Mechanistic Monitoring of Ultrasound Neuromodulation

超声神经调节的机械监测

• 批准号: 9765827
• 负责人: Elisa E. Konofagou
• 金额: $ 66.37万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-04 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765827
• 关键词: Acoustics; Affect; Animals; Brain; Brain region; Central Nervous System Diseases; Confusion; Deep Brain Stimulation; Dizziness; Dyskinetic syndrome; Electrodes; Electroencephalography; Electrophysiology (science); Engineering; Feedback; Fiber Optics; Focused Ultrasound; Functional Imaging; Functional Magnetic Resonance Imaging; Human; Image; Immunohistochemistry; Link; Mechanics; Membrane; Mental Depression; Mental disorders; Methodology; Methods; Midbrain structure; Monitor; Motivation; Motor; Movement; Mus; Mydriasis; Nature; Neurology; Neurons; Neurosciences; Pathological Gambling; Patients; Penetration; Perfusion; Pharmacotherapy; Physiological; Procedures; Radiation; Reporting; Reproducibility; Research Personnel; Risk; Rodent; Saccades; Scalp structure; Sleeplessness; Structure; System; Technical Expertise; Techniques; Technology; Testing; Time; Tissues; Ultrasonography; anatomic imaging; behavioral outcome; brain tissue; cranium; design; healthy volunteer; hemodynamics; human subject; improved; in vivo; limb movement; millimeter; multidisciplinary; neuroregulation; neurosurgery; non-drug; nonhuman primate; novel; response; side effect; simulation; tool; translation to humans

Central Nervous System diseases affect several millions of patients in the U.S. Current drug treatments are often associated with side-effects such as dyskinesia, confusion, dizziness, insomnia, depression, and pathological gambling among others. Neuromodulation can be achieved either with noninvasive techniques that are depth limited or invasive procedures that can go to large depths. Over the past few years, transcranial focused ultrasound (FUS) has been shown capable of both stimulating and suppressing brain activity in vivo. Ultrasound has several advantages over the aforementioned technologies for deep brain stimulation as it can penetrate the brain over several centimeters through the intact scalp and skull. Given its entirely noninvasive and nonionizing nature, the technique has been shown to be translatable to human brain studies with deep penetration (of several centimeters) without requiring introduction of electrodes or optic fibers inside the brain. In the proposed study, we will aim to harness from the technical expertise available by the group of investigators so as to develop monitoring of the underlying physical and physiological mechanisms in vivo and in real time and simultaneously sync technologies that will allow translation to humans. The three physical mechanisms to be investigated are radiation force, cavitation and perfusion, all of which can be monitored in conjunction with FUS modulation by the PI’s group. Therefore, the underlying hypothesis of the proposed studies is that if these underlying mechanisms, or the combination thereof, can be monitored during application, FUS can be more targeted and better monitored to improve on its reproducibility and optimization. To this end, we have assembled a highly complementary, multi-disciplinary team from ultrasound engineering, anatomical and functional imaging, neuroscience, neurology, neuroengineering and neurosurgery. The methodologies proposed require breakthroughs in current FUS methodologies used in order to selectively focus (on the order of a few millimeters) and steer across both shallow and deep-seated regions (on the order of several centimeters in depth) as well as informing on the physical (i.e., radiation force or cavitation - mechanical tissue effects exerted by ultrasound on the brain) and physiological (i.e., neuronal effects as a result of the aforementioned mechanical tissue effects) mechanism in real time. This study is thus aimed to optimize targeting and efficacy of FUS neuromodulation by mapping the physical mechanism so as to better explore noninvasive modulation of motor and motivation responses in humans for the first time for the ultimate treatment of conditions ranging from movement to psychiatric disorders.

中枢神经系统疾病影响美国目前的数百万患者 治疗通常与副作用有关，例如运动障碍，混乱，头晕， 失眠，抑郁和病理赌博等。神经调节可以 通过无创的技术来实现，该技术是深度有限的或侵入性的程序 可以进入大深度。在过去的几年中，thrancranial专注的超声波（FUS）一直是 显示能够在体内刺激和抑制大脑活性。超声有几个 比优先技术的优势技术可以穿透，因为它可以穿透 通过完整的头皮和头骨，大脑在几厘米上。鉴于其完全无创的 和非电离性质，该技术已被证明可以翻译成人脑研究 具有深度渗透（数厘米），而无需引入电极或光学元件 大脑内部的纤维。在拟议的研究中，我们将旨在利用技术专长 由调查人员小组获得，以开发对基础物理和 生理机制在体内和实时以及同时同步技术 允许翻译为人类。要研究的三种物理机制是辐射 力，气腔和灌注，所有这些都可以与FUS调制一起监测 由PI小组。因此，拟议的研究的基本假设是，如果这些假设 可以在应用过程中监视基本机制或其组合 可以更具针对性和更好的监控，以改善其可重复性和优化。到 这最后，我们组装了一支从超声波 工程，解剖和功能成像，神经科学，神经学，神经工程和 神经外科。提出的方法需要在当前的FUS方法中进行突破 用于选择性地集中精力（几毫米的顺序），并跨过两个浅 和深处的区域（以深度为几厘米的顺序），并通知 物理（即辐射力或空化 - 超声施加的机械组织效应 在大脑上）和生理学（即，由于预先提前的机械作用而导致神经元作用 组织效应）实时机制。因此，这项研究的目的是优化目标和有效性 通过映射物理机制来更好地探索非侵入性，通过映射FUS神经调节 首次对人类的运动和动机反应调节最终 治疗从运动到精神疾病的疾病。