Ultrasonic Neural Stimulation for Neuromodulation Therapeutics

用于神经调节治疗的超声神经刺激

• 批准号: 9524451
• 负责人: EUN SOK KIM
• 金额: $ 29.66万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9524451
• 关键词: Ablation; Acoustic Stimulation; Acoustics; Action Potentials; Acute; Affect; Area; Brain; Caliber; Cell Death; Cell Membrane Permeability; Characteristics; Chronic; Deep Brain Stimulation; Development; Device Designs; Electric Stimulation; Electrodes; Electrophysiology (science); Epilepsy; Event; Exocytosis; Focused Ultrasound; Foreign Bodies; Frequencies; Goals; Hippocampus (Brain); Histology; In Vitro; Investigation; Ion Channel; Lasers; Length; Lesion; Lighting; Measurement; Measures; Membrane; Membrane Potentials; Methods; Microscope; Monitor; Motor; Neural Inhibition; Neurons; Patch-Clamp Techniques; Pharmacology; Physiologic pulse; Population; Property; Radiation; Rattus; Research; Resistance; Resolution; Rest; Safety; Sensory; Series; Shapes; Signal Transduction; Silicon; Slice; Spottings; Stimulus; Surface; Synaptic Transmission; System; Techniques; Technology; Temperature; Testing; Therapeutic; Time; Tissues; Transducers; Trauma; Ultrasonics; Ultrasonography; Width; base; brain machine interface; brain tissue; design; experimental study; extracellular; insight; minimally invasive; nervous system disorder; neural prosthesis; neural stimulation; neuroregulation; novel; patch clamp; pressure; relating to nervous system; response; sound

Summary/Abstract Electrical stimulation of neural tissue, such as deep brain stimulation (DBS) and cortical stimulation, is widely applied therapeutic neuromodulation techniques for neurologic disorders. Penetrating electrodes (e.g., microwires and silicon probes) for DBS provide high spatial resolution, but are invasive, displacing neural tissue, producing acute insertion trauma, and potentially eliciting a foreign-body response. Surface electrodes, while less invasive, cannot generate a highly-localized electrical field. Motivated by these limitations, the goal of this proposal is to develop minimally-invasive and yet highly-localized neuronal stimulation using ultrasound. Focused acoustic beams with high energy are traditionally used for cellular ablation. Here, we propose to use low acoustic energy to avoid any ablation or lesion, exploiting the unprecedented features of Self-Focusing Acoustic Transducers (SFATs) that can focus 2 - 20 MHz sound waves at a sub-mm-sized area with electrically tunable focal length and force direction. We will conduct intracellular and extracellular experiments to determine the value and underlying mechanisms of neuromodulation effects induced by SFAT-based ultrasonic stimulation. The aims of this project are (1) to determine the optimal SFAT designs and fabricate SFATs with novel properties for the proposed intracellular and extracellular experiments and (2) to characterize the neuromodulatory function evoked by SFAT-based ultrasound stimulation in normal brain slices and test its neuromodulatory effect in epileptic brain slices. Using patch clamp and extracellular recording methods, we will monitor ionic flux and local field potentials, respectively, while varying the acoustic stimulation frequency, intensity, pulse width, pulse shape and pulse repetition frequency as well as the focal spot(s), focal size and force direction. The safety of acoustic stimulation will be assessed by histology. This project will provide insights into biologic mechanisms of ultrasonic neural stimulation, and if successful, could be a critical step toward the development of a minimally invasive alternative to neuromodulation by electrical stimulation in the treatment of neurologic disorders such as epilepsy.

摘要/摘要 神经组织的电刺激（例如深脑刺激（DB）和皮质刺激）广泛 用于神经系统疾病的应用治疗性神经调节技术。穿透电极（例如， DBS的微管和硅探针）可提供高空间分辨率，但具有侵入性，可取代神经 组织，产生急性插入创伤，并可能引起外国体现反应。表面电极， 虽然侵入性较小，但不能产生高度定位的电场。受这些限制的动机，目标 该建议的是使用超声开发最低侵入性但高度定位的神经元刺激。 传统上，具有高能量的聚焦声束用于细胞消融。在这里，我们建议使用 低声能量以避免任何消融或病变，利用自我焦点的前所未有的特征 声音传感器（SFAT），可以将2-20 MHz的声波聚焦在一个亚MM大小的区域， 电气可调的焦距和力方向。我们将进行细胞内和细胞外实验 确定基于SFAT引起的神经调节作用的值和潜在机制 超声刺激。该项目的目的是（1）确定最佳SFAT设计并制造 SFAT具有新的特性，用于提议的细胞内和细胞外实验，（2）表征 基于SFAT的超声刺激在正常脑切片中引起的神经调节功能并测试其 癫痫脑切片中的神经调节作用。使用斑块夹和细胞外记录方法，我们将 分别监测离子通量和局部场电位，同时改变声刺激频率， 强度，脉搏宽度，脉搏形状和脉搏重复频率以及焦点，焦点尺寸和 力方向。声学刺激的安全将通过组织学评估。这个项目将提供 洞悉超声神经刺激的生物学机制，如果成功，可能是关键的步骤 通过在刺激中开发微创替代神经调节的替代品 治疗神经系统疾病，例如癫痫。