In vivo Glx and Glu measurements from GABA-edited MRS at 3 T

Abstract

In vivo quantification of glutamate (Glu) and γ-aminobutyric acid (GABA) using MRS is often achieved using two separate sequences: a short-echo point resolved spectroscopy (PRESS) acquisition for Glu and a Mescher-Garwood PRESS (MEGA-PRESS) acquisition for GABA. The purpose of this study was to examine the agreement of Glu and Glx (the combined signal of glutamate + glutamine) quantified from two different GABA-edited MEGA-PRESS acquisitions (GABA plus macromolecules, GABA+, T_E = 68 ms, and macromolecule suppressed, MMSup, T_E = 80 ms) with Glu and Glx quantified from a short-echo PRESS (PRESS-35, T_E = 35 ms) acquisition. Fifteen healthy male volunteers underwent a single scan session, in which data were acquired using the three acquisitions (GABA+, MMSup and PRESS-35) in both the sensorimotor and anterior cingulate cortices using a voxel size of 3 × 3 × 3 cm³ . Glx and Glu were quantified from the MEGA-PRESS data using both the OFF sub-spectra and the difference (DIFF) spectra. Agreement was assessed using correlation analyses, Bland-Altman plots and intraclass correlation coefficients. Glx quantified from the OFF sub-spectra from both the GABA+ and MMSup acquisitions showed poor agreement with PRESS-35 in both brain regions. In the sensorimotor cortex, Glu quantified from the OFF sub-spectra of GABA+ showed moderate agreement with PRESS-35 data, but this finding was not replicated in the anterior cingulate cortex. Glx and Glu quantified using the DIFF spectra of either MEGA-PRESS sequence were in poor agreement with the PRESS-35 data in both brain regions. In conclusion, Glx and Glu measured from MEGA-PRESS data generally showed poor agreement with Glx and Glu measured using PRESS-35.

Keywords: Glx; MEGA-; PRESS; PRESSGABA-edited MRS; glutamate.

Figure 1:

Voxel location and example spectra from a single volunteer in the sensorimotor cortex (A) and the anterior cingulate cortex (B). GABA and Glx resonances in the DIFF spectra have been scaled for visualisation.

Figure 2:

Scatter plots comparing Glx and Glu quantification methods in the sensorimotor cortex, with significant p-values in bold. (A) Glx and (B) Glu measurements from OFF-GABA+ and OFF-MMSup compared to the PRESS-35 measurements. (C) Glx and (D) Glu measured from the DIFF-GABA+ and DIFF-MMSup acquisitions compared to the PRESS-35 measurements. GABA+=GABA plus macromolecules (TE=68 ms), MMSup=macromolecule suppressed (TE=80 ms).

Figure 3:

Bland-Altman plots comparing Glx and Glu quantification methods in the sensorimotor cortex. (A) Glx quantified from OFF MEGA-PRESS compared with PRESS-35, (B) Glu quantified from OFF MEGA-PRESS compared with PRESS-35, (C) Glx quantified from DIFF MEGA-PRESS compared with PRESS-35, (D) Glu quantified from DIFF MEGA-PRESS compared with PRESS-35. The difference between the two paired measurements (PRESS-35 – MEGA-PRESS) is shown on the y-axis and the mean of the two measures is shown on the x-axis. Grey triangles show data from the GABA+ acquisition and black circles show data from the MMSup acquisition. Solid lines represent the overall mean difference and the dashed lines represent the limits of agreement based on the 95% confidence intervals.

Figure 4:

Intraclass correlation coefficient values and 95% confidence intervals comparing Glx and Glu quantified from OFF MEGA-PRESS data and PRESS-35 data for the sensorimotor cortex. Values of 0.5 (dashed line) indicate moderate agreement.

Figure 5:

Scatter plots comparing Glu and Glx quantification methods in the anterior cingulate cortex. (A) Glx and (B) Glu measurements from OFF-GABA+ and OFF-MMSup compared to the PRESS-35 measurements. (C) Glx and (D) Glu measured from the DIFF-GABA+ and DIFF-MMSup acquisitions compared to the PRESS-35 measurements.

Figure 6:

Bland-Altman plots comparing Glx and Glu quantification methods in the anterior cingulate cortex. (A) Glx quantified from OFF MEGA-PRESS compared with PRESS-35, (B) Glu quantified from OFF MEGA-PRESS compared with PRESS-35, (C) Glx quantified from DIFF MEGA-PRESS compared with PRESS-35, (D) Glu quantified from DIFF MEGA-PRESS compared with PRESS-35. The difference between the two paired measurements (PRESS-35 – MEGA-PRESS) is shown on the y-axis and the mean of the two measures is shown on the x-axis. Grey triangles show data from the GABA+ acquisition and black circles show data from the MM-Sup acquisition. Solid lines represent the overall mean difference and the dashed lines represent the limits of agreement based on the 95% confidence intervals.

Figure 7:

Intraclass correlation coefficient values and 95% confidence intervals comparing Glx and Glu quantified from OFF MEGA-PRESS data and PRESS-35 data for the sensorimotor cortex. Values of 0.5 (dashed line) indicate moderate agreement.