MEGA-PRESS is the most widely used pulse sequence for edited MRS of low-concentration metabolites, e.g. GABA, glutathione and lactate. However, current implementations of MEGA-PRESS are diverse across MR vendors, leading to differences in the shape and intensity of the final edited signal. We demonstrate a new universal editing sequence (with MEGA and HERMES functionality) for the major MR vendor platforms with standardized RF pulse shapes, durations, amplitudes and sequence timings. Phantom and in vivo experiments show excellent agreement among vendors, including consistency in lineshape and reduced variation in concentration measurements.
Experiments were conducted on Philips Achieva, Siemens MAGNETOM Prisma, GE Discovery MR750 and Canon Vantage 3 T MRI scanners using 32-channel head coils.
Phantom Experiments: Phantoms containing 10 mM GABA, 20 mM GSH, 5 mM Lac or 7.5 mM Lac were prepared. MEGA-PRESS for GABA (or Lac) editing was conducted by applying the editing pulses at 1.9 (or 4.1) ppm in ONGABA (ONLac) steps. Additional scan parameters were as follows: TR 2000 ms; TE 68 ms for GABA (or 140 ms for Lac); 2048 datapoints; spectral width 2 kHz; voxel size 27 ml; and 64 transients. HERMES consists of four Hadamard-encoded sub-experiments (A, B, C, D), the Hadamard combinations of which yield simultaneously acquired GABA- (A+B-C-D) and GSH-edited (A-B+C-D) spectra. Acquisition parameters mimicked the GABA acquisition, except TE 80ms. Line broadening of ~3 Hz was applied to all phantom data. The intraclass correlation coefficient (ICC)6 was calculated to assess spectral similarity among vendor-native spectra and among universal-sequence spectra acquired on each platform.
In Vivo Experiments: Six adult volunteers were scanned on Philips and Siemens scanners. In each subject, MEGA-PRESS was performed for GABA and Lac, using the vendor-native and universal sequences. Additionally, HERMES for GABA and GSH was performed using the universal sequence. Data were acquired from a voxel positioned in mid-cingulate cortex with the same acquisition parameters as the phantom experiments, except 224 transients were acquired. The voxel size was 3x3x3 cm3 for all experiments, except for Lac MEGA-PRESS, which had a voxel size of 3x3x5 cm3.
Data Processing: In vivo data were analyzed using Gannet7. GABA+/Cr, Lac/Cr and GSH/Cr integral ratios were calculated. Within-subject coefficients of variance (CVs) were calculated between the Philips and Siemens data for the vendor-native sequences and for the universal sequence.
Phantom Experiments: GABA-edited and Lac-edited MEGA-PRESS spectra (Figure 2a) show a better agreement between the universal spectra (ICC 0.96/0.98 GABA/Lac) than the vendor-native spectra (ICC 0.91/0.74 GABA/Lac). GABA and GSH HERMES yields both GABA- and GSH-edited spectra with negligible levels of crosstalk (Figure 2b), and strong agreement among vendors for GABA and GSH (ICC 0.97/0.99).
In Vivo Experiments: The universal sequence resulted in edited signals at 3 ppm for GABA, at 1.3 ppm for Lac, and at 2.95 ppm for GSH in the respective spectra (Figure 3). Table 1 shows the quantitative measurements of metabolite ratios and average within-subject variability. Briefly, GABA+/Cr and Lac/Cr CVs from the vendor-native sequences were larger than those from the universal sequence. The GABA+/Cr from the universal HERMES sequence showed similar CVs to the universal MEGA-PRESS.
1. Mescher M, Merkle H, Kirsch J, Garwood M, Gruetter R. Simultaneous in vivo spectral editing and water suppression. NMR Biomed 1998;11:266-272.
2. Mullins PG, McGonigle DJ, O'Gorman RL, Puts NA, Vidyasagar R, Evans CJ, Cardiff Symposium on MRSoG, Edden RA. Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA. Neuroimage 2014;86:43-52.
3. Edden RA, Barker PB. Spatial effects in the detection of γ‐aminobutyric acid: Improved sensitivity at high fields using inner volume saturation. Magn Reson Med 2007;58:1276-1282.
4. Mikkelsen. M, Barker. PB, Bhattacharyya. PK, Brix. MK, Buur. PF, Cecil. KM, Chan. KL, Chen David. Y-T, Craven. AR, Cuypers. K, Dacko. M, Duncan. NW, Dydak. U, Edmondson. DA, Ende. G, Ersland. L, Gao. F, Greenhouse. I, Harris. AD, He. N, Heba. S, Hoggard. N, Hsu. T-W, Jansen. JFA, Kangarlu. A, Lange. T, Lebel. RM, Li. Y, Lin. C-YE, Liouz. J-K, Lirng. JF, Liu. F, Ma. R, Maes. C, Moreno-Ortega. M, Murray. SO, Noah. S, Noeske. R, Noseworthy. MD, Oeltzschner. G, Prisciandaro. JJ, Puts. NAJ, Roberts. TPL, Sack. M, Sailasuta. N, Saleh. MG, Schallmo. M-P, Simard. N, Swinnen. SP, Tegenthoff. M, Truong. P, Wang. G, Wilkinson. ID, Wittsack. H-J, Xu. H, Yan. F, Zhang. C, Zipunnikov. V, Zöllner. HJ, Edden RAE. Big GABA: Edited MR spectroscopy at 24 research sites. Neuroimage 2017;159:32.
5. Saleh MG, Oeltzschner G, Chan KL, Puts NA, Mikkelsen M, Schär M, Harris AD, Edden RA. Simultaneous edited MRS of GABA and glutathione. Neuroimage 2016;15:576-582.
6. McGraw KO, Wong SP. Forming inferences about some intraclass correlation coefficients. Psychological methods 1996;1:30-46.
7. Edden RA, Puts NA, Harris AD, Barker PB, Evans CJ. Gannet: A batch‐processing tool for the quantitative analysis of gamma‐aminobutyric acid–edited MR spectroscopy spectra. J Magn Reson Imaging 2014;40:1445-1452.