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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 (lsquo;adiabatic carbon editing and decouplinglsquo;). 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). Multiexponential 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.