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Principal Investigator: Tsang-Wei Tu
Organization: HOWARD UNIVERSITY
Fiscal Year: 2024
Award: $377,376
Funding agency: National Institute of Neurological Disorders and Stroke
PROJECT SUMMARY
Traumatic brain injury (TBI) represents a major public health concern in the United States. TBI can result in
long-term neurological complications, including neurodegeneration, behavioral dysfunction, depression and
epilepsy that seriously affect patient quality-of-life. Brain glucose utilization has been found decreased in 60%
of patients with chronic TBI and is one of the prognostic indicators for the long-term outcome of TBI. Both
animal and human studies have identified that the neurovascular uncoupling between cerebral blood flow
(CBF) and brain tissue energy demands is a key factor for cerebral metabolic crisis in the TBI brain. The
neurovascular uncoupling results in energy mismatch that disrupts normal neuroglial function and arrests
repairing process. Despite numerous clinical trials on potential therapies, there is no U.S. Food and Drug
Administration approved drug therapy for the treatment of TBI. One of the reason clinical trials failed is due to
the inability that can accurately evaluate the region-specific perturbations of brain glucose metabolism and
determine if a treatment can restore neurovascular coupling in the TBI brain. Existent glucose measuring
techniques, including microdialysis, continuing blood glucose monitoring, spectroscopy, or positron emission
tomography (PET) which uses tracer radioisotopes, provide insufficient resolution to determine region-specific
glucose utilization in the brain. In this proposal, we determine to assess the utility of a novel MRI-based
Chemical Exchange Saturation Transfer (CEST) imaging, to provide the needed high-resolution for measuring
region-specific metabolism for TBI. The glucose detecting CEST MRI (glucoCEST) measures brain glucose by
detecting the exchangeable proton signals of glucose without using radioisotopes and generates glucose
mapping in a resolution >100 times higher than PET scans. Our preliminary and published data have
demonstrated that glucoCEST may be feasible to detect the delayed hypometabolism of diffuse TBI in rats. We
propose to combine high-resolution glucoCEST and the Dynamic Contrast Enhanced (DCE) perfusion MRI for
concomitant CBF measurements to identify the neurovascular coupling state following TBI over time. Our aims
are designed to (1) Identify the contrast mechanism of in vivo glucoCEST in the TBI brain to enhance the
sensitivity and specificity of glucoCEST with advanced acquisition scheme and analytical models, (2)
Characterize perturbations in brain glucose metabolism and perfusion deficits in the TBI brain, and (3)
Demonstrate the potential application of the dual-modality CEST-DCE MRI to noninvasively monitor the
treatment effects of a clinically-recommended intervention for TBI. Overall, these studies will provide a strong
technical and scientific foundation to move the field forward in utilization of advanced MRI for personalized
care in the clinical arena and determine the best treatment strategy for the brain injured patients.
Terms: <AD dementia><Acceleration><Acquired brain injury><Acute><Affect><Alzheimer Type Dementia><Alzheimer disease dementia><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Disease><Alzheimers Dementia><Animals><Area><Assay><Autoradiography><Behavioral><Bioassay><Bioenergetics><Biological Assay><Blood - brain barrier anatomy><Blood Glucose><Blood Sugar><Blood-Brain Barrier><Body Tissues><Brain><Brain Injuries><Brain Nervous System><Brain Trauma><Brain region><Cause of Death><Cell Communication and Signaling><Cell Signaling><Cerebrovascular Circulation><Cerebrum><Chemicals><Chronic><Clinical><Clinical Trials><Common Rat Strains><D-Glucose><DWI (diffusion weighted imaging)><DWI-MRI><Data><Degenerative Neurologic Disorders><Depakote><Depakote ER><Development><Dextrose><Diagnosis><Diffuse><Diffusion MRI><Diffusion Magnetic Resonance Imaging><Diffusion Weighted MRI><Diffusion weighted imaging><Diffusion-weighted Magnetic Resonance Imaging><Disease><Disorder><Divalproex><Drug Therapy><Dysfunction><Encephalon><Energy Expenditure><Energy Metabolism><Epilepsy><Epileptic Seizures><Epileptics><Event><Failure><Food