ABSTRACT The overarching goal of this project is to optimize, validate and implement a revolutionary and safe modality for noninvasive functional imaging of neural currents deep in the human brain through the skull at unprecedented spatial and temporal resolution. Transcranial Acoustoelectric Brain Imaging (tABI) is a disruptive technology that exploits pulses of ultrasound (US) to transiently interact with physiologic current, producing a radiofrequency (RF) signature detected by one or more sensors (e.g., surface electrodes). By rapidly sweeping the US beam and simultaneously detecting these RF modulations, 4D high resolution current density maps are generated. This approach overcomes limitations with electroencephalography (EEG), which suffers from poor spatial resolution and inaccuracies due to blurring of electrical signals as they pass through the brain and skull, and, unlike fMRI and PET that measure slow “intrinsic” signals, tABI directly maps fast time-varying current within a defined brain volume at the mm and ms scales. As a disruptive and scalable modality for noninvasive human brain imaging, tABI offers the following benefits: 1) High spatial resolution determined by the US focus (e.g., 0.3 – 3 mm); 2) Real-time, volumetric imaging of local field potentials and evoked activity; 3) 4D imaging of neural currents from deep brain structures without assuming the conductivity distribution; and 4) Co-registration of neural currents (tABI) with brain structure, motion (pulse echo US) and cerebral blood flow (Doppler). Our multidisciplinary team of engineers, physicists, neuroscientists, psychologists, and imagers will overcome the primary challenge of detecting weak interaction signals through skull at safe US intensities. To demonstrate tABI as a safe and reliable modality for electrical brain imaging at the mm and ms scales in healthy volunteers, we propose to 1) Optimize, calibrate, and validate tABI using established human head and in vivo swine models; 2) Develop and validate the first tABI platform for functional brain imaging in human subjects; 2a) Assess extraoperative tABI for mapping patients with intractable epilepsy referred for surgery; and 2b) Assess tABI for mapping somatotopic organization in healthy volunteers. If successful, this project will deliver a safe, revolutionary and mobile technology for noninvasive human brain imaging with the goal of transforming our understanding of brain function and help diagnose, stage, monitor and treat a wide variety of neurologic (e.g., epilepsy, Parkinson’s), psychiatric (e.g., depression) and behavioral (e.g., OCD) disorders.

PROJECT NARRATIVE Our vision is to develop the first safe, real-time and high resolution system for mapping electricity in the human brain. Transcranial Acoustoelectric Brain Imaging (tABI) would transform our understanding of normal brain function and help diagnose, monitor, and treat a wide variety of neurologic, psychiatric, and behavioral disorders. This collaborative project will assemble a world-class multidisciplinary team to overcome major challenges with detecting weak signals in the brain to deliver a revolutionary and mobile imaging tool for human neuroscience and beyond.