ABSTRACTThe overarching goal of this project is to optimize validate and implement a revolutionary and safe modalityfor noninvasive functional imaging of neural currents deep in the human brain through the skull atunprecedented spatial and temporal resolution. Transcranial Acoustoelectric Brain Imaging (tABI) is adisruptive technology that exploits pulses of ultrasound (US) to transiently interact with physiologic currentproducing a radiofrequency (RF) signature detected by one or more sensors (e.g. surface electrodes). Byrapidly sweeping the US beam and simultaneously detecting these RF modulations 4D high resolution currentdensity maps are generated. This approach overcomes limitations with electroencephalography (EEG) whichsuffers from poor spatial resolution and inaccuracies due to blurring of electrical signals as they pass throughthe brain and skull and unlike fMRI and PET that measure slow intrinsic signals tABI directly maps fasttime-varying current within a defined brain volume at the mm and ms scales. As a disruptive and scalablemodality for noninvasive human brain imaging tABI offers the following benefits: 1) High spatial resolutiondetermined by the US focus (e.g. 0.3 3 mm); 2) Real-time volumetric imaging of local field potentials andevoked activity; 3) 4D imaging of neural currents from deep brain structures without assuming theconductivity distribution; and 4) Co-registration of neural currents (tABI) with brain structure motion (pulseecho US) and cerebral blood flow (Doppler). Our multidisciplinary team of engineers physicistsneuroscientists psychologists and imagers will overcome the primary challenge of detecting weak interactionsignals through skull at safe US intensities. To demonstrate tABI as a safe and reliable modality for electricalbrain imaging at the mm and ms scales in healthy volunteers we propose to 1) Optimize calibrate andvalidate tABI using established human head and in vivo swine models; 2) Develop and validate the first tABIplatform for functional brain imaging in human subjects; 2a) Assess extraoperative tABI for mapping patientswith intractable epilepsy referred for surgery; and 2b) Assess tABI for mapping somatotopic organization inhealthy volunteers. If successful this project will deliver a safe revolutionary and mobile technology fornoninvasive human brain imaging with the goal of transforming our understanding of brain function and helpdiagnose stage monitor and treat a wide variety of neurologic (e.g. epilepsy Parkinsons) psychiatric (e.g.depression) and behavioral (e.g. OCD) disorders.