Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized 13 C magnetic resonance

Sci Rep. 2017 Sep 15;7(1):11719. doi: 10.1038/s41598-017-12086-z.

Abstract

The mammalian brain relies primarily on glucose as a fuel to meet its high metabolic demand. Among the various techniques used to study cerebral metabolism, 13C magnetic resonance spectroscopy (MRS) allows following the fate of 13C-enriched substrates through metabolic pathways. We herein demonstrate that it is possible to measure cerebral glucose metabolism in vivo with sub-second time resolution using hyperpolarized 13C MRS. In particular, the dynamic 13C-labeling of pyruvate and lactate formed from 13C-glucose was observed in real time. An ad-hoc synthesis to produce [2,3,4,6,6-2H5, 3,4-13C2]-D-glucose was developed to improve the 13C signal-to-noise ratio as compared to experiments performed following [U-2H7, U-13C]-D-glucose injections. The main advantage of only labeling C3 and C4 positions is the absence of 13C-13C coupling in all downstream metabolic products after glucose is split into 3-carbon intermediates by aldolase. This unique method allows direct detection of glycolysis in vivo in the healthy brain in a noninvasive manner.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Carbon-13 Magnetic Resonance Spectroscopy / methods*
  • Glucose / metabolism*
  • Glycolysis
  • Lactic Acid / metabolism
  • Mice
  • Pyruvic Acid / metabolism

Substances

  • Lactic Acid
  • Pyruvic Acid
  • Glucose