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Am J Physiol Endocrinol Metab 273: E1216-E1227, 1997;
0193-1849/97 $5.00
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Vol. 273, Issue 6, E1216-E1227, December 1997

SPECIAL COMMUNICATION
Determination of cerebral glucose transport and metabolic kinetics by dynamic MR spectroscopy

P. C. M. Van Zijl1, D. Davis1, S. M. Eleff1,2, C. T. W. Moonen3, R. J. Parker4, and J. M. Strong4

Johns Hopkins University Medical School, Departments of 1 Radiology and 2 Anesthesiology and Critical Care, Baltimore 21205; 3 National Institutes of Health, In Vivo Nuclear Magnetic Resonance Research Center, Biomedical Engineering and Instrumentation Program, National Center for Research Resources, Bethesda 20892; 4 Food and Drug Administration, Center for Drug Evaluation and Research, Office of Research Resources, Division of Clinical Pharmacology, Rockville, Maryland 20850; and 3 Resonance Magnetique des Systemes Biologique, Unité Mixte de Recherche 5536, Centre National de la Recherche Scientifique, Université Victor Segalen 2, F-33076 Bordeaux Cedex, France

A new in vivo nuclear magnetic resonance (NMR) spectroscopy method is introduced that dynamically measures cerebral utilization of magnetically labeled [1-13C]glucose from the change in total brain glucose signals on infusion. Kinetic equations are derived using a four-compartment model incorporating glucose transport and phosphorylation. Brain extract data show that the glucose 6-phosphate concentration is negligible relative to glucose, simplifying the kinetics to three compartments and allowing direct determination of the glucose-utilization half-life time [t1/2 = ln2/(k2 + k3)] from the time dependence of the NMR signal. Results on isofluorane (n = 5)- and halothane (n = 7)- anesthetized cats give a hyperglycemic t1/2 = 5.10 ± 0.11 min-1 (SE). Using Michaelis-Menten kinetics and an assumed half-saturation constant Kt = 5 ± 1 mM, we determined a maximal transport rate Tmax = 0.83 ± 0.19 µmol · g-1 · min-1, a cerebral metabolic rate of glucose CMRGlc = 0.22 ± 0.03 µmol · g-1 · min-1, and a normoglycemic cerebral influx rate CIRGlc = 0.37 ± 0.05 µmol · g-1 · min-1. Possible extension of this approach to positron emission tomography and proton NMR is discussed.

[13C]glucose utilization; brain; Michaelis-Menten kinetics; cat; nuclear magnetic resonance spectroscopy


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