Delivery of Precision Acoustic Fields to Penetrating Neural Implants to Improve Longevity and Performance of the Neural Interface

向穿透性神经植入物提供精密声场，以提高神经接口的寿命和性能

• 批准号: 9973249
• 负责人: Natasha Noel Tirko
• 金额: $ 34.09万
• 依托单位: ACTUATED MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-05 至 2021-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9973249
• 关键词: Acoustic Stimulation; Acoustics; Acute; Address; Affect; Amputees; Anti-Inflammatory Agents; Astrocytes; Blood - brain barrier anatomy; Brain; Brain-Derived Neurotrophic Factor; Cerebrum; Chemicals; Chondroitin ABC Lyase; Chronic; Cicatrix; Clinical; Collection; Control Animal; Coupled; Development; Devices; Dexamethasone; Disease; Effectiveness; Electrodes; Enzymes; Equipment Malfunction; Failure; Foreign Bodies; Frequencies; Geometry; Goals; Head; Health; Histology; Immune response; Immunity; Impairment; Implant; Implanted Electrodes; Injury; Intervention; Knowledge; Life; Liquid substance; Longevity; Measures; Mechanics; Medical; Meninges; Microdialysis; Microelectrodes; Microglia; Modeling; Nervous system structure; Neuroglia; Neurons; Neurophysiology - biologic function; Noise; Paraplegia; Performance; Periodicity; Peripheral; Peripheral Nervous System; Pharmacological Treatment; Physiologic pulse; Process; Prosthesis; Rattus; Research; Resolution; Rodent; Sampling; Scheme; Shunt Device; Signal Transduction; Site; Technology; Temperature; Therapeutic; Thinness; Time; Tissue Model; Tissues; Transducers; Ultrasonic Transducer; Ultrasonics; Ultrasonography; Ventricular; Work; brain machine interface; clinical translation; cost; design; electric impedance; healing; implantable device; implantation; improved; in vivo; in vivo Model; innovation; insight; method development; migration; motor control; mouse model; nervous system disorder; neural implant; neuroprosthesis; neurotransmission; neurotrophic factor; next generation; operation; pre-clinical; prevent; programs; relating to nervous system; response; side effect; vibration

This program evaluates the application of precision acoustic fields to penetrating neural implants to prevent electrode impedance rise and improve implant longevity. Problem to be solved: Chronic neural implants hold great potential for illuminating features of neural function and treating neurological disorders. Penetrating electrode arrays provide direct access to neural signals across the central and peripheral nervous system with high spatial resolution. A consistent point of failure for chronically implanted microelectrode arrays is the poor longevity and functionality of these devices, an issue that must be addressed to facilitate clinical translation of neural implant technology. One major failure mode of electrode arrays is the host tissue’s immune response (i.e., foreign body response or FBR), which causes glial scarring and neural cell loss near electrode sites, impairing recording quality. Efforts have been made to minimize the brain FBR through electrode design and pharmacological treatment, but there is no optimal solution; performance variability persists for all array types. We propose an innovative means of reducing the FBR by using low-intensity pulsed ultrasound to acoustically promote localized neurotrophic release in cortical tissue surrounding a neural implant. Studies will also focus on implanted transducers and provide new insights into the possible neuroprotective effects of frequencies above conventional transcranial ultrasound studies. Hypothesis. Application of localized ultrasonic fields of different acoustic parameters and treatment intervals can affect release of neurotrophic factors, and can be used to mitigate glial scarring, promote neural implant longevity, and neuron health. Aim 1 – Design and characterize head-mounted ultrasound transducer for chronic in vivo studies. Acceptance Criteria: Acoustic stimulation is well-coupled and is thermally safe (<1°C temperature increase in tissue model). Aim 2 – Identify ultrasonic parameters that safely stimulate acute neurotrophin release in cortical tissue below neural activation thresholds, in an in vivo model. Acceptance Criteria: Significantly increase neurotrophin release (e.g., BDNF) with low-intensity ultrasound stimulation, as measured through cerebral fluid sampling via an implanted microdialysis probe and tissue histology, without damaging neural tissue. Aim 3 – Evaluate effects of low-intensity ultrasound stimulation on long-term neural electrode performance and glial scarring in cortical tissue in an in vivo model. Acceptance Criteria: Significantly (α=0.05) reduce the change in electrode impedance as compared to experimental control (no acoustic stimulation); significantly (α=0.05) improve neural recording quality (number of neural units, signal-to- noise ratios), over a 4-week period. Aim 4 – Evaluate the effects of low-intensity ultrasound stimulation on the microglia response to a neural implant in an in vivo model. Acceptance Criteria: Significant reduction in microglia activation and migration within 200 µm of the electrode-tissue interface with periodic low-intensity ultrasound stimulation over a 4-week period.

该计划评估精密声场在穿透神经植入物中的应用，以防止 电极阻抗上升并提高植入物的寿命。 待解决的问题：慢性神经植入物在阐明神经功能特征方面具有巨大潜力 穿透电极阵列可以直接获取神经信号。 具有高空间分辨率的中枢和周围神经系统的一致故障点。 长期植入的微电极阵列是这些设备的寿命和功能较差的一个问题 必须解决这一问题，以促进神经植入技术的临床转化。 电极阵列是宿主组织的免疫反应（即异物反应或FBR），这会导致神经胶质细胞 电极部位附近的疤痕和神经细胞损失，损害了记录质量。 通过电极设计和药物治疗最小化大脑FBR，但没有最佳方案 解决方案；我们提出了一种减少阵列类型的创新方法。 FBR 通过使用低强度脉冲超声波以声学方式促进皮质中的局部神经营养物质释放 研究还将关注植入的传感器并提供新的见解。 研究频率高于传统经颅超声研究的可能的神经保护作用。 假设。不同声学参数和治疗间隔的局部超声场的应用 可影响神经营养因子的释放，可用于减轻神经胶质疤痕、促进神经植入 目标 1 – 设计和表征头戴式超声换能器。 慢性体内研究接受标准：声刺激耦合良好且热安全（<1°C）。 目标 2 – 确定可安全刺激急性炎症的超声参数 在体内模型中，皮质组织中神经营养蛋白的释放低于神经激活阈值。 标准：通过低强度超声刺激显着增加神经营养素释放（例如 BDNF），如 通过植入的微透析探针和组织组织学的脑液取样进行测量，无需 目标 3 – 评估低强度超声刺激对长期神经组织的影响。 体内模型中的电极性能和皮质组织中的神经胶质疤痕。 与实验对照（无 声刺激）；显着（α=0.05）提高神经记录质量（神经单元数量、信号到- 目标 4 – 评估低强度超声刺激对 体内模型中小胶质细胞对神经植入物的反应接受标准：显着减少。 电极-组织界面 200 µm 范围内的小胶质细胞活化和迁移，具有周期性低强度 为期 4 周的超声刺激。