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).
Public Health Relevance Statement: Project narrative: This project will commercialize an innovative ultrasound beamforming technology, developed in an academic research lab, to facilitate dissemination to the neuroscience community. The system will be the first commercially-available transcranial focused ultrasound system for small-subject preclinical studies. Long term project goals include feasibility studies for human stimulation for therapeutic treatment of conditions like Parkinson's.
Project Terms: Achievement; Achievement Attainment; Acoustics; Acoustic; Attention; Award; Behavior; Mental disorders; Mental health disorders; Psychiatric Disease; Psychiatric Disorder; mental illness; psychiatric illness; psychological disorder; Brain; Brain Nervous System; Encephalon; Communities; Mental Depression; depression; Dystonia; Muscle Dystonia; Electromagnetics; Electronics; electronic device; Electrophysiology (science); Electrophysiology; Neurophysiology / Electrophysiology; electrophysiological; Elements; Epilepsy; Epileptic Seizures; Epileptics; Seizure Disorder; epilepsia; epileptiform; epileptogenic; Feasibility Studies; Goals; Human; Modern Man; Immunohistochemistry; Immunohistochemistry Cell/Tissue; Immunohistochemistry Staining Method; instrumentation; Methods; NIH; National Institutes of Health; United States National Institutes of Health; Nervous System Diseases; Neurologic Disorders; Neurological Disorders; neurological disease; nervous system disorder; Neural Pathways; Neurosciences; Obsessive-Compulsive Neurosis; Obsessive-Compulsive Disorder; Ohio; optical; Optics; Paralysis Agitans; Parkinson; Parkinson's disease; Parkinsons disease; Primary Parkinsonism; Parkinson Disease; Patents; Legal patent; Pharmacology; pressure; Public Health; Research; Investigators; Researchers; Research Personnel; Rodentia; Rodents Mammals; Rodent; Sales; Specificity; Technology; Testing; Transducers; Translations; Medical Research; Research Subjects; FOS gene; G0S7; Protooncogene FOS; c fos; c-fos Gene; c-fos Proto-Oncogenes; v-FOS FBJ Murine Osteosarcoma Viral Oncogene Homolog; Enteral Feeding; enteric feeding; feeding tube; gastric feeding; tube feeding; base; Blood specimen; Blood Sample; sensor; Ultrasonic Transducer; Ultrasound transducer; improved; Area; Phase; Variant; Variation; Medical; Neurologic; Neurological; Link; Chemicals; awake; Funding; R-Series Research Projects; R01 Mechanism; R01 Program; Research Grants; Research Projects; Research Project Grants; Therapeutic; Metabolic; lightweight; light weight; tool; Pulse; Physiologic pulse; Deep Brain Stimulation; millimeter; System; 3-D; 3D; three dimensional; 3-Dimensional; vibration; interest; Performance; success; neural control; neural regulation; neuromodulation; neuromodulatory; neuroregulation; Animal Models and Related Studies; model of animal; model organism; Animal Model; neural; relating to nervous system; Modality; Devices; neural circuitry; neurocircuitry; synaptic circuit; synaptic circuitry; neural circuit; response; miniaturize; Intervention Strategies; interventional strategy; Intervention; Brain region; dystonia 14; DYT14 gene; Ultrasonic; Ultrasonics; Symptoms; Control Animal; Motor; Resolution; Patient-Focused Outcomes; Patient outcome; Patient-Centered Outcomes; Rodent Model; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Development; developmental; Behavioral; pre-clinical; preclinical; preclinical study; pre-clinical study; virtual; next generation; innovation; innovate; innovative; pre-clinical research; preclinical research; user-friendly; implantation; commercialization; manufacturing scale-up; verification and validation; optogenetics; behavioral study; behavior study; Focused Ultrasound; BRAIN initiative; Brain Research through Advancing Innovative Neurotechnologies initiative; experimental study; experiment; experimental research; neural implant; brain implant; ultrasound
