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

第一阶段SBIR将进一步开发、验证和启动微型超声波的商业化 用于经颅聚焦超声的波束形成阵列(MUBA)系统。MUBA系统将允许 临床前研究人员可逆地和非侵入性地调节完整脑回路中的神经活动 无与伦比的精确性。这项技术最初是在一项由大脑倡议资助的探索项目下开发的 研究资助(5R21EY029424；PI：Kiani博士)。我们将为该系统的临床前商业化做好准备 研究应用应对“脑创新技术向市场的转化”(非- MH-21-125)在大脑倡议优先领域#4：‘干预工具：将大脑活动与行为联系起来 精确的介入工具可以改变神经回路的动态。 公共卫生问题：脑刺激的治疗效用，或更广泛地说，神经调节，在 许多神经和精神疾病的管理是众所周知的。脑深部刺激(DBS) 改善帕金森氏症的症状，并正在接受神经系统疾病的检查，如 肌张力障碍、癫痫、抑郁症和强迫症。神经调节也是一种强大的工具 通过能够选择性地激活/停用区域(例如光遗传学， 声热遗传学)。目前，神经调节可以通过不同的方式实现 药理和化学方法缺乏特异性，需要大量的代谢，以 物理方法，如电、电磁、光学和超声波。在非侵入性方法中， 低强度经颅聚焦超声刺激对神经活动的激活和抑制 最近获得了更多的关注，因为它相对于它的 非侵入性对应物。具有单元件超声换能器的传统tFUS技术和 现成的驱动器电子设备的实用性有限(例如，固定/有限的大脑定位、笨重)和仪器 差异限制了来自不同实验室的研究之间的比较。MUBA系统将是一个 轻量级、开箱即用的解决方案，研究人员可以使用该解决方案来动态调整几乎任何 清醒的和行为正常的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。验收标准。优化的线阵 与波束形成芯片集成，可实现毫米级空间分辨率和至少1兆帕的2D目标 焦点区域的超声压力。在由AMI制造的10个复制系统中演示这一性能 一队。目的2：验证MUBA系统对大脑靶点的精确和有效的神经调节 电生理学和免疫组织化学。验收标准：证明有能力生产毫米级- 皮质和皮质下深度的鳞状神经激活区(c-fos免疫组织化学)，可操纵 激励(可重复和可预测地在多个MUBA系统中诱发运动响应)。

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).