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

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 C-13-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'). C-13-labeled glucose was administered and the apparent diffusion coefficients of the glycolytic products, {H-1-C-13}-lactate and {H-1-C-13}-alanine, were determined in rat intracerebral 9L glioma. To obtain insights into {H-1-C-13}-lactate compartmentation (intra-versus extracellular), the pulse sequence used very large diffusion weighting (50 ms/mu m(2)). 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, H-1 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 ([C-13] lactate) originates from an intracellular compartment. (c) 2005 Elsevier Inc. All rights reserved.