Glutamate measurements using edited MRS

Abstract

Purpose: To demonstrate J-difference coediting of glutamate using Hadamard encoding and reconstruction of Mescher-Garwood-edited spectroscopy (HERMES).

Methods: Density-matrix simulations of HERMES (TE 80 ms) and 1D J-resolved (TE 31-229 ms) of glutamate (Glu), glutamine (Gln), γ-aminobutyric acid (GABA), and glutathione (GSH) were performed. HERMES comprised four sub-experiments with editing pulses applied as follows: (A) 1.9/4.56 ppm simultaneously (ON_GABA /ON_GSH ); (B) 1.9 ppm only (ON_GABA /OFF_GSH ); (C) 4.56 ppm only (OFF_GABA /ON_GSH ); and (D) 7.5 ppm (OFF_GABA /OFF_GSH ). Phantom HERMES and 1D J-resolved experiments of Glu were performed. Finally, in vivo HERMES (20-ms editing pulses) and 1D J-resolved (TE 31-229 ms) experiments were performed on 137 participants using 3 T MRI scanners. LCModel was used for quantification.

Results: HERMES simulation and phantom experiments show a Glu-edited signal at 2.34 ppm in the Hadamard sum combination A+B+C+D with no overlapping Gln signal. The J-resolved simulations and phantom experiments show substantial TE modulation of the Glu and Gln signals across the TEs, whose average yields a well-resolved Glu signal closely matching the Glu-edited signal from the HERMES sum spectrum. In vivo quantification of Glu show that the two methods are highly correlated (p < 0.001) with a bias of ∼10%, along with similar between-subject coefficients of variation (HERMES/TE-averaged: ∼7.3%/∼6.9%). Other Hadamard combinations produce the expected GABA-edited (A+B-C-D) or GSH-edited (A-B+C-D) signal.

Conclusion: HERMES simulation and phantom experiments show the separation of Glu from Gln. In vivo HERMES experiments yield Glu (without Gln), GABA, and GSH in a single MRS scan.

Keywords: GABA; HERMES; J-difference; glutamate; glutathione.

Figure 1:

HERMES and the one-dimensional (1D) J-resolved simulations: a) Inversion profiles of editing pulses in the HERMES sub-experiments A-D editing Glu, GABA, and GSH; b) The Hadamard combinations of sub-experiments A-D result in the sum spectrum (A+B+C+D) with the Glu-edited signal without the Gln and GABA overlap, A+B−C−D spectrum with the GABA-edited signal, and A−B+C−D spectrum with the GSH-edited signal. c) The 1D J-resolved experiment shows the TE modulation of Glu, Gln, and GABA signals. The average of these signals yields the TE-averaged spectrum with the well-resolved and cleaner Glu signal without the Gln and GABA overlap. Phantom experiments in a Glu, Gln, and Cr phantom: d) The HERMES experiment at TE 80 ms shows refocusing of the Gln and Glu signals in experiments A and B and free evolution of these signals in experiments C and D; the sum spectrum (A+B+C+D) yields the Glu-edited signal without the Gln overlap; e) The 1D J-PRESS experiment shows the TE modulation of the Glu and Gln signals. The TE-averaged spectrum yields the Glu signal without the Gln overlap.

Figure 2:

a) Voxel localization in the frontal grey matter for the in vivo experiments using the HERMES and 1D J-resolved methods. b) HERMES spectra with the Glu-edited (A+B+C+D), GABA-edited (A+B−C−D), and GSH-edited (A−B+C−D) signals. c) TE-averaged spectrum with the resolved Glu signal at 2.34 ppm.

Figure 3:

Data Modeling without (left) and with (right) the default macromolecular and lipid basis functions in LCModel: a and b) HERMES sum and c and d) TE-averaged spectra.

Figure 4:

Correlations (a and b) and Bland-Altman analysis (c and d) of T2-corrected ratios estimated without (left) and with (right) the default macromolecular and lipid basis functions in LCModel. For Bland-Altman analyses (bottom), the difference (y-axis) is calculated (TE-averaged – Sum) relative to the means and expressed as a percentage; solid lines represent the mean of the difference; dotted lines represent the 95% confidence interval.