MEASUREMENT OF IN VIVO CEREBRAL METABOLISM BY C13/H1

THE OBJECTIVE OF THIS STUDY IS TO NON-INVASIVELY EXAMINE IN-VIVO CEREBRAL CARBOHYDRATE METABOLISM BY C-13 NUCLEAR MAGNETIC RESONANCE (NMR). THE PURPOSE OF THIS WORK IS TO DEVELOP INSTRUMENTATION FOR C-13 NMR SPECTROSCOPY OF HUMANS TO PURSUE FUNDAMENTAL RESEARCH ON BRAIN BIOCHEMICAL DISORDERS SUCH AS SCHIZOPHRENIA AND TARDIVE DYSKINESIA. THESE STUDIES WILL BE CONDUCTED AT 2.1 TESLA AND 5.0 TESLA SO THAT S/N RATIOS, C-13 T1'S, DECOUPLER EFFICIENCY, NUCLEAROVERHAUSER ENHANCEMENTS (NOE) AND RF HEATING MAY BE COMPARED. WE PLAN TO UTILIZE GLUCOSE, ENRICHED WITH C-13 AT SPECIFIC POSITIONS TO DETERMINE IN-VIVO INTERMEDIARY METABOLISM OF THE BRAIN. THE RELATIVE QUANTITIES AND IDENTITIES OF C-13 LABELED METABOLIC INTERMEDIATES CAN BE FOUND BY CALCULATING THE CHEMICAL SHIFT AND AREA FOR EACH PEAK IN THE C-13 OR H-1NMR SPECTRUM. WE PLAN TO MEASURE THE INCORPORATION OF GLUCOSE CARBONS INTO LACTATE, AND THE EXTENT OF DILUTION OF GLUCOSE CARBONS TRAVERSING THE TRICARBOXYLIC ACID CYCLE WITHTHEIR SUBSEQUENT INCORPORATION INTO OTHER CARBON POOLS OF THE BRAIN, I.E. GLUTAMATE, GLUTAMINE, GABA, AND ALANINE. TECHNIQUES AND INSTRUMENTATION DEVELOPED AS A CONSEQUENCE OF THIS RESEARCH SHOULD BE TRANSFERABLE TO EXISTING "HIGH FIELD" (2.OT) WHOLE BODY CLINICAL IMAGING SYSTEMS FOR PHASE II HUMAN INVESTIGATIONS. FUTURE COMMERCIALIZATION MAY LEAD TO THE DEVELOPMENT OF INSTRUMENTATION FOR WHOLE BODY OR HEADSYSTEMS WITH CENTRAL FIELDS GREATER THAN 4.0 TESLA.