Epidural Current-Steering for Selective Modulation of Lower Urinary Tract Function

硬膜外电流引导选择性调节下尿路功能

• 批准号: 10008078
• 负责人: Bryan L McLaughlin
• 金额: $ 74.15万
• 依托单位: MICRO-LEADS, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10008078
• 关键词: Action Potentials; Adverse event; Afferent Pathways; Aging; Anatomy; Axon; Biological Assay; Biological Models; Bladder; Bladder Control; Chronic; Clinical; Communication; Critical Pathways; Data; Data Coordinating Center; Development; Device or Instrument Development; Devices; Disease; Dura Mater; Electrodes; Electromyography; Electronics; Electrophysiology (science); Encapsulated; Functional disorder; Future; Geometry; Human; Impairment; Implant; Implanted Electrodes; Incontinence; Injury; Lasers; Lead; Lower urinary tract; Maps; Measures; Methods; Modeling; Molds; Monitor; Motor; Muscle; Nerve; Neurostimulation procedures of spinal cord tissue; Organ; Organ Model; Output; Overactive Bladder; Parasympathetic Nervous System; Pathway interactions; Pelvis; Performance; Peripheral Nerves; Phase; Physiologic pulse; Physiological; Physiology; Positioning Attribute; Process; Quality of life; Research; Resolution; Sacral spinal cord structure; Silicon; Silicones; Sphincter; Spinal Cord; Spinal nerve root structure; Stretching; Structure; Surface; Symptoms; System; Techniques; Technology; Thick; Thinness; Time; Translating; Universities; Urethra; Water; afferent nerve; base; body system; clinically relevant; cost; density; electric field; experience; experimental study; flexibility; functional improvement; implantation; improved; in vivo; intravesical; multidisciplinary; nanofiber; neural circuit; neuroregulation; novel; pressure; prevent; recruit; relating to nervous system; response; spinal cord mapping; technology development; tool

DESCRIPTION. A high-density Stim-Grid MAP spinal cord stimulation lead technology is proposed to enable the creation of predictive maps that detail how lower urinary tract nerve pathways can be activated through high- density stimulation of the sacral spinal cord and roots. These maps will enable principled development of neuromodulation therapies that use spinal cord stimulation to alleviate the burden of overactive bladder and incontinence. The lower urinary tract (LUT), consisting of the bladder, urethra and associated muscles and nerves, is an important target organ system for neuromodulation therapies as injury, disease and aging can lead to impairment and subsequent reductions in the quality of life. While existing neuromodulation devices have been implanted in over 200,000 people, device related adverse events remain common, and despite functional improvements, many people still deal with unwanted symptoms of overactive bladder and incontinence. Using electric field modelling, our multidisciplinary team has demonstrated that a two-fold increase in electrode columns and density can deliver stimulation to laterally-positioned spinal cord targets not possible with existing clinical electrodes. Furthermore, we have demonstrated feasibility of manufacturing ultra-flexible electrodes that can conform to the plexus geometry of the sacral spinal cord. The objective of this technology development effort is to develop and commercialize a 64-channel active-lead which contains 8-columns and 8 rows, and to develop maps of the accessibility of LUT peripheral nerves through spinal cord stimulation. We seek to perform three development tasks: (AIM 1) Develop a contoured and passive high-density epidural spinal-cord paddle array, (AIM 2): Develop a STIM-GRID MAP spinal cord paddle with a switch-matrix electronics package, (AIM 3) Develop maps of LUT recruitment by high-resolution stimulation of the sacral spinal cord. Our multi-disciplinary team includes device development (Micro-Leads) and bladder electrophysiology (University of Pittsburgh). In Year 1 we will create and demonstrate a 48-channel flexible and high-density passive lead and create maps that describe the selective access to the pelvic nerve, pudendal nerve and pudendal nerve branches. In Year 2 we will demonstrate a Stim-Grid MAP array with 8 columns and 8-rows (64-channels of resolution) using only 16 wires. The high-resolution array will enable us to generate maps of LUT peripheral nerve access at the spinal cord, but importantly, is immediately scalable to map other organ models with little additional development effort and time. Because the Stim-Grid MAP technology is based on well-understood implantable spinal cord lead implantation techniques, this technology could be rapidly translated to high-resolution spinal cord mapping experiments in people during an intraoperative settings in an OT3 phase.

描述。提出了一种高密度 Stim-Grid MAP 脊髓刺激导线技术，以实现 创建预测图，详细说明如何通过高强度激活下尿路神经通路 骶脊髓和神经根的密度刺激。这些地图将有助于原则性的发展 使用脊髓刺激来减轻膀胱过度活动症负担的神经调节疗法 失禁。下尿路 (LUT)，由膀胱、尿道以及相关的肌肉和神经组成， 是神经调节治疗的重要靶器官系统，因为损伤、疾病和衰老可能导致 损害和随后的生活质量下降。虽然现有的神经调节装置已经 植入超过 200,000 人的设备中，与设备相关的不良事件仍然很常见，尽管功能正常 尽管有所改善，但许多人仍然面临膀胱过度活动症和尿失禁的不良症状。使用 电场建模，我们的多学科团队已经证明，电极增加了两倍 柱和密度可以向横向定位的脊髓目标提供刺激，这是现有技术不可能实现的 临床电极。此外，我们还证明了制造超柔性电极的可行性 可以符合骶脊髓的神经丛几何形状。这项技术开发工作的目标 是开发和商业化包含8列和8行的64通道有源引线，并开发 通过脊髓刺激 LUT 周围神经的可及性图。我们力求实现三 开发任务：（目标 1）开发轮廓和被动高密度硬膜外脊髓桨阵列， (目标 2)：开发带有开关矩阵电子封装的 STIM-GRID MAP 脊髓板，(目标 3) 通过对骶脊髓进行高分辨率刺激来绘制 LUT 募集图。我们的多学科 团队包括设备开发（Micro-Leads）和膀胱电生理学（匹兹堡大学）。在 第一年，我们将创建并演示 48 通道灵活且高密度的无源引线，并创建地图 描述选择性进入盆腔神经、阴部神经和阴部神经分支。在第二年，我们将 演示了仅使用 16 根电线的 8 列和 8 行（64 通道分辨率）的 Stim-Grid MAP 阵列。 高分辨率阵列将使我们能够生成脊髓周围神经通路的 LUT 地图，但是 重要的是，它可以立即扩展以绘制其他器官模型，而无需额外的开发工作和时间。 因为 Stim-Grid MAP 技术基于众所周知的可植入脊髓导线植入 技术，该技术可以快速转化为高分辨率脊髓绘图实验 OT3 阶段术中环境中的人员。