Brain Metabolism Observed at 7 Tesla

Study Overview
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Brief Summary
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The goal is to develop methodology to monitor flux in the citric acid cycle in brain via 13C nuclear magnetic resonance (NMR) spectroscopy at 7 Tesla.

Detailed Description
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The goal is to establish a protocol to 13C-label (from 13C-glucose) several physiological molecules: glucose, lactate, pyruvate and derived compounds. All of these molecules can undergo oxidation in the citric acid cycle. The intent is to study the 13C labeling pattern of these molecules in control and G1D subjects to determine if downstream products (such as 13C bicarbonate or 13C glutamate) due to oxidation in the mitochondria can be detected in brain or in blood by NMR analysis. While inside the instrument, the subjects may also undergo a 7T MR exam to correlate spectroscopy with brain structure.

Official Title
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Brain Metabolism Observed at 7 Tesla in Health and Metabolic Disease.

Conditions
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Glut1 Deficiency Syndrome 1, Autosomal Recessive, Glucose Transporter Type 1 Deficiency Syndrome, Glucose Transporter Protein Type 1 Deficiency Syndrome, Glucose Transport Defect, Glut1 Deficiency Syndrome 1, Glucose Metabolism Disorders, Epilepsy

Intervention / Treatment
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* Device: Magnetic resonance imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adolescents and adults with previously documented diagnosis of Glut1 Deficiency with diagnosis genetically confirmed or confirmed by PET scan of the brain. Ages 16 to 65 Persons with dental fillings, dental crowns, and short (max.4 cm) dental retainer wires can be included. Exclusion Criteria: People or patients with uncontrolled seizure disorder, defined as grand mal (not absence) seizure in the preceding 3 months. Pregnant females will be excluded. A serum or urine pregnancy test will be administered to all females of child bearing potential within 24 hours of administration of the tracer and MRI scan. The pregnancy test will be communicated in person by the study PI. Positive results in subjects 17 years old or younger will be disclosed to parent/guardian only. Subjects with typical implanted orthopedic metal in bone may be considered for inclusion in a 7T scan providing the implant is not within the volume of the radio frequency coil. The PI and the AIRC Medical Director will discuss each case and determine eligibility. Persons with ICD, pacemakers, neurostimulators and other such devices will be excluded. Persons with claustrophobia are excluded. Persons with questionable ferrous implants, bullets, BB's, and shrapnel will be excluded. Subjects who are not fluent in English will be excluded because immediate cooperation and the ability to respond to instructions from the investigators are necessary.

Ages Eligible for Study
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Minimum Age: 16 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adolescents and adults with Glut1 deficiency<br>Adolescents and adults with previously documented diagnosis of Glut1 Deficiency with diagnosis genetically confirmed or confirmed by PET scan of the brain. Ages 16 to 65 Persons with dental fillings, dental crowns, and short (max.4 cm) dental retainer wires can be included. | Device: Magnetic resonance imaging<br>* Medical imaging technique used in radiology to form pictures of the anatomy.<br>* Other names: MRI;|
| Normal healthy adolescents and adults<br>Adolescents or adults in good general health. Ages 16 to 65. Persons with dental fillings, dental crowns, and short (max. 4 cm) dental retainer wires can be included. | Device: Magnetic resonance imaging<br>* Medical imaging technique used in radiology to form pictures of the anatomy.<br>* Other names: MRI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Select metabolite abundance measured at 7Tfield strength | Relative spectral amplitude at equilibrium time point (equilibrium will be defined from the spectra) of the lactate, glucose and bicarbonate spectral peaks arising from infused 13C glucose as measured by magnetic resonance spectroscopy (non contrast brain MRS 7T) | Day 1, immediately after 13 C labeled isotope infusion | 
| Select metabolite abundance measured at 3T field strength | Relative spectral amplitude at equilibrium time point (equilibrium will be defined from the spectra) of the lactate, glucose and bicarbonate spectral peaks arising from infused 13C glucose as measured by magnetic resonance spectroscopy (non contrast brain MRS 3T) | Day 1, immediately after 13 C labeled isotope infusion |