ERETIC-normalized JPRESS and MEGA-PRESS editing for reliable quantification of GABA, Glu, Gln and GSH at 3T

Introduction: Increasing evidence underscores the role of gamma-amino- butyric-acid (GABA), glutamate (Glu), glutamine (Gln), glutathion (GSH), N-acetyl-aspartate (NAA), creatine (Cre), choline-containing compounds (PCh/GPC) and myo-inositol (mI) in various neurological and psychiatric disorders. In order to reliably quantify these metabolites in the human brain at 3T it is proposed to combine advanced 1 H MRS methods such as 2D J-resolved PRESS (JPRESS) and MEGA-PRESS GABA-editing with the Electric-Reference-To-access-In-vivo-Concentration (ERETIC) standard for normalization of quantification results. This work represents regarding implementations and a cross-validation against conventional 1D PRESS and internal water referencing. Methods: Measurements were performed on a 3T whole body system (Philips) using a transmit/receive birdcage coil equipped with an ERETIC setup that enables optical transmission and inductive injection of an artificial NMR-like reference signal of freely adjustable amplitude, phase, frequency and line-shape during acquisition of 1 H spectra [1]. ERETIC was implemented to be compatible with MEGA-PRESS GABA editing [2], 2D JPRESS [3] and conventional 1D PRESS. PRESS (TE=23/80ms, 128averages), MEGA-PRESS GABA-editing (TE=68ms, 256averages) and JPRESS (TE=24-200ms, 8 averages per Δt1=2ms) spectra have been recorded from a voxel (25x18x20mm) in the occipital lobe in eight healthy volunteers (Fig 1). Inner volume saturation [2] and VAPOR water suppression [4] was applied. PRESS spectra were quantified using LCModel, MEGA-PRESS spectra using AMARES (JMRUI 3.0) and 2D JPRESS data using ProFit [5]. Results: Quantification results for the selected group of metabolites were derived from PRESS (both TE) and JPRESS, while MEGA-PRESS only enabled the quantification of GABA. The SD of the average normalized amplitudes of each metabolite expressed as ratio to ERETIC (0 ppm / Fig 2) and to internal water is presented in Table1. For all tested sequences the metabolite/ERETIC ratio shows to be more reproducible than the metabolite/internal water ratio. The quantification reproducibility for all metabolites is generally improved by using 2D JPRESS instead of 1D PRESS of either echo-time. For the detection of GABA the result of JPRESS is comparable to MEGA-PRESS when the ERETIC based normalization is taken into account. Discussion: The combination of ERETIC and 2D JPRESS shows to be the best method for simultaneous quantification of GABA, Glu, Gln and GSH along with the conventional singlets, while ERETIC combined with MEGA-PRESS GABA-editing proofs to be a faster and reliable method for studies that target mainly GABA