Echo-time optimization for J-difference editing of glutathione at 3T
Kimberly L Chan1,2,3, Nicolaas AJ Puts2,3, Karim Snoussi2,3, Ashley D Harris2,3,4,5,6, Peter B Barker2,3, and Richard AE Edden2,3

1Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, United States, 2Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, United States, 3F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 4Radiology, University of Calgary, Calgary, AB, Canada, 5Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada, 6CAIR Program, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada

Synopsis

Glutathione is involved in maintaining redox balance, and can be detected in vivo in brain tissue using MEGA-PRESS editing. In literature to-date, echo times from 68 to 131 ms have been stated as optimal; in this abstract, the TE-dependence of MEGA-edited GSH signals is investigated using simulations, and phantom and in vivo experiments. It is shown that, in vivo, there is a moderate (15%) benefit of detecting GSH at TE 120 ms over 68 ms. We also demonstrate that the longer echo time allows the use of higher-bandwidth, more rectangular slice-selective refocusing pulses, giving a further 57% gain in signal.

Purpose

Glutathione (GSH) abnormalities have been implicated in the pathophysiology of several neurological disorders (1-3). Since the GSH spectrum overlaps with stronger signals at 3T, spectral-editing is often used for its selective detection. However, it is difficult to estimate the optimal echo time (TE) for J-difference editing of GSH, due to strong coupling and T2-relaxation effects. Consequently, a large range of echo times, from 68 ms to 131 ms has been reported for in vivo GSH editing (3-6). The aim of this study was to investigate the TE-dependence of the edited GSH signal, taking into account the effects of scalar couplings and T2 relaxation, using density-matrix simulations, and phantom and in vivo experiments.

Methods

Spatially resolved MEGA-PRESS simulations were performed for TEs 70 ms-240 ms in 10 ms increments with parameters: simulated B0=3T; 20 ms sinc-Gaussian editing pulses (ON 4.56 ppm); GTST refocusing pulses (7,8); 2 kHz spectral width; 2048 points; 2.5-Hertz exponential line-broadening; zero-filling to 8192 datapoints. The first PRESS spin-echo duration (TE1) was fixed at 13.4 ms. Matched experiments were performed on a 50 mM GSH phantom using a Philips Achieva 3T scanner. Siv(TE), the in vivo signal intensity as a function of TE, can be estimated from phantom data:

Siv(TE) = Sp(TE) exp(-TE/T2,iv) exp(TE/T2,phantom)

where Sp(TE) is the signal in phantom experiments, T2-corrected for T2,phantom and T2,iv . Siv(TE) was calculated for estimated T2,iv values of 67 ms and 89 ms. The phantom T2 was assumed to be 260 ms (based on a similar GABA phantom at 3T (9)). Edited measurements in 5 healthy adults were performed at TEs of 120 ms, and the commonly used 68 ms in a (3.6 cm)3 parietal region using VAPOR water suppression. For shorter-TE (68 ms) measurements, “GTST” refocusing pulses were used (bandwidth=1300 Hz). For the longer TE, measurements were made either using GTST or longer-duration fmref07 refocusing pulses (bandwidth=2200 Hz; (7-10)). Other parameters matched the phantom experiments except TE1=26.6 ms in measurements using fmref07 pulses. Gannet (11,12) was used to frequency-and-phase-correct transients based on the NAA methyl peak, and the GSH-edited difference signal at ~2.95 ppm was integrated.

Results

Spatial dependence of the multiplet (red vs. green regions in Figure 2a), due to chemical shift displacement effects in the second refocusing pulse direction of the OFF spectra, result in difference spectra (DIFF) with no signal in the red regions. Figure 2b shows how the multiplet modulates with TE in the second refocusing pulse dimension. The OFF spectra modulate with TE (as intended) in green, but not red, regions. Figure 3a shows the simulated TE-modulation of the voxel-sum multiplet. Figure 3b shows the spectra integrals. The ON multiplets vary subtly (blue). The difference spectra have a peak intensity at TE 160-170 ms. Figure 4a,b show the TE-dependence of the spectra for the phantom, in good qualitative agreement with the simulations. Figure 4c shows the difference curve from Fig. 4b corrected to remove the phantom T2-weighting (T2=260 ms). Reintroducing estimated in vivo T2 relaxation, (67 ms, 89 ms) the maximum signal shifts to TE 120 ms from 160 ms. Figure 5 shows DIFF spectra from one subject (a) and average integral from five subjects (b). The signal at TE 120 ms with higher-bandwidth refocusing pulses is 57% larger than at TE=68 ms. The integral is 15% larger at TE=120 ms than at TE=68 ms when using lower bandwidth refocusing pulses.

Discussion

Good qualitative agreement in the TE-modulation was found between phantom experiments and simulations , suggesting that the simulation approach used, and the spin-system parameters, are accurate. Estimating in vivo T2 biases, these results predict that the optimal TE shifts to 120 ms; compared to the commonly used TE=68 ms, TE=120 ms will have 55% more signal if assuming in vivo T2=89 ms. In vivo data also show that TE=120 ms gives slightly more signal than 68 ms (15%), but less than phantom data suggested. One possible explanation is that the in vivo T2 is shorter than predicted. Another explanation arises from the different GSH lineshapes at the two TEs. At the shorter TE, the multiplet has negative outer lobes (Fig.3a, Fig.4a), which might lead to misidentification of the baseline in quantification, considering the signal as a positive signal within a baseline well. In vivo data show that the clearest benefit of the longer TE is the accommodation of better slice-selective RF pulses, which give more signal due to the higher bandwidth and more rectangular slice profile. Since these pulses typically also have a long duration, it is easier to implement them at longer TE values.

Acknowledgements

NIH grants P41 EB015909, R01 EB016089, and T32EB01002.

References

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Figures

Figure 1: Structure of glutathione (GSH) highlighting the chemical shifts and couplings of the cysteine moiety, on which edited detection is performed.

Figure 2: Simulations of the MEGA-PRESS edited multiplet. (a) Two-dimensional spatial simulations. (b) One-dimensional spatial simulations at TEs 70 ms - 240 ms.

Figure 3: Simulations of GSH as a function of TE, showing (a) the multiplet at ~2.95 ppm and (b) the integral curves.

Figure 4: Phantom experiments at a range of TEs, showing (a) the multiplet at ~2.95 ppm and (b) the integral curves. (c) Integral curves removing the effect of phantom T2 relaxation and simulating in vivo relaxation with T2=67 ms, 89 ms.

Figure 5: In vivo experiments, performed at TE = 68 ms, TE = 120 ms and TE = 120 ms with frequency-modulated refocusing pulses. (a) Spectra from one subject. (b) Average GSH integrals.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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