SBIR-STTR Award

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 establish a full-head WHD-DOT product for commercialization development in a follow-up Phase-II proposal.

Public Health Relevance Statement:


Project 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 high-performance wearable high- density diffuse optical tomography system and validate it within both adults and children.

Project Terms:
Adult; 21+ years old; Adult Human; adulthood; Affect; Behavioral Symptoms; Brain; Brain Nervous System; Encephalon; Brain Diseases; Brain Disorders; Encephalon Diseases; Intracranial CNS Disorders; Intracranial Central Nervous System Disorders; Brain Mapping; Child; 0-11 years old; Child Youth; Children (0-21); youngster; Child Development; Infant and Child Development; Communication; Disease; Disorder; Environment; Eye; Eyeball; Fiber Optics; Goals; Gold; Grant; Hair; Head; Infant; Literature; Magnetic Resonance Imaging; MR Imaging; MR Tomography; MRI; MRIs; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; NMR Imaging; NMR Tomography; Nuclear Magnetic Resonance Imaging; Zeugmatography; Maps; Market Research; Methods; Methodology; Motion; Neurosciences; Noise; optical; Optics; Parents; Patents; Legal patent; Patients; Phenotype; Play; Rest; social role; Role; Scalp; Scalp structure; Cell Communication and Signaling; Cell Signaling; Intracellular Communication and Signaling; Signal Transduction Systems; Signaling; biological signal transduction; Signal Transduction; Social Development; Technology; tomography; Translations; Universities; Washington; Morphologic artifacts; Artifacts; autistic children; children with ASD; children with autism; children with autism spectrum disorder; base; density; Loudness; detector; improved; Brain imaging; brain visualization; Phase; Susceptibility; Predisposition; Fiber; pediatric; Childhood; awake; Individual; non-human primate; nonhuman primate; Logistics; Early Intervention; Shapes; instrument; Combs; Comb animal structure; Functional MRI; fMRI; Functional Magnetic Resonance Imaging; Protocol; Protocols documentation; Sensory; Source; System; Transcend; interest; gaze; dyadic interaction; early detection; Early Diagnosis; Performance; eye tracking; visual tracking; neural; relating to nervous system; skills; neuro-imaging; neurological imaging; neuroimaging; Toddler; technological innovation; General Public; General Population; Devices; Reporting; Morphologic Finding; morphologic criteria; morphologic signature; morphological criteria; morphological signature; Physical shape; social; social bonding; social attachment; Modeling; response; diffuse optical tomography; Autism; Autistic Disorder; Early Infantile Autism; Infantile Autism; Kanner's Syndrome; autistic spectrum disorder; autism spectrum disorder; Detection; Imaging Instrument; Imaging Tool; Imaging Device; Motor; Resolution; Cognitive; Small Business Technology Transfer Research; STTR; Validation; Monitor; follow-up; Active Follow-up; active followup; follow up; followed up; followup; Development; developmental; Neurodevelopmental Disorder; Neurological Development Disorder; Behavioral; Image; imaging; design; designing; social communication impairment; Outcome; visual motor; visuomotor; aged; Coupling; innovation; innovate; innovative; Impairment; skill acquisition; skill development; commercial application; commercialization; treatment response; response to therapy; response to treatment; therapeutic response; therapy response; treatment strategy; Institutional Review Boards; IRB; IRBs; cognitive capacity; BRAIN initiative; Brain Research through Advancing Innovative Neurotechnologies initiative; imaging system; improved outcome; repetitive behavior; individuals with autism spectrum disorder; autistic individuals; individuals with ASD; individuals with autism; people with ASD; people with autism; people with autism spectrum disorder; Prognosis; functional near infrared spectroscopy; fNIRS

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 establish a full-head WHD-DOT product for commercialization development in a follow-up Phase-II proposal.

Public Health Relevance Statement:


Project 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 high-performance wearable high- density diffuse optical tomography system and validate it within both adults and children.

Project Terms:
21+ years old; Adult Human; adulthood; Adult; Affect; Behavioral Symptoms; Brain; Brain Nervous System; Encephalon; Brain Diseases; Brain Disorders; Encephalon Diseases; Intracranial CNS Disorders; Intracranial Central Nervous System Disorders; Brain Mapping; Child; 0-11 years old; Child Youth; Children (0-21); kids; youngster; Child Development; Infant and Child Development; Communication; Disease; Disorder; Environment; Eye; Eyeball; Fiber Optics; Goals; Grant; Hair; Head; Infant; Literature; Magnetic Resonance Imaging; MR Imaging; MR Tomography; MRI; MRIs; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; NMR Imaging; NMR Tomography; Nuclear Magnetic Resonance Imaging; Zeugmatography; Maps; Market Research; Methods; Methodology; Motion; Neurosciences; Noise; Optics; optical; Parents; parent; Legal patent; Patents; Patients; Phenotype; Play; Rest; Role; social role; Scalp structure; Scalp; Signal Transduction; Cell Communication and Signaling; Cell Signaling; Intracellular Communication and Signaling; Signal Transduction Systems; Signaling; biological signal transduction; Social Development; Technology; tomography; Translations; translation; Universities; Washington; Artifacts; Morphologic artifacts; children with ASD; children with autism; children with autism spectrum disorder; autistic children; density; Loudness; detector; improved; brain visualization; Brain imaging; Specified; Specific qualifier value; Phase; Susceptibility; Predisposition; Fiber; pediatric; Childhood; awake; Individual; non-human primate; nonhuman primate; Licensing; Logistics; Early Intervention; Shapes; instrument; Functional Magnetic Resonance Imaging; Functional MRI; fMRI; Protocols documentation; Protocol; Sensory; Source; System; Transcend; interest; gaze; dyadic interaction; Early Diagnosis; early detection; Performance; visual tracking; eye tracking; neural; skills; neuroimaging; neural imaging; neuro-imaging; neurological imaging; Toddler; technological innovation; General Population; General Public; Devices; Reporting; Physical shape; Morphologic Finding; morphologic criteria; morphologic signature; morphological criteria; morphological signature; social; social attachment; social bonding; Modeling; response; diffuse optical tomography; autism spectrum disorder; Autism; Autistic Disorder; Early Infantile Autism; Infantile Autism; Kanner's Syndrome; autistic spectrum disorder; Detection; Imaging Device; Imaging Instrument; Imaging Tool; Motor; Resolution; resolutions; Cognitive; Small Business Technology Transfer Research; STTR; Validation; validations; Monitor; follow-up; Active Follow-up; active followup; follow up; followed up; followup; Development; developmental; Neurodevelopmental Disorder; Neurological Development Disorder; neurodevelopmental disease; Behavioral; Image; imaging; designing; design; social communication impairment; Outcome; visuomotor; visual motor; aged; Coupling; innovate; innovative; innovation; Impairment; skill development; skill acquisition; commercial application; optical fiber; commercialization; response to therapy; response to treatment; therapeutic response; therapy response; treatment response; treatment strategy; IRB; IRBs; Institutional Review Boards; cognitive capacity; Brain Research through Advancing Innovative Neurotechnologies initiative; BRAIN initiative; imaging system; improved outcome; repetitive behavior; autistic individuals; individuals with ASD; individuals with autism; people with ASD; people with autism; people with autism spectrum disorder; individuals with autism spectrum disorder; Prognosis; functional near infrared spectroscopy; fNIRS; commercialization readiness