Non-invasive Clinical Imaging of Cerebral Metabolism Following Brain Injury Using 13C Magnetic Resonance Spectroscopy.

Study Overview
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Brief Summary
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Despite the decline in fatal traumatic brain injury (TBI) incidence in recent years, TBI morbidity remains a public health challenge and is the leading cause of disability in the United States. Detailed knowledge of the metabolic alterations following TBI will provide a significant advancement to our understanding of the hypometabolic response to TBI, which is key information for the future development and testing of novel therapeutic interventions that by-pass or compensate for the metabolic dysfunction. The goal of this study is to determine the clinical utility of in vivo 13C MRS to identify specific metabolic alterations following TBI. We hypothesize that following TBI, metabolic pathways are altered causing an incomplete oxidative of glucose in neurons and astrocytes resulting in a decrease in cerebral metabolism.

Detailed Description
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Despite the decline in fatal traumatic brain injury (TBI) incidence in recent years, TBI morbidity remains a public health challenge and is the leading cause of disability in the United States To combat these effects, new research is needed to identify mechanisms of injury that will lead to potential targets for therapeutic interventions that improve neurological outcome. One promising area of research is the cerebral metabolic dysfunction following TBI. Studies of post-traumatic cerebral metabolism have shown that cerebral metabolic rate of glucose (CMRglc) decreases for a period of days, weeks or months after injury with the duration and degree of hypometabolism correlating to level of consciousness and a strong predictor of long-term neurological outcome. However, specific changes in intermediary carbohydrate metabolic pathways have not yet been identified. In addition, the role of astrocyte metabolism in the post-injury metabolism has not been studied. This study uses in vivo 13C magnetic resonance spectroscopy (MRS) at 3 Tesla, a novel method in the clinical study of TBI, to non-invasively study the metabolic fate and flux of glucose (metabolized in both neurons and astrocytes) and acetate (metabolized in astrocytes) through metabolic pathways during the hypometabolic period.

Official Title
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Non-invasive Clinical Imaging of Cerebral Metabolism Following Brain Injury Using 13C Magnetic Resonance Spectroscopy

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Diagnostic Test: 13C magnetic resonance spectroscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will be at least 18 years of age without gender or ethnic restrictions. Severe accidental TBI defined as the lowest post-resuscitation GCS < 8 prior to administration of sedatives or paralytics. Eligibility for MRI per routine screening checklist. Exclusion Criteria: History of neurosurgical intervention, excluding the placement of ventriculostomy shunt History of a prior known brain injury with associated loss of consciousness. History of a known neurological disorder prior to qualifying injury. History of psychiatric disorder. History of diabetes or current unstable serum glucose level. Renal insufficiency or known history of kidney disease. Known contraindication to MRI such as, pacemaker, pregnancy, and/or other non-MR compatible implanted device.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>13C Magnetic resonance (MR) spectroscopy. | Diagnostic Test: 13C magnetic resonance spectroscopy<br>* acquisition of 13C MR spectroscopy in the brain<br>* Other names: 13C MRS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of 13C Enriched Cerebral Metabolites | Direct detection, localized in vivo 13C MRS will be used to measure the 13C enrichment of glutamate and glutamine following an infusion of 30% isotopically enriched [1-13C] glucose and [1, 2-13C2] acetate. | 5 years |