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 [ t½= 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 t½= 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.