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

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 [t( 1/4 ) = 1n2/(k₂ + k₃)] from the time dependence of the NMR signal. Results on isofluorane (n = 5)- and halothane (n = 7)-anesthetized cats give a hyperglycemic t( 1/4 ) = 5.10 ± 0.11 min^-1 (SE). Using Michaelis-Menten kinetics and an assumed half- saturation constant K(t) = 5 ± 1 mM, we determined a maximal transport rate T(max) = 0.83 ± 0.19 μmol · g^-1 · min^-1, a cerebral metabolic rate of glucose CMR(Glc) = 0.22 ± 0.03 μmol · g^-1 · min^-1, and a normoglycemic cerebral influx rate CIR(Glc) = 0.37 ± 0.05 μmol · g^-1 · min^-1. Possible extension of this approach to positron emission tomography and proton NMR is discussed.