Kinetic Analysis of Dynamic Deuterium MR Spectra for Simultaneous Assessment of Cerebral Glucose Consumption Rate and TCA Cycle Flux

Simultaneous assessment of cerebral glucose consumption rate (CMR _glc ) and TCA cycling rate (V _TCA ) is crucial for understanding neuroenergetics under various physiopathological conditions; nevertheless, such measurement was not possible. Recently, we developed a novel in vivo Deuterium ( ² H) MR (DMR) approach for noninvasively assessing glucose metabolisms in rat brain at 16.4 T. Following a brief injection of deuterated glucose, the dynamic labeling on glucose, glutamate/glutamine (Glx), water and lactate in the brain tissue can be monitored via tracking their well-resolved ² H signals. To quantify metabolic rates, a new kinetic model incorporating glycolysis, TCA cycle and -ketoglutarate/Glx exchange was developed in this study. By least-square fitting of the model with the experimental data obtained from dynamic DMR measurement in rat brains, major metabolic fluxes such as CMR _glc and V _TCA can be determined concurrently. Two different metabolic conditions were examined; increased CMR _glc (0.46 vs. 0.28 mol/g/min) and V _TCA (0.96 vs. 0.6 mol/g/min) were found under morphine infusion as compare to the deeper anesthesia of 2% isoflurane, which are consistent with previous in vivo ¹³ C or ¹ H MRS studies. In summary, we demonstrate that the new DMR approach in combine with the kinetic model described in this work is capable of simultaneously determining CMR _glc and V _TCA with high sensitivity and reliability.

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