Detection of [1,6-13C2]-glucose metabolism in rat brain by in vivo 1H[13C]-NMR spectroscopy

Localized, water-suppressed H-1-[C-13]-NMR spectroscopy was used to detect C-13-label accumulation in cerebral metabolites following the intravenous infusion of [1,6-C-13(2)]-glucose (Glc). The H-1-[C-13]-NMR method, based on adiabatic RF pulses, 3D image-selected in vivo spectroscopy (ISIS) localization, and optimal shimming, yielded high-quality H-1-[13C]-NMR spectra with optimal NMR sensitivity. As a result, the C-13 labeling of [4-C-13]-glutamate (Glu) and [4-C-13]-glutamine (Gln) could be detected from relatively small volumes (100 muL) with a high temporal resolution. The formation of [n-C-13]-Glu, [n-C-13]-Gln (n = 2 or 3), [2-C-13]-aspartate (Asp), [3-C-13]-Asp, [3-C-13]-alanine (Ala), and [3-C-13]-lactate (Lac) was also observed to be reproducible. The C-13-label incorporation curves of [4-C-13]-Glu and [4-C-13]-Gln provided direct information on metabolic pathways. Using a two-compartment metabolic model, the tricarboxylic acid (TCA) cycle flux was determined as 0.52 +/- 6.04 mumol/min/g, while the glutamatergic neurotransmitter flux equaled 0.25 +/- 0.05 mumol/min/g, in good correspondence with previously determined values.