Unedited in vivo detection and quantification of γ-aminobutyric acid in the occipital cortex using short-TE MRS at 3 T.

TLDR: It is demonstrated that, under some experimental conditions, short‐TE MRS can be employed for the reproducible detection of GABA at 3 T, but that the technique should be used with caution, as the results are dependent on the experimental conditions.

Abstract: Short-TE MRS has been proposed recently as a method for the in vivo detection and quantification of gamma-aminobutyric acid (GABA) in the human brain at 3 T. In this study, we investigated the accuracy and reproducibility of short-TE MRS measurements of GABA at 3 T using both simulations and experiments. LCModel analysis was performed on a large number of simulated spectra with known metabolite input concentrations. Simulated spectra were generated using a range of spectral linewidths and signal-to-noise ratios to investigate the effect of varying experimental conditions, and analyses were performed using two different baseline models to investigate the effect of an inaccurate baseline model on GABA quantification. The results of these analyses indicated that, under experimental conditions corresponding to those typically observed in the occipital cortex, GABA concentration estimates are reproducible (mean reproducibility error, <20%), even when an incorrect baseline model is used. However, simulations indicate that the accuracy of GABA concentration estimates depends strongly on the experimental conditions (linewidth and signal-to-noise ratio). In addition to simulations, in vivo GABA measurements were performed using both spectral editing and short-TE MRS in the occipital cortex of 14 healthy volunteers. Short-TE MRS measurements of GABA exhibited a significant positive correlation with edited GABA measurements (R = 0.58, p < 0.05), suggesting that short-TE measurements of GABA correspond well with measurements made using spectral editing techniques. Finally, within-session reproducibility was assessed in the same 14 subjects using four consecutive short-TE GABA measurements in the occipital cortex. Across all subjects, the average coefficient of variation of these four GABA measurements was 8.7 +/- 4.9%. This study demonstrates that, under some experimental conditions, short-TE MRS can be employed for the reproducible detection of GABA at 3 T, but that the technique should be used with caution, as the results are dependent on the experimental conditions. Copyright (c) 2013 John Wiley & Sons, Ltd.

Figures

Table 1. List of simulated metabolites and average concentrations

Figure 6. Box plot diagram illustrating within-session reproducibility for all 14 subjects scanned. Box plot data were generated by breaking the short-TE spin-echo full-intensity acquired localised (SPECIAL) acquisition into four separate and consecutive blocks, and analysing each separately. Also shown are the g-aminobutyric acid (GABA) estimates from the full SPECIAL acquisition (dots). Cr, creatine.

Table 2. Details of simulated lipid (Lip) and macromolecule (MM) basis spectra

Figure 1. Contour plots showing mean estimation error (%EE) (a), reproducibility error (%ER) (b), average Cramer–Rao lower bound (CRLB) (c) and absolute reproducibility error (%ER2) (d) of g-aminobutyric acid (GABA) for simulated data as a function of linewidth (LW) and signal-to-noise ratio (SNR). LCModel analysis was performed with no baseline component by setting ‘NOBASE= T’.

Figure 2. Contour plots showing mean estimation error (%EE) (a), reproducibility error (%ER) (b), average Cramer–Rao lower bound (CRLB) (c) and absolute reproducibility error (%ER2) (d) of g-aminobutyric acid (GABA) for simulated data as a function of the linewidth (LW) and signal-to-noise ratio (SNR). LCModel analysis was performed using the default baseline model.

Frequently asked questions

Q1. What are the contributions mentioned in the paper "Unedited in vivo detection and quantification of aminobutyric acid in the occipital cortex using shortte mrs at 3t" ?

In this study, the authors investigated the accuracy and reproducibility of short-TE MRS measurements of GABA at 3 T using both simulations and experiments. Across all subjects, the average coefficient of variation of these four GABA measurements was 8. 7 4. 9 %. This study demonstrates that, under some experimental conditions, short-TE MRS can be employed for the reproducible detection of GABA at 3 T, but that the technique should be used with caution, as the results are dependent on the experimental conditions. Short-TE MRS measurements of GABA exhibited a significant positive correlation with edited GABA measurements ( R=0. 58, p < 0. 05 ), suggesting that short-TE measurements of GABA correspond well with measurements made using spectral editing techniques. 

