In vivo detection of brain Krebs cycle intermediate by hyperpolarized magnetic resonance

J Cereb Blood Flow Metab. 2012 Dec;32(12):2108-13. doi: 10.1038/jcbfm.2012.136. Epub 2012 Sep 19.


The Krebs (or tricarboxylic acid (TCA)) cycle has a central role in the regulation of brain energy regulation and metabolism, yet brain TCA cycle intermediates have never been directly detected in vivo. This study reports the first direct in vivo observation of a TCA cycle intermediate in intact brain, namely, 2-oxoglutarate, a key biomolecule connecting metabolism to neuronal activity. Our observation reveals important information about in vivo biochemical processes hitherto considered undetectable. In particular, it provides direct evidence that transport across the inner mitochondria membrane is rate limiting in the brain. The hyperpolarized magnetic resonance protocol designed for this study opens the way to direct and real-time studies of TCA cycle kinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport, Active
  • Brain Chemistry / physiology
  • Brain* / diagnostic imaging
  • Brain* / metabolism
  • Citric Acid Cycle / physiology*
  • Ketoglutaric Acids / metabolism*
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mitochondria / diagnostic imaging
  • Mitochondria / metabolism
  • Mitochondrial Membranes / diagnostic imaging
  • Mitochondrial Membranes / metabolism*
  • Neurons* / diagnostic imaging
  • Neurons* / metabolism
  • Radiography
  • Rats
  • Rats, Sprague-Dawley


  • Ketoglutaric Acids