SBIR-STTR Award

The long-term objective of the proposed project is to design a cost-effective, light-weight, integrated, whole- head EEG/NIR brain imaging and data analysis system for non-invasive recording of brain activity in neonates and young children. This system will permit bedside monitoring of immediate at-risk neonates, and early identification and intervention for abnormalities that predict developmental disabilities and cognitive deficits. A dense-array of 128 combined opto-electrodes sitting on the surface of the scalp will simultaneously record brain electrical activity (electroencephalography, EEG), and cerebral blood oxygenation changes (near-infrared spectroscopy, NIRS), providing complementary measures on the timing and location of brain function. For Phase I, the first Specific Aim is to develop a prototype EEG/NIR sensor net for neonates. Source and sensor opto-electrodes will be assembled into a flexible polymer web (building on EGI's existing geodesic net structure used for 128-channel EEG recording). In addition to housing silver-silver chloride electrodes for EEG acquisition, each source opto-electrode will contain miniature dual-wavelength LEDs for transmitting NIR flux into the head and each detector opto-electrode will contain light detectors and pre-amplifiers for measuring recovered NIR flux (the fractional flux changes being related to changes in oxygenated and deoxygenated hemoglobin concentrations). Miniature shielded wires will connect the opto-electrodes to subsystems that either drive modulated currents to the source LEDs or perform analog-to-digital conversion of the EEG and NIR signals. Multiple unique modulation frequencies will make it possible to drive and distinguish all light sources at detectors using FFT demodulation. EEG, NIR, experimental stimuli, and other recorded physiological signals (e.g., EKG, EMG) will be synchronized using EGI's existing Amp Server technology. Through iterative in-house testing, the infant net and system design will be further refined to improve sensor contact, minimize movement artifact, address comfort and stability, and ensure practical usability of the system as a whole. The second Specific Aim is to field-test the prototype system for data integrity, functionality and usability. Simultaneous resting state EEG and NIR data will be collected on 10 neonates within 24 hours of birth through collaboration with the Subcontractor, who has research privileges at a neonatal hospital unit and expertise in neonatal dense-array EEG. The opto-electrode net will be formally evaluated for fit, safety and comfort, including sensor positioning, contact and pressure, and ease of application. EEG data integrity will be assessed by expert review for comparability to resting EEG data previously collected with EGI's standard HCGSN EEG system in terms of signal quality, and noise and movement artifact. NIRS data integrity will be assessed for fall-off in signal recovery with distance from emitters that is consistent with the computational model of optical diffusion, and for the presence of a readily identifiable cardiac pulse. Aim 3 is to define the architecture for a commercially viable integrated EEG/NIR system for infants and the path for developing it within Phase II.

Public Health Relevance:
The goal of this project is to develop the first lightweight device capable of providing real-time spatial and temporal brain imaging information regarding newborn and young infant neural functioning. Such a development would facilitate bedside monitoring of immediate at-risk newborns and offer us the incredible opportunity to identify in very young infants the structural and functional abnormalities that may contribute to later emerging developmental disabilities. Such early identification is vital to the development of early interventions that may mitigate or even preclude the emergence of the disorder.

Public Health Relevance Statement:
Project Narrative The goal of this project is to develop the first lightweight device capable of providing real-time spatial and temporal brain imaging information regarding newborn and young infant neural functioning. Such a development would facilitate bedside monitoring of immediate at-risk newborns and offer us the incredible opportunity to identify in very young infants the structural and functional abnormalities that may contribute to later emerging developmental disabilities. Such early identification is vital to the development of early interventions that may mitigate or even preclude the emergence of the disorder.

NIH Spending Category:
Bioengineering; Brain Disorders; Clinical Research; Mental Health; Neurosciences; Pediatric

