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A Universal Edited MRS Sequence for 4 Vendors
Muhammad G Saleh1,2, Daniel Rimbault3, Mark Mikkelsen1,2, Georg Oeltzschner1,2, Anna M Wang1,2, Dengrong Jiang1, Ali Alhamud3,4, Jamie Near5, Michael Schär1, Ralph Noeske6, James B Murdoch7, Lars Ersland8,9,10, Alexander R Craven8,9, Gerard Eric Dwyer8,9, Eli Renate Gruner8,9, Li Pan11, Sinyeob Ahn12, and Richard A 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, 3Medical Imaging Research Unit, Division of Biomedical Engineering, University of Cape Town, Cape Town, South Africa, 4University of Tripoli, Tripoli, Libyan, 5Douglas Mental Health University Institute and Department of Psychiatry, McGill University, Montreal, QC, Canada, 6GE Healthcare, Berlin, Germany, 7Canon Medical Research USA, Cleveland, OH, United States, 8Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway, 9Norwegian Center for Mental Disorders Research, University of Bergen, Bergen, Norway, 10Department of Clinical Engineering, Haukeland University Hospital, Bergen, Norway, 11Siemens Healthineers, Baltimore, MD, United States, 12Siemens Healthineers, San Francisco, CA, United States

Synopsis

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.

Introduction

MEGA-PRESS1, the most widely used spectral editing technique for measuring GABA, glutathione (GSH) and Lactate (Lac), subtracts out overlapping signals and selectively reveals the underlying signal-of-interest. Figure 1 shows four vendor-specific MEGA-PRESS implementations for GABA editing at TE 68ms: our own implementation based on the Philips PRESS sequence; the Siemens-distributed Work-In-Progress (WIP) sequence; the GE-distributed WIP sequence; and the Canon WIP sequence. The differences in RF pulse shapes, durations and sequence timing can lead to differences in the shape and intensity of the final edited signals2,3. A recent large multi-site study involving diverse implementations of MEGA-PRESS across sites and vendors suggested that approximately 30% of the total variance in the GABA+ data was attributed to site- and vendor-level differences in the implementation of MEGA-PRESS4. Therefore, in this abstract, we report on an effort to develop a new universal editing implementation (including HERMES functionality5) for the major MR vendor platforms with standardized RF pulse shapes, durations, amplitudes and sequence timings.

Methods

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.

Results

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.

Discussion

Phantom experiments indicate that both GABA- and Lac-edited spectra acquired using the universal sequence show substantially better agreement between vendors compared to the vendor-native sequences. A major difference in the vendor sequences arises from the editing pulse timing behavior as TE changes. For both Siemens and Canon sequences, the editing pulses are not TE/2 apart for all TEs, resulting in imperfect refocusing of coupling evolution in edit-ON scans and a loss of editing efficiency. In vivo experiments show modest improvement in the CV of GABA+/Cr and substantial improvement in the CV of Lac/Cr. These improvements in within-subject CV show the importance of standardizing slice-selective and editing pulses, pulse duration and sequence timings.

Conclusion

Both phantom and in vivo experiments demonstrate successful implementation of the universal edited MRS sequence, permitting consistent measurements of several metabolites across a range of TEs.

Acknowledgements

This work was supported by NIH grants R01 EB023963, R01 EB016089, U54 HD079123 and P41 EB015909, the National Research Foundation of South Africa Thuthuka grant TTK 150612119380, and the National Science and Engineering Research Council RGPIN-2014-06072 (Canada).

References

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.

Figures

Figure 1: Pulse sequence diagrams indicating RF pulse shapes and sequence timings for the vendor-native Philips, Siemens, GE and Canon sequences, and the universal sequence at TE 68 ms. The dual-lobe editing pulse shown on the universal sequence is used in the HERMES experiment to simultaneously invert GABA and GSH resonances.

Figure 2: Phantom experiments. Spectra acquired on the Philips, Siemens, GE and Canon scanners. a) MEGA-PRESS experiment using the GABA phantom (TE 68 ms) and Lac phantom (TE 140 ms) from vendor-native sequences (left) and the universal sequence (right). b) Edited spectra from HERMES experiments (TE 80 ms) acquired using the universal sequence, performed in a GABA phantom (left) and a GSH phantom (right). Edited signals from GABA and GSH appear in different Hadamard combinations as intended, with negligible crosstalk. ICC: intra-class correlation coefficient.

Figure 3: In vivo experiments using the universal sequence. Spectra acquired on Philips and Siemens scanners are overlaid for each subject. a) MEGA-PRESS GABA (TE 68 ms) and Lac (TE 140 ms) spectra. b) GABA- and GSH-edited HERMES spectra (TE 80 ms).

Table 1: Metabolite/Cr ratios and average within-subject CVs.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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