Oxidation of [U- 13 C]glucose in the human brain at 7T under steady state conditions

Magn Reson Med. 2017 Dec;78(6):2065-2071. doi: 10.1002/mrm.26603. Epub 2017 Jan 23.

Abstract

Purpose: Disorders of brain energy metabolism and neurotransmitter recycling have been implicated in multiple neurological conditions. 13 C magnetic resonance spectroscopy (13 C MRS) during intravenous administration of 13 C-labeled compounds has been used to measure turnover rates of brain metabolites. This approach, however, requires prolonged infusion inside the magnet. Proton decoupling is typically required but may be difficult to implement with standard equipment. We examined an alternative approach to monitor glucose metabolism in the human brain.

Methods: 13 C-enriched glucose was infused in healthy subjects outside the magnet to a steady-state level of 13 C enrichment. Subsequently, the subjects were scanned at 7T for 60 min without 1 H decoupling. Metabolic modeling was used to calculate anaplerosis.

Results: Biomarkers of energy metabolism and anaplerosis were detected. The glutamate C5 doublet provided information about glucose-derived acetyl-coenzyme A flux into the tricarboxylic acid (TCA) cycle via pyruvate dehydrogenase, and the bicarbonate signal reflected overall TCA cycle activity. The glutamate C1/C5 ratio is sensitive to anaplerosis.

Conclusion: Brain 13 C MRS at 7T provides information about glucose oxidation and anaplerosis without the need of prolonged 13 C infusions inside the scanner and without technical challenges of 1 H decoupling, making it a feasible approach for clinical research. Magn Reson Med 78:2065-2071, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Keywords: 13C MRS; 13C bicarbonate; 7 Tesla; TCA cycle; brain energy metabolism.

MeSH terms

  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Carbon Isotopes / chemistry*
  • Citric Acid Cycle
  • Feasibility Studies
  • Glucose / chemistry*
  • Humans
  • Image Processing, Computer-Assisted
  • Ketone Oxidoreductases / metabolism
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Magnetics
  • Male
  • Neurotransmitter Agents
  • Oxygen / chemistry*
  • Protons

Substances

  • Carbon Isotopes
  • Neurotransmitter Agents
  • Protons
  • Ketone Oxidoreductases
  • pyruvate dehydrogenase (NADP+)
  • Glucose
  • Oxygen