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

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).