ABSTRACTThe overarching goal of this project is to develop validate and implement a new modality for noninvasivefunctional imaging of neural currents deep in the human brain through the skull at unprecedented spatial andtemporal resolution. Transcranial Acoustoelectric Brain Imaging (tABI) is a disruptive technology that exploits anultrasound (US) beam to transiently interact with physiologic current producing a radiofrequency signaturedetected by one or more surface electrodes. By rapidly sweeping the US beam and simultaneously detectingthe AE modulations 4D current density images are generated. This approach overcomes limitations withelectroencephalography (EEG) which suffers from poor spatial resolution and inaccuracies due to blurring ofelectrical signals as they pass through the brain and skull and unlike fMRI and PET that measure slow intrinsicsignals tABI directly maps fast time-varying current within a defined brain volume at the mm and ms scales. Asa disruptive modality for noninvasive human brain imaging tABI offers the following benefits: 1) High spatialresolution determined by the US focus (0.5 3 mm); 2) Real-time volumetric imaging of local field potentialsand evoked 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 and motion (pulseecho US) and cerebral blood flow (Doppler). Our multidisciplinary team of engineers neuroscientistspsychologists and imagers will overcome the grand challenge of detecting the weak AE interaction signalthrough the human skull and demonstrate a safe revolutionary modality for electrical brain imaging at the mmand ms scales in healthy volunteers. 1) Develop next-generation integrated platform for tABI of the human brainthrough skull; 2) Optimize calibrate and validate tABI using human head and in vivo swine models; 3) Assessextraoperative tABI for mapping patients with intractable epilepsy referred for surgery; and 4) Assessperformance of tABI for mapping somatotopic organization in healthy volunteers. If successful this project willdeliver a safe revolutionary and mobile modality for noninvasive human brain imaging that would transform ourunderstanding 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.