Simultaneous edited MRS of GABA and glutathione

Abstract

Edited MRS allows the detection of low-concentration metabolites, whose signals are not resolved in the MR spectrum. Tailored acquisitions can be designed to detect, for example, the inhibitory neurotransmitter γ-aminobutyric acid (GABA), or the reduction-oxidation (redox) compound glutathione (GSH), and single-voxel edited experiments are generally acquired at a rate of one metabolite-per-experiment. We demonstrate that simultaneous detection of the overlapping signals of GABA and GSH is possible using Hadamard Encoding and Reconstruction of Mega-Edited Spectroscopy (HERMES). HERMES applies orthogonal editing encoding (following a Hadamard scheme), such that GSH- and GABA-edited difference spectra can be reconstructed from a single multiplexed experiment. At a TE of 80ms, 20-ms editing pulses are applied at 4.56ppm (on GSH),1.9ppm (on GABA), both offsets (using a dual-lobe cosine-modulated pulse) or neither. Hadamard combinations of the four sub-experiments yield GABA and GSH difference spectra. It is shown that HERMES gives excellent separation of the edited GABA and GSH signals in phantoms, and resulting edited lineshapes agree well with separate Mescher-Garwood Point-resolved Spectroscopy (MEGA-PRESS) acquisitions. In vivo, the quality and signal-to-noise ratio (SNR) of HERMES spectra are similar to those of sequentially acquired MEGA-PRESS spectra, with the benefit of saving half the acquisition time.

Keywords: Editing; GABA; Glutathione; HERMES; Hadamard; Simultaneous.

Figure 1

HERMES editing of GSH and GABA. a) Inversion profiles of editing pulses applied in the four sub-experiments A-D. HERMES acquires all combinations of (ON_GSH, OFF_GSH) and (ON_GABA, OFF_GABA). b) Hadamard transformation of the sub-experiments yields the separate GSH- and GABA-edited spectra. c) Dual-frequency inversion in Experiment A is achieved using a cosine-sinc-Gaussian editing pulse. Experiments B and C use a more conventional sinc-Gaussian pulse to invert at a single offset.

Figure 2

Simulations and phantom saturation series. Bloch simulations of the editing pulses in each sub-experiment are shown in red. The water signals resulting from a series of phantom water-saturation experiments (shown in black) demonstrate the effect of editing pulses pulses in each sub-experiment. A secondary x-axis is plotted in black, corresponding to the editing pulse reference frequency offset that was applied to record each signal. As required, editing pulses are applied at 4.56 ppm in Experiments A and C and at 1.9 ppm in Experiments A and B. Signals at 3 ppm are unaffected in all four experiments.

Figure 3

Simulated HERMES spectra. A range from 2.42 to 3.62 ppm is plotted in all cases. a) HERMES experiments A-D as simulated for GSH-cysteine (left) and GABA (right). Evolution of coupling is refocused in ON experiments and unaffected in OFF experiments, as required. b) Hadamard-reconstructed spectra show GSH-edited signal in one combination and GABA-edited signal in the other.

Figure 4

Phantom HERMES spectra. A range from 2.42 to 3.62 ppm is plotted in all cases. a) HERMES experiments A-D as performed on a GSH phantom (left) and GABA phantom (right). Evolution of coupling is refocused in ON experiments and unaffected in OFF experiments, as required. b) Hadamard-reconstructed spectra show GSH-edited signal in one combination and GABA-edited signal in the other. Crosstalk between subspectra (e.g. GABA signal in the GSH-edited combination) is very small. c) MEGA-PRESS spectra of each metabolite show the same edited lineshapes. d) HERMES spectra of a phantom containing both GSH and GABA demonstrate successful simultaneous editing.

Figure 5

In vivo HERMES of one subject. A) The separate subspectra A-D are plotted, showing reduced residual water signal in ON_GSH spectra and absent NAA signal in ON_GABA spectra. The saturation range of the editing pulses is shown on each spectrum as a grayscale overlay. B) The Hadamard spectra show a GSH-edited signal at 2.95 ppm in the A-B+C-D combination and a GABA-edited spectrum in the A+B-C-D combination.

Figure 6

In vivo HERMES and MEGA-PRESS spectra from all subjects. Simultaneously acquired HERMES spectra are shown in orange and sequentially acquired MEGA-PRESS spectra are overlaid in each case in blue.

Figure 7

In vivo HERMES-PRIAM. GSH- and GABA-edited spectra (below) were acquired for two (3 cm)³ voxels (above) in a single 11 minutes acquisition. The orange spectra originate from the orange voxel and the blue spectra from the blue voxel.