MEASUREMENT OF GLUTAMINE SYNTHESIS RATE IN THE HYPERAMMONAEMIC RAT BRAIN USING IN VIVO 1H AND 15N MRS

Glutamine synthetase is a critical step in the glutamate-glutamine cycle, the major mechanism of glutamate neurotransmission and is implicated in the mechanism of ammonia toxicity. 15N MRS is an alternative approach to 13C MRS in studying glutamate-glutamine metabolism. Moreover, the incorporation of 15N into [5-15N]Gln allows to measure glutamine synthetase activity (Vsyn) directly and can provide a more straightforward interpretation than 13C studies. Vsyn reflects a combination of the glutamate-glutamine cycle activity (Vnt) and net glutamine accumulation (Vsyn-Vnt). The net glutamine synthesis can be directly measured from 1H NMR. The aim of this study was to perform in vivo localized 1H MRS interleaved with 15N MRS to directly measure the net glutamine synthesis rate and the apparent glutamine synthesis rate under 15N labeled ammonia infusion in the rat brain, respectively. Methods: 1H and 15N MRS data were acquired interleaved on a 9.4T system (Varian/Magnex Scientific) using 8 rats. 15NH4Cl solution was infused continuously into the femoral vein for up to 10h (4.5mmol/h/kg) (1). 1H spectra were acquired and quantified as described previously (2). 15N unlocalized and localized spectra were acquired using the SIRENE sequence (3); and quantified using AMARES and an externa