SBIR-STTR Award

EsperImage, a startup company out of Washington University (WUSTL), will develop efficient and flexible data registration and modeling procedures to complement their high fidelity, wearable, optical technology that transcends limitations of both previous optical neuroimaging and functional magnetic resonance imaging (fMRI) tools to provide naturalistic brain imaging in adults and children. A neurodevelopmental disorder affecting 1/36 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 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, including a lack of automatable data registration and modeling such as those proposed herein. This Phase-I STTR project will develop commercialization-ready, robust, & efficient data registration and modeling tools for WHD-DOT devices that match performance of fiber-based HD-DOT for use in pediatric studies of neurodevelopmental disorders. Long Term Impact: The data registration and WHD systems together will enable a better understanding of disease mechanisms as well as monitor response to therapy in the developing brain. The Aim 1 goal is to develop flexible 2D-camera-based photogrammetric array-anatomy registration. The Aim 2 goal will be to develop photogrammetric atlas-derived anatomical models. We will validate the registration and modeling methods in healthy adults and autistic/non-autistic children to establish feasibility through mapping distributed brain activity in untethered participants. This will establish an essential data registration and modeling product for WHD-DOT commercialization development in a follow-up Phase-II proposal.

Public Health Relevance Statement:
Narrative: Brain imaging with MRI machines provides non-invasive access to the neural basis of development, degeneration, and disease of the brain. However, the logistics of MRI are ill-suited to many applications in children. This grant will develop a flexible and efficient method for data registration and modeling for high-performance wearable high-density diffuse optical tomography systems and validate it within both adults and children. Terms: <0-11 years old; 21+ years old; 3-D; 3-Dimensional; 3D; ASD; Active Follow-up; Adult; Adult Human; Affect; Algorithms; Anatomic Models; Anatomic Sites; Anatomic structures; Anatomical Models; Anatomy; Array tomography; Artifacts; Atlases; Autism; Autistic Disorder; BRAIN initiative; Behavioral; Behavioral Symptoms; Brain; Brain Diseases; Brain Disorders; Brain Mapping; Brain Nervous System; Brain Research through Advancing Innovative Neurotechnologies initiative; Brain imaging; Cell Communication and Signaling; Cell Phone; Cell Signaling; Cellular Phone; Cellular Telephone; Child; Child Development; Child Youth; Childhood; Children (0-21); Cognitive; Communication; Complement; Complement Proteins; Data; Development; Devices; Disease; Disorder; Early Diagnosis; Early Infantile Autism; Early Intervention; Encephalon; Encephalon Diseases; Environment; Evaluation; Eye; Eyeball; Fiber; Fiber Optics; Functional MRI; Functional Magnetic Resonance Imaging; General Population; General Public; Goals; Grant; Hair; Head; IRB; IRBs; Image; Imaging Device; Imaging Instrument; Imaging Tool; Impairment; Infant; Infant and Child Development; Infantile Autism; Institutional Review Boards; Intracellular Communication and Signaling; Intracranial CNS Disorders; Intracranial Central Nervous System Disorders; Kanner's Syndrome; Legal patent; Licensing; Light; Literature; Location; Logistics; Loudness; MR Imaging; MR Tomography; MRI; MRIs; Magnetic Resonance Imaging; Maps; Market Research; Measurement; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; Methodology; Methods; Mobile Phones; Modeling; Modernization; Monitor; Morphologic artifacts; Motion; Motor; NMR Imaging; NMR Tomography; Neurodevelopmental Disorder; Neurological Development Disorder; Noise; Nuclear Magnetic Resonance Imaging; Optics; Outcome; Parents; Participant; Patents; Performance; Phase; Phenotype; Photogrammetry; Photoradiation; Play; Predisposition; Procedures; Process; Prognosis; Protocol; Protocols documentation; Reporting; Resolution; Role; STTR; Scalp; Scalp structure; Sensory; Shapes; Signal Transduction; Signal Transduction Systems; Signaling; Small Business Technology Transfer Research; Social Development; Standardization; Surface; Susceptibility; System; Technology; Toddler; Transcend; Translations; Universities; Validation; Washington; Zeugmatography; active followup; adulthood; autism spectral disorder; autism spectrum disorder; autistic; autistic individuals; autistic people; autistic spectrum disorder; awake; biological signal transduction; brain visualization; cognitive capacity; commercial application; commercialization; commercialization readiness; complementation; density; developmental; diffuse optical tomography; dyadic interaction; early detection; eye tracking; fMRI; fNIRS; flexibility; flexible; follow up; follow-up; followed up; followup; functional near infrared spectroscopy; gaze; iPhone; image construction; image generation; image reconstruction; imaging; improved; improved outcome; individuals on the autism spectrum; individuals on the spectrum; individuals with ASD; individuals with autism; individuals with autism spectrum disorder; innovate; innovation; innovative; instrument; interest; kids; neural; neural imaging; neuro-imaging; neurodevelopmental disease; neuroimaging; neurological imaging; non-human primate; nonhuman primate; optic imaging; optical; optical imaging; parent; pediatric; people on the autism spectrum; people with ASD; people with autism; people with autism spectrum disorder; repetitive behavior; resolutions; response; response to therapy; response to treatment; sensor; skill acquisition; skill development; skills; smart phone; smartphone; social; social attachment; social bonding; social communication impairment; social role; technological innovation; therapeutic response; therapy response; three dimensional; tomography; tool; translation; treatment response; treatment responsiveness; treatment strategy; validations; visual motor; visual tracking; visual-motor integration; visuomotor; wearable; wearable device; wearable electronics; wearable system; wearable technology; wearable tool; wearables; youngster