Mechanistic Monitoring of Ultrasound Neuromodulation

中枢神经系统疾病影响美国数百万患者目前的药物 治疗往往伴随着副作用，如运动障碍、神志不清、头晕、 失眠、抑郁、病态赌博等。神经调节可以是 通过深度受限的非侵入性技术或具有侵入性的手术 可以深入到很深的地方。在过去的几年里，经颅聚焦超声(FUS)已经被 被证明在体内既能刺激又能抑制大脑活动。超声波有几种 与上述脑深部刺激技术相比具有优势，因为它可以穿透 大脑穿过完整的头皮和头骨超过几厘米。考虑到它的完全非侵入性 这项技术具有非电离性质，已被证明可用于人脑研究 具有深度穿透(几厘米)，不需要引入电极或光学 大脑中的纤维。在拟议的研究中，我们将致力于利用技术专长 由调查组提供，以便制定对潜在的物理和 体内和实时的生理机制同步技术将 允许翻译成人类。要研究的三种物理机制是辐射。 力、空化和灌流，所有这些都可以结合FUS调制进行监控 被私家侦探的小组。因此，拟议研究的基本假设是，如果这些 底层机制或其组合可以在应用期间被监控，FUS 可以更有针对性和更好地监测，以改善其重复性和最优化。至 为此，我们从超声波组建了一支互补性很强的多学科团队 工程学、解剖学和功能成像、神经科学、神经学、神经工程学和 神经外科。建议的方法学需要突破现有的FUS方法学。 用来有选择地聚焦(几毫米量级)并驾驭两个浅层 和深层区域(大约几厘米深)，以及关于 超声波产生的物理效应(即辐射力或空化-机械组织效应) 在大脑上)和生理(即，由于上述机械的结果的神经元效应 组织效应)的实时机制。因此，这项研究旨在优化靶向性和有效性 通过映射FUS神经调节的物理机制，从而更好地探索非侵入性 首次在人类中调节运动和动机反应以达到终极目的 治疗从运动到精神障碍的各种情况。

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.