Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Apr 15;6:24564.
doi: 10.1038/srep24564.

Effects of Frequency Drift on the Quantification of Gamma-Aminobutyric Acid Using MEGA-PRESS

Free PMC article

Effects of Frequency Drift on the Quantification of Gamma-Aminobutyric Acid Using MEGA-PRESS

Shang-Yueh Tsai et al. Sci Rep. .
Free PMC article


The MEGA-PRESS method is the most common method used to measure γ-aminobutyric acid (GABA) in the brain at 3T. It has been shown that the underestimation of the GABA signal due to B0 drift up to 1.22 Hz/min can be reduced by post-frequency alignment. In this study, we show that the underestimation of GABA can still occur even with post frequency alignment when the B0 drift is up to 3.93 Hz/min. The underestimation can be reduced by applying a frequency shift threshold. A total of 23 subjects were scanned twice to assess the short-term reproducibility, and 14 of them were scanned again after 2-8 weeks to evaluate the long-term reproducibility. A linear regression analysis of the quantified GABA versus the frequency shift showed a negative correlation (P < 0.01). Underestimation of the GABA signal was found. When a frequency shift threshold of 0.125 ppm (15.5 Hz or 1.79 Hz/min) was applied, the linear regression showed no statistically significant difference (P > 0.05). Therefore, a frequency shift threshold at 0.125 ppm (15.5 Hz) can be used to reduce underestimation during GABA quantification. For data with a B0 drift up to 3.93 Hz/min, the coefficients of variance of short-term and long-term reproducibility for the GABA quantification were less than 10% when the frequency threshold was applied.


Figure 1
Figure 1. The range of the frequency shifts across the MRS scans for 60 datasets from 23 subjects.
The largest frequency shift in this study was 34.1Hz, which is 3.93 Hz/min.
Figure 2
Figure 2. (Top) The 128 edit-off spectra from one subject.
(Bottom) Aligned edit-off spectra obtained using post-processing procedures based on the Cr peak.
Figure 3
Figure 3. Averaged edit-on, edit-off and edited spectra (the difference between the edit-on and edit-off data) from the same subject shown in Fig. 3.
The inverted NAA peak, Glx peaks and GABA peak can be found at 2.02 ppm, 3.75 ppm and 3.0 ppm, respectively, on the edited spectrum.
Figure 4
Figure 4
The scatter plot and linear regression of (a) GABA+/H2O and (b) Glx/H2O versus the frequency shift. For selected datasets, GABA+/H2O and Glx/H2O were quantified using the frequency shift threshold at 0.125 ppm (black squares). The slope was −0.0047 for GABA+/H2O and 0.0064 for Glx/H2O (black line). For full datasets, GABA+/H2O and Glx/H2O were quantified without a frequency shift threshold (red circles). The slope was −0.0101 for GABA+/H2O and 0.0175 for Glx/H2O (red line).
Figure 5
Figure 5
The results of the linear regression analysis (slope and R2) using a frequency shift threshold from 0.075 ppm to 0.275 ppm (a,c) for GABA+/H2O and (b,d) for Glx/H2O. (e) The numbers of averages and (f) normalized SNR at the nine frequency thresholds. For GABA+/H2O, the regression line showed a statistically significant correlation, with P < 0.01 for the frequency shift threshold at 0.175 ppm to 0.275 and with P < 0.05 for the frequency shift threshold at 0.15 ppm. For Glx/H2O, the regression line showed a statistically significant correlation with P < 0.01 for the frequency shift threshold at 0.1 ppm to 0.275 ppm and with P < 0.05 for a frequency shift threshold at 0.075 ppm.

Similar articles

See all similar articles

Cited by 5 articles


    1. Muthukumaraswamy S. D., Evans C. J., Edden R. A., Wise R. G. & Singh K. D. Individual variability in the shape and amplitude of the BOLD-HRF correlates with endogenous GABAergic inhibition. Human brain mapping 33, 455–465, doi: 10.1002/hbm.21223 (2012). - DOI - PMC - PubMed
    1. Boy F. et al. Individual differences in subconscious motor control predicted by GABA concentration in SMA. Current biology: CB 20, 1779–1785, doi: 10.1016/j.cub.2010.09.003 (2010). - DOI - PMC - PubMed
    1. Muthukumaraswamy S. D., Edden R. A., Jones D. K., Swettenham J. B. & Singh K. D. Resting GABA concentration predicts peak gamma frequency and fMRI amplitude in response to visual stimulation in humans. Proc Natl Acad Sci USA 106, 8356–8361, doi: 10.1073/pnas.0900728106 (2009). - DOI - PMC - PubMed
    1. Edden R. A., Muthukumaraswamy S. D., Freeman T. C. & Singh K. D. Orientation discrimination performance is predicted by GABA concentration and gamma oscillation frequency in human primary visual cortex. The Journal of neuroscience: the official journal of the Society for Neuroscience 29, 15721–15726, doi: 10.1523/JNEUROSCI.4426-09.2009 (2009). - DOI - PMC - PubMed
    1. Jocham G., Hunt L. T., Near J. & Behrens T. E. A mechanism for value-guided choice based on the excitation-inhibition balance in prefrontal cortex. Nature neuroscience 15, 960–961, doi: 10.1038/nn.3140 (2012). - DOI - PMC - PubMed

Publication types