Mechanistic Monitoring of Ultrasound Neuromodulation

中枢神经系统疾病影响着美国数百万患者。 治疗通常伴随有副作用，例如运动障碍，意识模糊，头晕， 失眠、抑郁、病态赌博等等。神经调节可以是 通过深度有限的非侵入性技术或侵入性手术实现， 可以到达很深的地方。在过去的几年里，经颅聚焦超声（FUS）已被 显示能够刺激和抑制体内大脑活动。超声波有几个 与上述脑深部电刺激技术相比， 穿过完整的头皮和头骨几厘米鉴于其完全非侵入性 和非电离性质，该技术已被证明可用于人类大脑研究 具有深穿透（几厘米）而不需要引入电极或光学器件 大脑内部的纤维在拟议的研究中，我们的目标是利用 调查人员小组可以提供，以便监测基本的物理和 生理机制在体内和在真实的时间，同时同步技术， 翻译成人类。要研究的三种物理机制是辐射 力、空化和灌注，所有这些都可以与FUS调制一起监测 被私家侦探的小组因此，拟议研究的基本假设是，如果这些 潜在的机制，或其组合，可以在应用过程中监测，FUS 可以更有针对性和更好地监测，以提高其重现性和优化。到 为此，我们组建了一支高度互补的多学科团队， 神经科学、神经病学、神经工程学和 神经外科所提出的方法需要在现有的FUS方法上有所突破 用于选择性地聚焦（在几毫米的量级上）并在两个浅的 和深层次的地区（在几厘米深的数量级），以及提供信息， 物理的（即，辐射力或空化-超声施加的机械组织效应 在大脑上）和生理上（即，神经元效应作为上述机械 组织效应）机制。因此，本研究旨在优化靶向和疗效 FUS神经调节的物理机制，以便更好地探索非侵入性 人类运动和动机反应的调制首次为最终的 治疗从运动到精神障碍的各种疾病。

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.