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.

说明.提出了一种高密度Stim-Grid MAP脊髓刺激电极导线技术， 建立预测地图，详细说明下尿路神经通路如何通过高- 密度刺激骶髓和神经根。这些地图将使有原则的发展， 神经调节疗法，其使用脊髓刺激来减轻膀胱过度活动症的负担， 失禁下尿路（LUT），包括膀胱、尿道和相关的肌肉和神经， 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被 在超过200，000人中植入，与器械相关的不良事件仍然很常见， 尽管有了很大的改善，许多人仍然需要处理膀胱过度活动症和尿失禁的不必要的症状。使用 电场建模，我们的多学科团队已经证明，电极的两倍增加， 柱和密度可以将刺激传递到横向定位的脊髓目标， 临床电极此外，我们已经证明了制造超柔性电极的可行性， 可以符合骶骨脊髓的神经丛几何形状。这项技术开发工作的目标是 是开发和商业化包含8列和8行的64通道有源引线， 通过脊髓刺激的LUT周围神经的可达性的地图。我们力求做到三个 开发任务：（目标1）开发一种轮廓和被动高密度硬膜外脊髓桨阵列， (AIM 2）：开发带有开关矩阵电子组件的STIM-GRID MAP脊髓桨（AIM 3） 通过骶髓高分辨率刺激绘制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1年，我们将创建并演示48通道灵活的高密度无源电极导线，并创建 描述盆腔神经、阴部神经和阴部神经分支的选择性通路。在第二年，我们将 演示仅使用16根导线的8列8行（64通道分辨率）刺激网格MAP阵列。 高分辨率的阵列将使我们能够生成LUT周围神经进入脊髓的地图， 重要的是，它可以立即扩展到映射其他器官模型，而只需很少的额外开发工作和时间。 由于刺激网格MAP技术基于众所周知的植入式脊髓电极导线植入 技术，这项技术可以迅速转化为高分辨率的脊髓映射实验， 在OT 3阶段的术中设置期间的人。