Deuterated water imaging of the rat brain following metabolism of [2 H7 ]glucose

Magn Reson Med. 2021 Jun;85(6):3049-3059. doi: 10.1002/mrm.28700. Epub 2021 Feb 12.

Abstract

Purpose: To determine whether deuterated water (HDO) generated from the metabolism of [2 H7 ]glucose is a sensitive biomarker of cerebral glycolysis and oxidative flux.

Methods: A bolus of [2 H7 ]glucose was injected through the tail vein at 1.95 g/kg into Sprague-Dawley rats. A 2 H surface coil was placed on top of the head to record 2 H spectra of the brain every 1.3 minutes to measure glucose uptake and metabolism to HDO, lactate, and glutamate/glutamine. A two-point Dixon method based on a gradient-echo sequence was used to reconstruct deuterated glucose and water (HDO) images selectively.

Results: The background HDO signal could be detected and imaged before glucose injection. The 2 H NMR spectra showed arrival of [2 H7 ]glucose and its metabolism in a time-dependent manner. A ratio of the HDO to glutamate/glutamine resonances demonstrates a pseudo-steady state following injection, in which cerebral metabolism dominates wash-in of HDO generated by peripheral metabolism. Brain spectroscopy reveals that HDO generation is linear with lactate and glutamate/glutamine appearance in the appropriate pseudo-steady state window. Selective imaging of HDO and glucose is easily accomplished using a gradient-echo method.

Conclusion: Metabolic imaging of HDO, as a marker of glucose, lactate, and glutamate/glutamine metabolism, has been shown here for the first time. Cerebral glucose metabolism can be assessed efficiently using a standard gradient-echo sequence that provides superior in-plane resolution compared with CSI-based techniques.

Keywords: DMRI; HDO; [2H7]glucose; brain; metabolism.

Publication types

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

MeSH terms

  • Animals
  • Brain / diagnostic imaging
  • Carbon Isotopes
  • Glucose*
  • Glutamic Acid
  • Glutamine
  • Rats
  • Rats, Sprague-Dawley
  • Water*

Substances

  • Carbon Isotopes
  • Water
  • Glutamine
  • Glutamic Acid
  • Glucose