Diversity Supplement for 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的多样性补充，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: 10786355
• 负责人: KEVIN A SNOOK
• 金额: $ 2.41万
• 依托单位: ACTUATED MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10786355
• 关键词: 3-Dimensional; Acceleration; Achievement; Acoustics; Animal Model; Area; Attention; Award; BRAIN initiative; Behavior; Behavioral; Blood specimen; Brain; Brain region; Cephalic; Certification; Chemicals; Communities; Control Animal; 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; Marketing; Medical; Medical Research; Mental Depression; Mental disorders; Metabolic; Methods; Modality; Motor; Movement; Neural Pathways; Neurologic Examination; Neurosciences; Obsessive-Compulsive Disorder; Ohio; Optics; Parkinson Disease; Patient-Focused Outcomes; Penetration; Performance; Phase; Physiologic pulse; Public Health; Reproducibility; 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; behavioral study; commercialization; experimental study; implantation; improved; innovation; instrumentation; interest; light weight; manufacturing scale-up; millimeter; miniaturize; nervous system disorder; neural; neural circuit; neural implant; neuroregulation; next generation; optogenetics; pharmacologic; pre-clinical; pre-clinical research; preclinical study; pressure; 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 at cortical and sub-cortical depths (c-fos immunohistochemistry), and steerable excitation (reproducibly and predictably evoked motor response across multiple MUBA systems).

I阶段I SBIR将进一步发展，验证和启动微型超声的商业化 用于经颅聚焦超声（TFU）的波束形成阵列（MUBA）系统。 Muba系统将允许 临床前研究人员可在完整的脑电路中可逆和非侵入性调节神经活动 无与伦比的精度。该技术最初是根据大脑倡议资助的探索性开发的 研究补助金（5R21EY029424; PI：Kiani博士）。我们将为临床前的商业化准备该系统 研究应用程序响应“大脑启动技术向市场的翻译”（不是 MH-21-125）在大脑倡议优先区域下 改变神经电路动态的精确介入工具。’ 公共卫生问题：大脑刺激的治疗效用，或更普遍的神经调节 众所周知，管理许多神经系统和精神病。深脑刺激（DBS） 缓解帕金森氏病症状，并正在检查神经系统疾病，例如 肌张力障碍，癫痫，抑郁和强迫症。神经调节也是一个强大的工具 通过能够选择性激活/灭活区域来研究脑电路（例如，光遗传学， Sonothermogenetics）。目前，可以通过不同的方式来实现神经调节 药理学和化学方法缺乏特异性并且有许多代谢要求，以 物理方法，例如电磁，光学和超声。在无创方法中， 低强度thrancranial聚焦超声（TFU）模拟，以激活和抑制神经活动 最近由于其相对于毫米的空间分辨率改善了相对于其毫米的空间分辨率，最近引起了人们的关注 无创的对应物。带有单元素超声传感器的常规TFU技术和 现成的驱动器电子设备的实用性有限（例如，固定/有限的大脑靶向，笨重）和仪器 不同实验室研究之间可以进行的变异限制比较。 Muba系统将是 研究人员可以将其用于动态神经调节的轻巧，开箱即用的解决方案。 清醒和行为研究主题的大脑区域。 AIM 1：优化，构建和测试轻型MUBA系统。接受标准。优化的线性阵列， 与波束形成芯片集成，以毫米尺度的空间分辨率和至少1 MPa进行2D靶向 焦距的超声压力。在AMI制造的10个重复系统中演示这种性能 团队。 AIM 2：验证MUBA系统通过 电生理学和免疫组织化学。接受标准：证明产生毫米的能力 皮质和亚皮质深度（C-FOS免疫组织化学）的缩放神经激活区域，并进行可辨 令人兴奋的（可重复且可预测地诱发了多个MUBA系统的运动响应）。