and Drug Administration><Foundations><Functional disorder><Glucose><Goals><H+ element><Head><Hemato-Encephalic Barrier><Human><Hydrogen Ions><Hypoxia><Hypoxic><Image><Image Enhancement><Imaging Device><Imaging Instrument><Imaging Tool><Immunohistochemistry><Immunohistochemistry Cell/Tissue><Immunohistochemistry Staining Method><Impairment><Injury><Intermediary Metabolism><Intervention><Intervention Strategies><Intracellular Communication and Signaling><Li+ element><Lithium><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Maps><Measures><Mechanics><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Mental Depression><Metabolic><Metabolic Diseases><Metabolic Disorder><Metabolic Processes><Metabolism><Methodology><Microdialysis><Modality><Modeling><Modern Man><Molecular><Mood stabilizers><NMR Imaging><NMR Tomography><Nerve Degeneration><Nerve Impulse Transmission><Nerve Transmission><Nervous System Degenerative Diseases><Neural Degenerative Diseases><Neural degenerative Disorders><Neurodegenerative Diseases><Neurodegenerative Disorders><Neurologic><Neurologic Degenerative Conditions><Neurologic outcome><Neurological><Neurological outcome><Neuron Degeneration><Neuronal Transmission><Non-Invasive Detection><Noninvasive Detection><Nuclear Magnetic Resonance Imaging><Outcome><Oxygen Deficiency><PET><PET Scan><PET imaging><PETSCAN><PETT><Pathology><Patients><Patients with traumatic brain injury><Perfusion><Pharmacotherapy><Phase><Physiopathology><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Precision care><Primary Senile Degenerative Dementia><Process><Prognosis><Protons><Public Health><Publishing><QOL><Quality of life><Rad.-PET><Radioactive Isotopes><Radioautography><Radioisotopes><Radionuclides><Rat><Rats Mammals><Rattus><Recommendation><Resolution><Risk><Scheme><Seizure Disorder><Sensitivity and Specificity><Severities><Signal Transduction><Signal Transduction Systems><Signaling><Source><Spectroscopy><Spectrum Analyses><Spectrum Analysis><TBI Patients><TBI therapy><TBI treatment><Techniques><Thesaurismosis><Time><Tissues><Tracer><Translating><Traumatic Brain Injury><Treatment Efficacy><USFDA><United States><United States Food and Drug Administration><Valproic Acid><Zeugmatography><analytical method><axon damage><axon injury><axon signaling><axon-glial signaling><axonal damage><axonal injury><axonal signaling><biological signal transduction><blood flow in brain><blood flow measurement><bloodbrain barrier><brain blood circulation><brain blood flow><brain damage><brain metabolism><brain tissue><brain-injured><cerebral><cerebral blood flow><cerebral circulation><cerebrocirculation><cerebrovascular blood flow><clinical relevance><clinically relevant><contrast enhanced><dMRI><degenerative diseases of motor and sensory neurons><degenerative neurological diseases><depression><design><designing><determine efficacy><develop therapy><developmental><diffusion tensor imaging><disability><drug treatment><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><epilepsia><epileptogenic><evaluate efficacy><examine efficacy><glia signaling><glial signaling><glucometer><glucose metabolism><glucose meter><glucose monitor><imaging><improved><in vivo><individualized care><individualized patient care><injuries><injury to tissue><intervention development><intervention efficacy><interventional strategy><mechanic><mechanical><metabolism disorder><nerve signaling><neural degeneration><neural signaling><neuro-vascular><neuro-vascular coupling><neurodegeneration><neurodegenerative><neurodegenerative illness><neurological degeneration><neuronal degeneration><neuronal signaling><neurotransmission><neurotransmitter release><neurovascular><neurovascular coupling><non-invasive imaging><non-invasive monitor><noninvasive imaging><noninvasive monitor><novel><pathophysiology><personalized care><personalized patient care><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><primary degenerative dementia><prognostic indicator><public health relevance><repair><repaired><resolutions><senile dementia of the Alzheimer type><therapeutic efficacy><therapy development><therapy efficacy><timeline><tissue injury><tool><traumatic brain damage><traumatic brain injury patients><traumatic brain injury therapy><traumatic brain injury treatment><treatment development><treatment effect><treatment strategy>