Project Terms:
0-11 years old; 0-6 weeks old; AD/HD; ADHD; Address; Ag element; Amplifiers; Analysis, Data; Architecture; Artifacts; Arts; Attention deficit hyperactivity disorder; Attention-Deficit Disorder, Predominantly Hyperactive-Impulsive Type; Autism; Autism, Early Infantile; Autism, Infantile; Autistic Disorder; Automobile Driving; Birth; Blood; Brain; Brain imaging; Cardiac; Cell Communication and Signaling; Cell Signaling; Cerebrum; Child; Child Development Disorders; Child Youth; Children (0-21); Clinical; Cognitive deficits; Collaborations; Complement; Complement Proteins; Computer Programs; Computer Simulation; Computer software; Computerized Models; Computers; Data; Data Analyses; Data Collection; Data Quality; Development; Developmental Disabilities; Devices; Diagnosis; Diffusion; Disease; Disorder; Drivings, Automobile; Dyslexia; ECG; EEG; EKG; Early identification; Early treatment; Electrocardiogram; Electrocardiography; Electrodes; Electroencephalography; Encephalon; Encephalons; Engineering / Architecture; Ensure; Epilepsy; Epileptic Seizures; Epileptics; Frequencies (time pattern); Frequency; Goals; HOSP; Head; Hemoglobin; Hospital Units; Hospitals; Hour; Housing; Human, Child; Hyperactivity Disorder NOS; Hyperactivity Disorder, Predominantly Hyperactive-Impulsive Type; Hyperkinetic Syndrome; IQ Deficit; Infant; Infant Care; Infant, Newborn; Internet; Intervention; Intervention Strategies; Intracellular Communication and Signaling; Kanner's Syndrome; Kentucky; Length of Life; Life; Light; Location; Longevity; MR Imaging; MR Tomography; MRI; Magnetic Resonance Imaging; Magnetic Resonance Imaging Scan; Mathematical Model Simulation; Mathematical Models and Simulations; Measures; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; Models, Computer; Monitor; Morphologic artifacts; Movement; NIR Spectroscopy; NMR Imaging; NMR Tomography; Near-Infrared Spectroscopy; Neonatal; Nervous; Nervous System, Brain; Neurocognitive Deficit; Neurodevelopmental Disability; Neurophysiology - biologic function; Newborn Infant; Newborns; Noise; Nuclear Magnetic Resonance Imaging; Nurseries; Optics; Output; Painless; Parturition; Phase; Photoradiation; Physiologic; Physiologic pulse; Physiological; Polymers; Position; Positioning Attribute; Pressure; Pressure- physical agent; Procedures; Protocol; Protocols documentation; Pulse; Recovery; Research; Rest; Reticuloendothelial System, Blood; Risk; Safety; Scalp; Scalp structure; Seizure Disorder; Signal Transduction; Signal Transduction Systems; Signaling; Silver; Simulation, Computer based; Sleep Disorders; Software; Source; Spectrometry, Near-Infrared; Spectroscopy, Near-Infrared; Stimulus; Structure; Summary Reports; Surface; System; System, LOINC Axis 4; Technology; Testing; Time; Uncertainty; WWW; Weight; Word Blindness; Work; Zeugmatography; analog; attention deficit hyperactive disorder; biological signal transduction; body movement; brain electrical activity; brain visualization; children; commercial application; computational modeling; computational models; computational simulation; computer based models; computer program/software; computerized data processing; computerized modeling; computerized simulation; cost; data integrity; data processing; design; designing; detector; digital; disease/disorder; doubt; driving; epilepsia; epileptiform; epileptogenic; falls; flexibility; hemodynamics; imaging modality; improved; in silico; infant health care; innovate; innovation; innovative; interventional strategy; life span; lifespan; light (weight); miniaturize; neonate; neural; neural function; newborn human (0-6 weeks); non-invasive system; pressure; prototype; public health relevance; relating to nervous system; response; sensor; signal processing; silver chloride electrode; sleep problem; technological innovation; usability; virtual simulation; web; world wide web; youngster

The goal of this SBIR project is to design a cost-effective, lightweight, integrated, whole-head dense-array electroencephalography and near-infrared spectroscopy (dEEG/NIRS) brain imaging and data analysis system for non-invasive recording of brain activity in neonates and young children. This system will permit bedside monitoring of immediate at-risk neonates, and early identification and intervention for abnormalities that predict developmental disabilities and cognitive deficits. A dense array of 128 combined optoelectrodes sitting on the surface of the scalp will simultaneously record brain electrical activity (EEG), and cerebral blood oxygenation changes (NIRS), providing complementary measures of brain function. Having demonstrated feasibility in Phase I with a partial array and single modulated wavelength, the first Specific Aim in Phase II is to extend the approach to complete a commercially viable, whole-head and dual-wavelength dEEG/NIRS acquisition system for infants. The existing design will be modified to use dual-wavelength LED emitters for hemoglobin measurements, with enhanced stability and robustness of the integrated optoelectrodes. New architecture will modulate up to 64 NIR light sources (32 dual-wavelength LEDs) at different frequencies and demodulate signals from up to 96 detectors. NIRS data acquisition software will be refined and further improvements will be made to the integration and synchronization with other acquisition streams, including Net Station EEG, Polygraphic Input Box data (e.g., ECG, EMG), and E-Prime experimental control software. The second Specific Aim is to design commercial, advanced data analysis tools for accurate computation of blood oxygenation changes measured with integrated dEEG/NIRS sensors. This NIRS analysis software will complement EGI's existing EEG processing and source analysis software. The first step will be to implement standard computational tools (based on the modified Beer-Lambert equation) that are used to determine changes in oxy- and deoxy-hemoglobin as measured by recovered NIR signals. Then, the computational parameters will be refined through advanced anatomical infant head modeling, and numerical modeling of the path, scattering, and absorption properties of NIR light through infant head tissues. The third Specific Aim will test and validate the integrated dEEG/NIRS system hardware and software for data integrity, functionality, and usability. Simultaneous dEEG and NIR data will be collected with the complete 128-sensor system during resting state and functional tasks in 30 neonates. The functional data task wil present simple speech and matched non-speech sounds that have previously resulted in individual differences in brain electrical patterns predictive of later dyslxia diagnosis. Outputs from in-house NIRS analysis tools will be cross validated with existing open-source analysis tools (e.g., HomER). Usability of the acquisition and analysis software will be assessed and further refinements made. Finally, commercial user guides for hardware, acquisition software, and analysis software will be prepared to accompany the dEEG/NIRS acquisition and analysis product.

Public Health Relevance:
The goal of this project is to develop the first lightweight device capable of providing real-time spatial and temporal brain imaging information regarding newborn and young infant neural functioning. Such a development would facilitate bedside monitoring of immediate at-risk newborns and offer us the incredible opportunity to identify in very young infants the structural and functional abnormalities that may contribute to later emerging developmental disabilities. Such early identification is vital to the development of early interventions that may mitigate or even preclude the emergence of the disorder.