1H magnetic resonance spectroscopy of 2H-to-1H exchange quantifies the dynamics of cellular metabolism in vivo

A method that quantifies signal reductions in proton magnetic resonance spectroscopy resulting from the replacement of H-1 with H-2 after the administration of a deuterated substrate can be used to monitor the turnover of cellular metabolites in vivo. Quantitative mapping of the in vivo dynamics of cellular metabolism via non-invasive imaging contributes to our understanding of the initiation and progression of diseases associated with dysregulated metabolic processes. Current methods for imaging cellular metabolism are limited by low sensitivities, costs or the use of specialized hardware. Here, we introduce a method that captures the turnover of cellular metabolites by quantifying signal reductions in proton magnetic resonance spectroscopy (MRS) resulting from the replacement of H-1 with H-2. The method, which we termed quantitative exchanged-label turnover MRS, only requires deuterium-labelled glucose and standard magnetic resonance imaging scanners, and with a single acquisition provides steady-state information and metabolic rates for several metabolites. We used the method to monitor glutamate, glutamine, gamma-aminobutyric acid and lactate in the brains of unaffected and glioma-bearing rats following the administration of H-2(2)-labelled glucose and H-2(3)-labelled acetate. Quantitative exchanged-label turnover MRS should broaden the applications of routine H-1 MRS.