Q2. What are the future works mentioned in the paper "Unedited in vivo detection and quantification of aminobutyric acid in the occipital cortex using shortte mrs at 3t" ?

Future studies are required to determine the efficacy of short-TE MRS for the detection of GABA in other brain regions, especially those associated with poor shim and lower SNR. 

Q3. How many averages were acquired using the MEGA-SPECIAL sequence?

Short-TE MR spectra were acquired using the SPECIAL sequence (4096 points; spectral width, 4000Hz; TR/TE = 3000/8.5ms; 192 averages) and edited GABA spectra were acquired using the MEGA-SPECIAL sequence (2048 points; spectral width, 2400Hz; TR/TE = 3000/68ms; 192 averages). 

Q4. What was the procedure for removing motion-corrupted scans?

Following the removal of motion-corrupted scans, but prior to signal averaging, a frequency and phase drift correction was performed. 

Q5. What was the baseline for the measurement of SNR in experimental data?

For the measurement of SNR in experimental data, the ‘signal’ was defined as the maximum intensity of the real part of the metabolite signal between 0.2 and 4.2 ppm, which always corresponded with the N-acetylaspartate (NAA) peak. 

Q6. What was the result of the averaging of the short-TE spectrum?

Following frequency and phase alignment of thescans, signal averaging was performed, resulting in a fully processed short-TE spectrum, and fully processed edit-on and edit-off MEGA-SPECIAL data. 

Q7. What is the striking side effect of using an incorrect baseline model?

The most striking side effect of using an incorrect baseline model is that the mean estimation error no longer decreases as SNR increases (Fig. 2a). 

Q8. What is the significance of the correlation between short-TE MRS measurements of GABA and edited?

Short-TE MRS measurements of GABA exhibited a significant positive correlation with edited GABA measurements (R=0.58, p<0.05), suggesting that short-TE measurements of GABA correspond well with measurements made using spectral editing techniques. 

Q9. What is the average coefficient of variation of short-TE GABA measurements?

from the in vivo study of within-session reproducibility, the average coefficient of variation of short-TE GABA measurements was calculated to be 8.7 4.9%, which agrees well with simulation, and compares favourably with previously published reproducibility values for edited measurements of GABA at the same field strength (14,15). 

Q10. How does the GABA reproducibility error in the LCModel model differ from the baseline?

provided that SNR is greater than or equal to 150, and LW is less than or equal to 9 Hz (criteria that can be satisfied by many experimental MRS data), the GABA reproducibility error (%ER2) remains below 20%, which suggests very good reproducibility despite the use of an incorrect baseline model. 

Q11. What was the default setting for the analysis of the simulated data?

All experimentally acquired short-TE SPECIAL MRS data were analysed in LCModel using the default baseline setting and the same basis set as used for the analysis of the simulated data as described above. 

Q12. What is the main reason why the results of this study may not be applicable?

In the case of pathology, when one or more metabolites may be outside of the normal range, the results of this study may not be applicable. 

Q13. What are the main factors that are not taken into account in a simulated spectra?

simulated spectra do not take into account certain experimental factors, such as subject motion (and other ghost signals), frequency drift and phase drift. 

Q14. What is the effect of the short-TE GABA measurements on the reproducibility of the measurements?

The results shown in Figure 5 demonstrate that, under the experimental conditions corresponding to those observed in the in vivo experiments performed here (LW=6Hz; SNR= 650), simulations predict that, although the GABA concentration will be systematically underestimated by approximately 34%, the reproducibility of the measurements (%ER = 8.9%, %ER2 = 5.9%) is comparable with previously published reproducibility values for edited measurements of GABA at the same field strength (14,15).