Simplified (13)C metabolic modeling for simplified measurements of cerebral TCA cycle rate in vivo

Abstract

(13)C NMR spectroscopy is a unique tool to measure the cerebral tricarboxylic acid (TCA) cycle rate in vivo. The measurement relies on metabolic modeling of glutamate C3 and C4 enrichment time courses during a (13)C-glucose intravenous infusion. Usual metabolic models require the plasma glucose and (13)C-glucose time courses as input functions, as well as the knowledge of Michaelis-Menten kinetics parameters governing passage through the blood-brain barrier. It is shown in the present work that, when using an infusion protocol yielding a rapidly stable plasma glucose fractional enrichment, metabolic modeling can be simplified in such a manner that this additional information on input function and glucose transport is no longer required, significantly simplifying the measurement of cerebral TCA cycle rate in vivo.