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、验证和启动微型超声波的商业化