R01NS122119

Development of Quantitative Optical Tools to Continuously Monitor Cerebral Autoregulation, Blood Flow, Oxygenation, and Inflammation During Pediatric Extracorporeal Life Support - Extracorporeal Membrane Oxygenation (ECMO) is a form of cardiopulmonary bypass which provides days to weeks of life-saving support to critically ill children and adults whose illness is progressing despite maximal conventional therapies. Use of ECMO is expanding rapidly and it has supported >71,000 children worldwide.

Advances in ECMO have allowed more children to survive an otherwise fatal illness, however neurological injury reduces survival by 50-60% and leads to significant long-term neurologic morbidity. Only half of ECMO survivors have normal neurobehavioral outcomes.

The underlying disease and ECMO may both disrupt cerebral autoregulatory mechanisms and cause neuroinflammation, which may also disrupt autoregulation. Disrupted cerebral autoregulation predisposes the brain to hemorrhagic or ischemic injury via excessive or inadequate perfusion, yet it is not monitored during ECMO.

Current clinical tools do not predict neurological injury, greatly inhibiting the development of neuroprotective protocols. Specifically, there is no monitor to continuously assess the state of cerebral autoregulation, forcing clinicians to rely on imperfect systemic surrogates that may not reflect risks of impending neurological injury.

The long-term goal of this research is to develop continuous non-invasive bedside monitors for critically ill patients. The primary goals of this proposal are to (1) test the hypothesis that continuous point-of-care optical monitoring of cerebral autoregulation can predict neurologic injury after the first 48 hours of ECMO and (2) demonstrate that optically measured indices of cerebral autoregulation are associated with neuroinflammatory biomarkers in serial blood samples throughout ECMO.

A pilot study led by the PI has demonstrated the feasibility of using advanced non-invasive optical monitors to assess cerebral autoregulation and cerebral perfusion in pediatric ECMO patients. Our ongoing pilot study has shown disrupted autoregulation indices correlate with neurological injury found on post-ECMO imaging.

This proposal will utilize diffuse optics to longitudinally monitor cerebral autoregulation and inflammation throughout ECMO in a large pediatric population (0-18 y.o., N=125). In Aim 1, we will demonstrate that alterations in optical metrics of cerebral autoregulation during ECMO predict neurological injury found on intra-ECMO CT. In Aim 2, we will demonstrate that optical metrics of cerebral autoregulation measure the temporal course of neuroinflammation, as evidenced by biomarkers in lab-based blood assays.

If successful, the work of this interdisciplinary team of physical scientists, clinicians, and neuroscientists will establish the value of continuous quantitative optical monitoring of cerebral autoregulation to prospectively identify periods of high risk of injury during ECMO. These results will enable the development of brain-focused cardio-pulmonary bypass protocols (e.g., blood pressure titration) to reduce the rate of neurologic injury and associated mortality and morbidity in ECMO patients.

The University Of Texas Southwestern Medical Center

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM; RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS; RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS; IMPROVED METHODS OF DISEASE PREVENTION; NEW METHODS OF DIAGNOSIS AND TREATMENT; DRUG DEVELOPMENT; DEVELOPMENT OF NEURAL DEVICES; CLINICAL TRIALS; AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH; SYNAPSE FORMATION, FUNCTION, AND PLASTICITY; LEARNING AND MEMORY; CHANNELS, TRANSPORTERS, AND PUMPS; CIRCUIT FORMATION AND MODULATION; BEHAVIORAL AND COGNITIVE NEUROSCIENCE; SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION; NEUROENDOCRINE SYSTEMS; SLEEP AND CIRCADIAN RHYTHMS; AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE; TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM; NEURODEGENERATIVE DISORDERS; MOVEMENT DISORDERS; BRAIN TUMORS; CONVULSIVE DISORDERS; INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM; IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS; DISORDERS RELATED TO SLEEP; AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE THE NEUROSCIENCE WORKFORCE, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM; TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT; TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT; AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM; TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS; TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS; TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT; AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.853 - Extramural Research Programs in the Neurosciences and Neurological Disorders

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

Dallas, Texas 753907208 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 368% from $682,467 to $3,193,564.