals; Ankle; Area; Back; Caliber; Chronic; Complex; Computer Models; Computer Simulation; Custom; Data; Development; Devices; Distal; Dorsal; Dura Mater; Electric Stimulation; Electrodes; Elements; Equilibrium; Esthesia; Family suidae; Felis catus; Gait; Geometry; Goals; Hand; Hindlimb; Histologic; Hour; Human; Image; Impairment; Implant; Individual; Injury; Intractable Pain; Lateral; Limb Prosthesis; Limb structure; Lower Extremity; Measurement; Measures; Mechanics; Modeling; Nerve; Neurostimulation procedures of spinal cord tissue; Operative Surgical Procedures; Pattern; Peripheral Nerves; Persons; Residual state; Safety; Sensory; Silicones; Spinal; Spinal Cord; Structure; Study models; Surface; System; Techniques; Thick; Time; Tissues; Travel; Width; design; epidural space; experimental study; fall risk; flexibility; foot; high resolution imaging; implantable device; implantation; limb amputation; mechanical properties; nerve supply; neurophysiology; novel; pressure; prosthesis control; relating to nervous system; residual limb; response; sensory feedback; somatosensory; spinal nerve posterior root; tissue injury; tool

PROJECT SUMMARY/ABSTRACT Advances in design and actuation have led to dramatic improvements in prosthetic limbs. However, these devices cannot provide sensory feedback, which leads to slow gait and increased risk of falling. Recent evidence from our lab has shown that stimulation of lateral structures in the spinal cord and dorsal roots can effectively generate sensations in the distal limbs. In these studies, lateral SCS (LSCS) evoked sensations in regions of the amputated hands or feet, though many of these sensations also covered more proximal regions of the residual limb. To achieve more focal sensations in the missing limb will require development of electrodes with smaller contacts, tighter inter-contact spacing, and better arrangements than currently exist for SCS electrodes. Further, because the lateral epidural space is narrower and more curved than the traditional midline target of SCS, these novel SCS electrodes must be thinner and more flexible than existing SCS devices. Our long-term goal is to create a neurostimulation system to restore sensation by selectively stimulating lateral structures in the spinal cord. In this project, we will characterize how the DR respond to LSCS and optimize electrode design for stimulating these structures. Through a combination of large animal neurophysiology experiments, histological analyses, and computational modeling studies, we will characterize the selectivity of LSCS and design electrodes to maximize selectivity and achieve focal paresthetic coverage of the foot and ankle while avoiding injury to the underlying neural tissue. To achieve these goals, we will complete the following aims: Aim 1: Quantify functional organization of the lumbar DR and selectivity of LSCS. We will measure the selectivity of LSCS in cats by recording antidromic propagation of evoked action potentials in nerves throughout the hindlimb. We will also resect the dura and use hook electrodes to repeat these experiments while selectively stimulating individual DR to characterize their innervation patterns and somatotopic arrangement. Aim 2: Develop an anatomically-accurate computational model of the spinal cord, including the DR, and use that model as a platform to design LSCS electrodes. Utilizing high-resolution imaging data and microsurgical measurements of the human spinal cord, we will build a combined finite element and equivalent circuit model to simulate the anatomy and neurophysiology of lateral structures in the human spinal cord and their response to LSCS. We will use this platform to design the layout of electrode contacts on the LSCS device and stimulation configurations and waveforms to maximize selectivity of stimulation of individual DR. Aim 3: Perform large animal surgeries to optimize the mechanical properties of the LSCS electrode substrate to avoid neural damage and maintain chronic stability of electrode placement. In pigs, we will chronically implant LSCS electrodes with multiple different mechanical substrate designs, including varying the cross-section of the device and any tooling that may aide in insertion and stabilization of the device. We will perform histological analysis to characterize tissue damage and the relationship between mechanical properties and tissue injury.

项目摘要/摘要 设计和驱动的进步导致了假肢的显着改善。但是，这些设备不能 提供感官反馈，从而导致步态缓慢并增加跌落的风险。我们实验室的最新证据已显示 刺激脊髓和背部根部的横向结构可以有效地在远端的肢体中产生感觉。 在这些研究中，横向SC（LSC）唤起了截肢或脚区域的感觉，尽管其中许多 感觉还涵盖了残留肢体的近端区域。在缺失的肢体中获得更多的焦点感觉 将需要开发具有较小触点的电极，更紧密的互接触间距和更好的布置 目前存在于SCS电极。此外，由于外侧硬膜外空间比 SCS的传统中线目标，这些新颖的SCS电极必须比现有SCS设备更薄，更灵活。 我们的长期目标是创建一个神经刺激系统，通过选择性刺激横向来恢复感觉 脊髓中的结构。在这个项目中，我们将表征博士对LSC的反应并优化 用于刺激这些结构的电极设计。通过大型动物神经生理学实验的组合， 组织学分析和计算建模研究，我们将表征LSC和设计的选择性 电极以最大化选择性并实现脚和脚踝的焦距覆盖范围，同时避免受伤 基础神经组织。为了实现这些目标，我们将完成以下目标： AIM 1：量化LBAR DR的功能组织和LSC的选择性。 我们将通过记录诱发动作电位的抗肿瘤传播来衡量猫中LSC的选择性 整个后肢的神经。我们还将切除硬脑膜，并使用钩电极重复这些实验 有选择地刺激个人DR来表征其神经支配模式和体体布置。 目标2：开发脊髓的解剖精确计算模型，包括DR，并使用该模型 模型作为设计LSC电极的平台。 利用人脊髓的高分辨率成像数据和显微外科测量值，我们将建立一个 合并有限元和等效电路模型，以模拟横向结构的解剖学和神经生理学 人脊髓及其对LSC的反应。我们将使用此平台设计电极触点的布局 LSCS设备和刺激配置和波形，以最大程度地提高单个DR刺激的选择性。 目标3：进行大型动物手术，以优化LSC电极底物的机械性能 避免神经损伤并保持电极位置的慢性稳定性。 在猪中，我们将长期使用具有多种不同机械底物设计的长期植入LSC电极，包括 改变设备的横截面以及任何可能在设备插入和稳定方面的工具。我们将 进行组织学分析以表征组织损伤以及机械性能与组织之间的关系 受伤。