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的商业化 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， 无与伦比的精确度这项技术最初是在一项由BRAIN计划资助的探索性研究中开发的。 研究资助（5 R21 EY 029424; PI：Kiani博士）。我们将为临床前商业化做好准备 研究应用，以响应“翻译大脑倡议技术的市场”（不是- MH-21-125）根据BRAIN倡议优先领域#4：“干预工具：将大脑活动与行为联系起来， 精确的介入工具来改变神经回路的动力学 公共卫生问题：脑刺激的治疗效用，或更普遍的神经调节， 管理许多神经和精神疾病是众所周知的。脑深部电刺激（DBS） 改善帕金森病症状，并正在检查神经系统疾病， 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/激活区域来研究脑回路（例如光遗传学， sonothermogenetics）。目前，神经调节可以用不同的模态来实现， 药理学和化学方法，缺乏特异性，并有许多代谢要求， 物理方法，例如电学、电磁学、光学和超声。在非侵入性方法中， 用于激活和抑制神经活动的低强度经颅聚焦超声（tFUS）刺激 最近由于其相对于其改进的毫米尺度的空间分辨率而获得了更多的关注。 非侵入性对应物。采用单元件超声换能器的传统tFUS技术， 现成的驱动器电子设备具有有限的实用性（例如，固定/有限脑靶向，体积大）和仪器 差异限制了不同实验室研究之间的比较。MUBA系统将是一个 研究人员可以使用的轻量级，开箱即用的解决方案，用于动态神经调制的几乎任何 清醒和有行为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。优化线阵 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目标定位 聚焦区的超声压力。在AMI制造的10个重复系统中证明此性能 团队目的2：通过以下方式验证MUBA系统对脑靶点的精确有效的神经调节 电生理学和免疫组织化学。验收标准：证明有能力生产毫米- 皮层和皮层下深度的神经激活区（c-fos免疫组织化学）， 兴奋（在多个MUBA系统中可重复和可预测地诱发运动反应）。

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).