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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 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 V cyc  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.

Determination of the Glutamate—Glutamine Cycling Flux Using Two-Compartment Dynamic Metabolic Modeling is Sensitive to Astroglial Dilution