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: 10579309
• 负责人: LEE E FISHER
• 金额: $ 59.72万
• 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/10579309
• 关键词: Action Potentials; Amputees; Anatomy; Animal Experiments; Animals; Ankle; Area; Back; Chronic; Complex; Computer Models; Computer Simulation; Custom; Data; Development; Devices; Diameter; Distal; Dorsal; Dura Mater; Electric Stimulation; Electrodes; Elements; Equilibrium; Esthesia; Experimental Animal Model; 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; Microsurgery; Modeling; Nerve; Neurostimulation procedures of spinal cord tissue; Operative Surgical Procedures; Pattern; Peripheral Nerve Stimulation; Peripheral Nerves; Persons; Resected; Safety; Sensory; Silicones; Spinal Cord; Structure; Study models; Surface; System; Techniques; Thick; Thinness; Time; Tissues; Travel; Width; design; epidural space; experimental study; fall risk; flexibility; foot; high resolution imaging; implantable device; implantation; improved; limb amputation; mechanical properties; meter; nerve supply; neural; neurophysiology; novel; pressure; prosthesis control; 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.

项目概要/摘要 设计和驱动方面的进步使假肢取得了巨大的进步。然而，这些设备不能 提供感觉反馈，导致步态缓慢并增加跌倒的风险。我们实验室的最新证据表明 刺激脊髓和背根的横向结构可以有效地在远端四肢产生感觉。 在这些研究中，横向 SCS (LSCS) 会引起截肢手或脚区域的感觉，尽管其中许多 感觉还覆盖了残肢的更近端区域。为了在缺失的肢体上获得更多的焦点感觉 将需要开发具有更小触点、更紧密的触点间间距以及更好的排列的电极 目前存在 SCS 电极。此外，由于外侧硬膜外间隙比硬膜外间隙更窄且更弯曲。 与传统的 SCS 中线目标相比，这些新型 SCS 电极必须比现有的 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，通过选择性刺激外侧神经来恢复感觉 脊髓中的结构。在这个项目中，我们将描述 DR 如何响应 LSCS 并优化 用于刺激这些结构的电极设计。通过结合大型动物神经生理学实验， 通过组织学分析和计算建模研究，我们将表征 LSCS 的选择性和设计 电极可最大限度地提高选择性并实现足部和踝部的局灶性感觉异常覆盖，同时避免损伤 底层神经组织。为了实现这些目标，我们将完成以下目标： 目标 1：量化腰椎 DR 的功能组织和 LSCS 的选择性。 我们将通过记录诱发动作电位的逆向传播来测量猫 LSCS 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，同时 选择性刺激个体 DR 来表征其神经支配模式和体位排列。 目标 2：开发解剖学上精确的脊髓计算模型（包括 DR）并使用该模型 模型作为设计 LSCS 电极的平台。 利用人类脊髓的高分辨率成像数据和显微外科测量，我们将建立一个 结合有限元和等效电路模型来模拟横向结构的解剖学和神经生理学 人类脊髓及其对 LSCS 的反应。我们将使用这个平台来设计电极触点的布局 LSCS 设备以及刺激配置和波形，以最大限度地提高个体 DR 刺激的选择性。 目标 3：进行大型动物手术以优化 LSCS 电极基板的机械性能 避免神经损伤并保持电极放置的长期稳定性。 在猪身上，我们将长期植入具有多种不同机械基底设计的 LSCS 电极，包括 改变设备的横截面和任何可能有助于设备插入和稳定的工具。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。