High resolution electrical brain mapping by real-time and portable 4D Acoustoelectric Imaging

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 DESCRIPTION (provided by applicant): Our vision is to develop the first noninvasive, real-time and portable electrical brain mapping system based on disruptive acoustoelectric (AE) technology. Our goal is to overcome limitations with functional brain imaging and electroencephalography (EEG), which suffers from poor resolution and inaccuracies due to the blurring of electrical signals as they pass through the brain and skull. Acoustoelectric Brain Imaging (ABI) implements pulsed ultrasound (US) to transiently modulate local tissue resistivity. As the US interacts with neural currents, a voltage modulation ("AE signal") is generated at the US frequency and detected by a distant electrode. This AE signal is proportional to the local current density and spatially confined to the US focus. By rapidly scanning a focused US beam in the brain and detecting the modulation signals, 4D ABI could achieve accurate, real-time, volumetric images of current densities through the adult human skull with a resolution near 1 mm3. Before transcranial ABI can be safely and effectively employed as a tool for functional human brain imaging, several major obstacles must be overcome. The greatest challenge is detecting the weak AE interaction signal through the skull, while maintaining safe US exposure to the head and brain. We, therefore, propose several strategies to dramatically enhance detection of the AE signal by a factor of 10 or more without compromising patient safety. Through a careful team-oriented planning process, we will design and develop the first ABI platform for evaluation and optimization in a realistic head phantom and, later, performance testing in living rat and pig brains. To address these and other challenges, we propose to 1) Develop the first-of-its-kind US delivery system capable of transcranial ABI; 2) Devise methods to dramatically improve detection of the AE signal through bone and define parameters for safe ultrasound delivery; 3) Apply ABI to map  and  oscillations in rat brain with validation usin standard electrophysiology; and 4) Apply and optimize ABI in pig brain (resting-state oscillations, evoked potentials, and induced seizures) compared with gold standard EEG. These aims interweave technology, innovation, modeling, and translation to overcome major obstacles in developing transcranial ABI for humans. They will be embedded in an interactive planning process that brings together wide-ranging ideas, challenging questions, and multidisciplinary expertise in medical imaging, ultrasound technology, neuroengineering, neurosurgery, neuroelectrophysiology, mathematics, psychology, and emergency medicine. The planning process will not only implement face-to-face meetings and site visits, but also social media (ABI.curiosityforall.org) and teleconferencing tools to maximize interaction, facilitate strategic planning, address safety issues, and overcome the Grand Brain Challenge posed by the skull. The project also establishes new collaborations with thought leaders at multiple institutions and industry to consider plans for point-of-care ABI in diverse settings. A safe, portable, and real-time platform designed for humans could transform our understanding of normal brain function and improve management (diagnose, stage, monitor, treat) of a wide variety of neurologic, psychiatric and behavioral disorders (e.g., epilepsy, depression, OCD).