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-C-13]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 B-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(1/2) = 1n2/(k(2) + k(3))] from the time dependence of the NMR signal. Results on isofluorane (n = 5)- and halothane (n = 7)- anesthetized cats give a hyperglycemic t(1/2) = 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 mu mol.g(-1).min(-1), a cerebral metabolic rate of glucose CMRGlc = 0.22 +/- 0.03 mu mol.g(-1).min(-1), and a normoglycemic cerebral influx rate CIRGlc = 0.37 +/- 0.05 mu mol.g(-1).min(-1). Possible extension of this approach to positron emission tomography and proton NMR is discussed.