Development of a Miniaturized Wearable Ultrasonic Beam-forming Device for Localized Targeting of Brain Regions in Freely-moving Experimental Subjects

开发微型可穿戴超声波束形成装置，用于对自由移动实验对象的大脑区域进行局部瞄准

• 批准号: 10483847
• 负责人: KEVIN A SNOOK
• 金额: $ 45.03万
• 依托单位: ACTUATED MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10483847
• 关键词: 3-Dimensional; Achievement; Acoustics; Animal Model; Area; Attention; Award; BRAIN initiative; Behavior; Behavioral; Blood specimen; Brain; Brain region; Chemicals; Communities; Control Animal; DYT14 gene; Deep Brain Stimulation; Development; Devices; Dystonia; Electromagnetics; Electronics; Electrophysiology (science); Elements; Enteral Feeding; Epilepsy; FOS gene; Feasibility Studies; Focused Ultrasound; Funding; Goals; Human; Immunohistochemistry; Intervention; Legal patent; Link; Medical; Medical Research; Mental Depression; Mental disorders; Metabolic; Methods; Modality; Motor; Neural Pathways; Neurologic; Neurosciences; Obsessive-Compulsive Disorder; Ohio; Optics; Parkinson Disease; Patient-Focused Outcomes; Performance; Pharmacology; Phase; Physiologic pulse; Public Health; Research; Research Personnel; Research Project Grants; Research Subjects; Resolution; Rodent; Rodent Model; Sales; Small Business Innovation Research Grant; Specificity; Symptoms; System; Technology; Testing; Therapeutic; Transducers; Translations; Ultrasonic Transducer; Ultrasonics; United States National Institutes of Health; Variant; awake; base; behavioral study; commercialization; experimental study; implantation; improved; innovation; instrumentation; interest; light weight; manufacturing scale-up; millimeter; miniaturize; nervous system disorder; neural circuit; neural implant; neuroregulation; next generation; optogenetics; pre-clinical; pre-clinical research; preclinical study; pressure; relating to nervous system; response; sensor; success; tool; ultrasound; user-friendly; verification and validation; vibration; virtual

This Phase I SBIR will further develop, validate, and initiate commercialization of the miniature ultrasound beamforming array (MUBA) system for transcranial focused ultrasound (tFUS). The MUBA system will allow preclinical researchers to reversibly and non-invasively modulate neural activity in intact brain circuits with unparalleled precision. The technology was first developed under a BRAIN initiative-funded exploratory research grant (5R21EY029424; PI: Dr. Kiani). We will ready this system for commercialization for preclinical research applications in response to ‘Translation of BRAIN Initiative Technologies to the Marketplace’ (NOT- MH-21-125) under BRAIN initiative priority area #4: ‘Interventional Tools: link brain activity to behavior with precise interventional tools that change neural circuit dynamics.’ Public Health Problem: The therapeutic utility of brain stimulation, or more generally neuromodulation, in managing numerous neurological and psychiatric diseases is well understood. Deep brain stimulation (DBS) ameliorates Parkinson’s disease symptoms and is being examined for neurological conditions such as dystonia, epilepsy, depression, and obsessive-compulsive disorder. Neuromodulation is also a powerful tool to study brain circuits by being able to selectively activate/inactivate regions (e.g. optogenetics, sonothermogenetics). Currently, neuromodulation can be achieved with different modalities from pharmacological and chemical methods, which lack specificity and have numerous metabolic requirements, to physical methods such as electrical, electromagnetic, optical, and ultrasound. Among noninvasive methods, low-intensity transcranial focused ultrasound (tFUS) stimulation for activation and suppression of neural activity has recently gained more attention due to its improved spatial resolution of millimeter scale relative to its noninvasive counterparts. Conventional tFUS technologies with single-element ultrasound transducers and off-the-shelf driver electronics have limited utility (e.g., fixed/limited brain targeting, bulky) and instrumentation variation limits comparisons that can be made between studies from different labs. The MUBA system will be a lightweight, out-of-the-box solution that researchers can use for dynamic neuromodulation of virtually any region of the brain of awake and behaving research subjects. Aim 1: Optimize, build, and test lightweight MUBA system. Acceptance Criteria. Optimized linear array integrated with beamforming chip, for 2D targeting with millimeter-scale spatial resolution and at least 1 MPa ultrasound pressure at the focal zone. Demonstrate this performance in 10 replicate systems fabricated by AMI team. Aim 2: Validate the MUBA system for precise and effective neuromodulation of brain targets via electrophysiology and immunohistochemistry. Acceptance Criteria: Demonstrate ability to produce millimeter- scale neural activation areas (c-fos immunohistochemistry) at cortical and sub-cortical depths, and steerable excitation (reproducibly and predictably evoked motor response across multiple MUBA systems).

第一阶段 SBIR 将进一步开发、验证微型超声波并启动其商业化 用于经颅聚焦超声（tFUS）的波束形成阵列（MUBA）系统 MUBA 系统将允许。 临床前研究人员可逆地、非侵入性地调节完整大脑回路中的神经活动 该技术最初是在 BRAIN 资助的探索性项目下开发的。 研究补助金（5R21EY029424；PI：Kiani 博士）我们将为该系统的临床前商业化做好准备。 响应“将 BRAIN Initiative 技术转化为市场”的研究应用（非 MH-21-125）在 BRAIN 倡议优先领域#4：“干预工具：将大脑活动与行为联系起来 改变神经回路动态的精确介入工具。” 公共卫生问题：脑刺激或更普遍的神经调节的治疗效用 治疗多种神经和精神疾病已广为人知。 改善帕金森病症状，并正在检查神经系统疾病，例如 神经调节也是治疗肌张力障碍、癫痫、抑郁症和强迫症的有力工具。 通过能够选择性地激活/失活区域来研究大脑回路（例如光遗传学、 目前，神经调节可以通过不同的方式来实现 药理学和化学方法缺乏特异性并且有许多代谢要求， 在非侵入性方法中，例如电、电磁、光学和超声波等物理方法。 低强度经颅聚焦超声 (tFUS) 刺激激活和抑制神经活动 最近由于其相对于其毫米级空间分辨率的提高而受到更多关注 具有单元件超声换能器的传统 tFUS 技术和 现成的驱动电子设备的实用性有限（例如，固定/有限的大脑瞄准、体积庞大）和仪器 变化限制了不同实验室的研究之间的比较。 轻量级、开箱即用的解决方案，研究人员可用于动态神经调节几乎任何 清醒和行为研究对象的大脑区域。 目标 1：优化、构建和测试轻量级 MUBA 系统。 与波束形成芯片集成，用于毫米级空间分辨率和至少 1 MPa 的 2D 瞄准 在 AMI 制造的 10 个复制系统中展示了聚焦区的超声压力。 团队目标 2：通过验证 MUBA 系统对大脑目标进行精确有效的神经调节。 电生理学和免疫组织化学接受标准：展示产生毫米波的能力。 在皮质和皮质下深度缩放神经激活区域（c-fos免疫组织化学），并且可操纵 激发（跨多个 MUBA 系统可重复且可预测地诱发运动反应）。