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

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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 mumol.g-1.min-1, a cerebral metabolic rate of glucose CMRGlc = 0.22 +/- 0.03 mumol.g-1.min-1, and a normoglycemic cerebral influx rate CIRGlc = 0.37 +/- 0.05 mumol.g-1.min-1. Possible extension of this approach to positron emission tomography and proton NMR is discussed.