Detection of intracellular lactate with localized diffusion { 1H-13C}-spectroscopy in rat glioma in vivo

Josef Pfeuffer, Joseph C. Lin, Lance DelaBarre, Kamil Ugurbil, Michael Garwood

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19 Scopus citations

Abstract

The aim of this study was to compare the diffusion characteristic of lactate and alanine in a brain tumor model to that of normal brain metabolites known to be mainly intracellular such as N-acetylaspartate or creatine. The diffusion of 13C-labeled metabolites was measured in vivo with localized NMR spectroscopy at 9.4 T (400 MHz) using a previously described localization and editing pulse sequence known as ACED-STEAM ('adiabatic carbon editing and decoupling'). 13C-labeled glucose was administered and the apparent diffusion coefficients of the glycolytic products, { 1H-13C}-lactate and {1H- 13C}-alanine, were determined in rat intracerebral 9L glioma. To obtain insights into {1H-13C}-lactate compartmentation (intra- versus extracellular), the pulse sequence used very large diffusion weighting (50 ms/μm2). Multi-exponential diffusion attenuation of the lactate metabolite signals was observed. The persistence of a lactate signal at very large diffusion weighting provided direct experimental evidence of significant intracellular lactate concentration. To investigate the spatial distribution of lactate and other metabolites, 1H spectroscopic images were also acquired. Lactate and choline-containing compounds were consistently elevated in tumor tissue, but not in necrotic regions and surrounding normal-appearing brain. Overall, these findings suggest that lactate is mainly associated with tumor tissue and that within the time-frame of these experiments at least some of the glycolytic product ([13C] lactate) originates from an intracellular compartment.

Original languageEnglish (US)
Pages (from-to)129-138
Number of pages10
JournalJournal of Magnetic Resonance
Volume177
Issue number1
DOIs
StatePublished - Nov 2005

Bibliographical note

Funding Information:
The authors thank Dr. Hellmut Merkle for expert technical assistance on the magnet systems. This work was supported by National Institutes of Health grants RR08079, CA64338, and the W.M. Keck Foundation.

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

Keywords

  • Cerebral metabolites
  • Diffusion-weighted {H-C} NMR spectroscopy
  • Distribution space
  • Glioma
  • Intracellular lactate
  • Rat brain in vivo

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