Determination of the glutamate-glutamine cycling flux using two-compartment dynamic metabolic modeling is sensitive to astroglial dilution

Over the last decade (13)C magnetic resonance spectroscopy ((13)C MRS) combined with the infusion of [1-(13)C] glucose has been used to measure the cerebral rate of the glutamate-glutamine cycle (V(cyc)). However, the effect of the astroglial label dilution pathways on the accuracy and precision of the (13)C MRS measurement of V(cyc) has not been evaluated or realized. In this report, we use the numerical Monte Carlo method to study the effect of astroglial dilution on the reliability of extracting Vcyc using the neuronal-astroglial two-compartment metabolic model and [1-(13)C] glucose infusion. The results show that omission of the astroglial dilution flux leads to a large loss in the sensitivity of the glutamine turnover curve to V(cyc). When the measured isotopic dilution of cerebral glutamine is accounted for in the analysis, the value of V(cyc) can be precisely and accurately determined.