Project Summary: EsperImage, a startup company out of Washington University (WUSTL), will develop high fidelity, wearable, optical technology that transcends limitations of both previous optical neuroimaging and magnetic resonance imaging (MRI) tools to provide naturalistic brain imaging in adults and children. A neurodevelopmental disorder affecting 1/54 children in the general population, autism spectrum disorder (ASD) presents highly heterogeneous phenotypes; however, core features are impaired development of social-communicative skills plus repetitive behaviors and restricted interests. Additionally, early difficulties with visuo-motor integration and motor imitation may be strongly associated with impairments of social communication widely reported in individuals with ASD. Because early interventions in toddlers with ASD have been proven to result in improved outcomes, innovative methods for early detection of the alterations in brain function underlying ASD prior to manifestation of behavioral symptoms are necessary to advance treatment strategies and improve prognoses. Current brain mapping methods such as functional magnetic resonance imaging (fMRI) offer promising sensitivity yet pose significant methodological challenges in studies of awake, interacting, and moving children due to the loud, constraining environment and susceptibility to motion-induced artifacts. Optical neuroimaging provides a potential surrogate for fMRI. However, image quality with traditional optical technology, functional near infrared spectroscopy (fNIRS), systems had been lacking in comparison to the gold standard of fMRI. Development of high-density diffuse optical tomography (HD-DOT), a tomographic version of fNIRS, has dramatically improved image quality, and maps sensory, motor, and cognitive networks with fidelity comparable to fMRI throughout the outer 1 cm of the cortex. Despite these advances, application of HD-DOT to naturalistic studies in children has been limited by large opto-electronic consoles and bulky fiber optics. Several wearable fiber-less fNIRS instruments are becoming available commercially, but all have multiple deficits - either lower resolution, stronger image distortions, smaller fields of view, or less signal to noise than proposed herein. This Phase-I STTR project will develop a commercialization-ready WHD-DOT device that matches performance of fiber-based HD-DOT for use in pediatric studies including on neurodevelopmental disorders. Long Term Impact: The WHD-DOT imaging systems will enable neuroscience to better understand the mechanisms of disease as well as monitor response to therapy in the developing brain. The goal of Aim 1 is to develop a robust modular scalable WHD-DOT system. The goal of Aim 2 will be to validate the WHD system in healthy adults and in children both typical developing and those with ASD. Validation will establish feasibility through mapping distributed brain activity in untethered adults and children. This will...