Simultaneous edited MR spectroscopy of glutathione and macromolecule-suppressed GABA
Georg Oeltzschner1,2, Kimberly L. Chan1,2,3, Muhammad G. Saleh1,2, Mark Mikkelsen1,2, Nicolaas A. J. Puts1,2, and Richard A. E. Edden1,2

1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 3Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States


γ-aminobutyric acid (GABA) and glutathione (GSH) can be simultaneously measured in the human brain in vivo at 3T using Hadamard encoding and reconstruction of MEGA-edited spectroscopy (HERMES). A drawback of conventional HERMES of GABA/GSH is the contamination of the edited GABA peak with co-edited macromolecular signals (MM), reducing the specificity of the method. We propose the addition of symmetrical suppression into the HERMES framework, and demonstrate the successful implementation of this approach in ten healthy subjects.


The main inhibitory neurotransmitter γ-aminobutyric acid (GABA) and the main antioxidant glutathione (GSH) are vital compounds for function and integrity of the human brain. Both metabolites can be detected in vivo at 3T using J-difference-edited MRS techniques such as MEGA-PRESS1,2. However, long acquisition times (~10 min per metabolite per voxel) limit the number of measurements that can be reasonably performed within a clinical MR exam. The finite selectivity of the editing pulses further causes macromolecular (MM) signals to be co-edited with GABA at 3 ppm, potentially amounting to as much as 50% of the observed GABA+MM (‘GABA+’) peak area. This lack of measurement specificity can be addressed by symmetrically arranging two editing pulses around the 1.7 ppm MM resonance3. Hadamard encoding and reconstruction of MEGA-edited spectroscopy (HERMES) is a multiplexed spectral editing scheme allowing simultaneous detection of GABA+ and GSH within a single experiment4. HERMES halves the total scan time relative to sequential measurements of GABA+ and GSH while maintaining the signal-to-noise ratio (SNR) for both edited compounds, but shares the issue of co-edited MM. We therefore introduce MM-suppressed HERMES for simultaneous editing of GSH and GABA without MM contamination.


MM-suppressed HERMES contains four sub-experiments (A, B, C and D), with different editing targets (Fig. 1a): (A) 1.9 ppm and 4.56 ppm (ONGABA, ONGSH); (B) 1.5 ppm and 4.56 ppm (OFFGABA, ONGSH); (C) 1.9 ppm (ONGABA, OFFGSH); (D) 1.5 ppm (OFFGABA, OFFGSH). Distinct Hadamard combinations of the sub-spectra give GSH- and MM-suppressed GABA-edited spectra, respectively: (GSH: A + B – C – D) and (GABA: A – B + C – D). To test the proposed scheme in vivo, ten healthy subjects (6 males, mean age 31.3 ± 8.3 y) were recruited with local IRB approval. MRS data were acquired from a 33 × 33 × 33 mm3 midline parietal voxel (Fig. 1b), using a 32-channel phased-array head coil on a Philips 3 T Achieva scanner. Common parameters for MRS scans were TR/TE = 2000/80 ms, 20-ms editing pulses (FWHM = 61.9 Hz), prospective frequency correction5 with 1 water-unsuppressed acquisition per 8 water-suppressed transients. Five MRS scans were acquired per subject: (1) MM-suppressed HERMES (320 averages); (2) conventional HERMES (320 averages); (3) conventional MEGA-PRESS of GABA (160 averages); (4) MM-suppressed MEGA-PRESS of GABA (160 averages); (5) MEGA-PRESS of GSH (160 averages). Data were processed using Gannet6, with frequency-and-phase correction (spectral egistration7 for GABA data, choline-based alignment for GSH data). The 3 ppm GABA resonance and the 2.95 ppm GSH resonances were fit with a single Gaussian model. Metabolite estimates were quantified with respect to the unsuppressed tissue water signal and reported in institutional units (i.u.).


MM-suppressed GABA-/GSH-edited HERMES spectra (orange), conventional GABA-/GSH-edited HERMES spectra (green), and MM-suppressed GABA-edited (blue) and GSH-edited MEGA-PRESS spectra (red) are overlaid for one subject in Fig. 2, with all of the above except the conventional HERMES spectra for all ten subjects displayed in Fig. 3, demonstrating good agreement between single-metabolite and dual-metabolite modalities. Mean GABA estimates were 1.10 ± 0.15 i.u. for MM-suppressed HERMES, and 1.13 ± 0.09 i.u. for MEGA-PRESS (mean difference: -0.03 ± 0.11 i.u.; paired t-test: P = 0.42). The mean GABA/GABA+ ratio was 0.60 ± 0.06 for the HERMES experiments, and 0.67 ± 0.08 for the MEGA-PRESS experiments. Mean GSH estimates were 0.59 ± 0.12 i.u. for MM-suppressed HERMES, and 0.66 ± 0.09 i.u. for MEGA-PRESS (mean difference: -0.07 ± 0.11 i.u.; paired t-test: P = 0.07). A mean SNR improvement of MM-suppressed HERMES over MEGA-PRESS was seen: +1.45 ± 0.25 for GABA and +1.32 ± 0.24 for GSH, i.e., close to the √2 improvement expected from the doubled number of averages compared to the respective separate MEGA-PRESS experiments.


The qualitative and quantitative agreement between MM-suppressed HERMES and the respective MEGA-PRESS acquisitions indicate successful implementation of symmetrical MM-suppression into the HERMES framework, removing one of the major shortcomings of conventional HERMES of GABA+/GSH.


MM-suppressed HERMES allows simultaneous editing of GABA/GSH without macromolecular contamination.


This work was supported by NIH grants R01 EB016089 and P41 EB015909. NAJP receives salary support from NIH grant K99 MH107719


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Figure 1. a. The MM-suppressed HERMES experiment incorporates six editing lobes, encoded in a Hadamard fashion to edit GSH and GABA with MM suppression. The 4.56 ppm lobes target GSH; the 1.9 ppm lobes target GABA. The MM resonance at 1.7 ppm is equally affected by the editing pulses symmetrically arranged around it (at 1.9 and 1.5 ppm), hence, the MM contribution in the GABA-edited Hadamard recombination is subtracted out. b. In vivo voxel placement in the parietal lobe of the brain, aligned along the midline.

Figure 2. Exemplary MM-suppressed HERMES, conventional HERMES, and conventional MEGA-PRESS spectra from one subject. Left: MM-suppressed GABA-edited HERMES (orange), GABA+ conventional HERMES (green), and MM-suppressed GABA-edited MEGA-PRESS (blue) spectra. Right: GSH-edited MM-suppressed HERMES (orange), conventional HERMES (green), and MEGA-PRESS (red) spectra.

Figure 3. MM-suppressed HERMES and MEGA-PRESS spectra from all 10 healthy subjects. Left column: MM-suppressed GABA-edited HERMES (orange) and MEGA-PRESS (blue) spectra; right column: GSH-edited MM-suppressed HERMES (orange) and MEGA-PRESS (red) spectra.

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)