The anterior cingulate cortex GABA levels with varied tissue composition measured by in vivo single voxel MRS
Meining Chen1, Gaiying Li1, Zhuwei Zhang1, Luguang Chen1, Mengchao Pei1, Xu Yan2, and Jianqi Li1

1Shanghai Key Laboratory of Magnetic Resonance and Department of Physics, East China Normal University, Shanghai, China, People's Republic of, 2MR Collaboration NE Asia, Siemens Healthcare, Shanghai, China, People's Republic of

Synopsis

Owing to relatively low concentration of GABA in the brain, a large voxel size is normally applied in MRS to achieve a high signal-to-noise ratio, but with combined signal from white matter, gray matter and cerebrospinal fluid. The tissue contribution in GABA measurement remains to be resolved. GABA levels from three closely adjacent voxels with varied tissue composition in the anterior cingulate cortex were acquired by using MEGA-PRESS. GABA level was found to be significantly higher in gray matter than in white matter.

Purpose

The goal of this study is to investigate the correlation between GABA level and varied tissue composition from the closely adjacent voxels with different fraction of gray matter (GM) and white matter (WM) in the anterior cingulate cortex (ACC).

Materials and Methods

Ten right-handed male healthy volunteers took part in this study. All measurements were carried out on a clinical 3T whole-body MR scanner(MAGNETOM Trio, Siemens Healthcare, Erlangen, Germany) using a 32-channel, phased array, receive-only head coil for signal detection. A three-dimensional high-resolution T1-weighted image was acquired using MP-RAGE sequence. Then single voxel edited 1H-MR spectra from three adjacent voxels in each subject were acquired using MEGA-PRESS sequence. The first voxel with a size of 25×25×40 mm3 was placed in the middle of ACC and then was shifted to right by 10mm and 20mm respectively to get the second and the third voxels (Fig 1). Metabolite fitting and quantitation of the MEGA-PRESS difference spectra was performed by two researchers using jMRUI software package version 5.2, their measured value of GABA+ (GABA + Macromolecule) and NAA were then averaged (Fig 2). To determine the fraction of tissue composition in the voxels, high-resolution T1-weighted image were segmented into GM, WM and CSF by using SPM8. The percentages of WM (fGM) and GM (fWM) in the voxels were calculated using an in-house developed program. The GABA peak fit area in each voxel was referenced to the corresponding normalized NAA with ignoring tissue composition variation on NAA to obtain the GABA/NAA’ ratio1. A linear regression analysis was performed to investigate the relation between and fraction of gray matter in the voxels; the values of level in the pure gray matter and white matter were estimated by extrapolating the regression line to =1 and =0, respectively.

Result

When the voxel was shifted from the center to the right, fraction of gray matter (fGM) decreased gradually. The mean in the ACC were 0.65 ± 0.03, 0.51 ± 0.03, 0.39 ± 0.03 for the three adjacent voxels, respectively. GABA level depended significantly on fraction of gray matter (r=0.479, p=0.007) (Fig 3). The regression analysis suggested GABA+ signal ratio of pure gray matter to pure white matter was 1.74.

Discussion and conclusion

GABA signal ratio of pure gray matter to pure white matter was 1.74, which was close to the findings of previous studies2-5 that measured the GABA using J-difference editing method and GABA was contaminated with macromolecule contribution. Our result is much lower than the values reported by Choi IY6, Bhattacharyya PK7 and Ganji SK8, which may be due to different methods for GABA measurement and removal of macromolecule contamination in these studies. In summary, GABA level referenced to normalized NAA was significantly higher in gray matter than in white matter. Our results highlight the importance of careful control on tissue composition when investigating GABA level since the difference caused by tissue composition may dominate. It’s essential to correct gray and white matter differences in the interpretation of neurological and psychiatric disorders about GABA in clinic.

Acknowledgements

This study was supported in part by grants from The National Natural Science Foundation of China (81271533).

References

1. Durst CR, Michael N, Tustison NJ, et al. Noninvasive evaluation of the regional variations of GABA using magnetic resonance spectroscopy at 3 Tesla. Magn Reson Imaging. 2015; 33(5): p. 611-7.

2. Jensen JE, Frederick Bde B, Renshaw PF. Grey and white matter GABA level differences in the human brain using two-dimensional, J-resolved spectroscopic imaging. NMR Biomed. 2005; 18(8): p. 570-6.

3. Harris AD, Puts NA, Eddenet RA. Tissue correction for GABA-edited MRS: Considerations of voxel composition, tissue segmentation, and tissue relaxations. J Magn Reson Imaging. 2015.

4. Choi C, Bhardwaj PP, Kalra S, et al. Measurement of GABA and contaminants in gray and white matter in human brain in vivo. Magn Reson Med. 2007; 58(1): p. 27-33.

5. Geramita M, van der Veen JW, Barnett AS, et al. Reproducibility of prefrontal gamma-aminobutyric acid measurements with J-edited spectroscopy. NMR Biomed. 2011; 24(9): p. 1089-98.

6. Choi IY, Lee SP, Merkle H, et al. In vivo detection of gray and white matter differences in GABA concentration in the human brain. Neuroimage. 2006; 33(1): p. 85-93.

7. Bhattacharyya PK, Phillips MD, Stone LA, et al. In vivo magnetic resonance spectroscopy measurement of gray-matter and white-matter gamma-aminobutyric acid concentration in sensorimotor cortex using a motion-controlled MEGA point-resolved spectroscopy sequence. Magn Reson Imaging. 2011; 29(3): p. 374-9.

8. Ganji SK, An Z, Banerjee A, et al. Measurement of regional variation of GABA in the human brain by optimized point-resolved spectroscopy at 7 T in vivo. NMR Biomed. 2014; 27(10): p. 1167-75.

Figures

Fig 1. The locations of three adjacent voxels which cover mostly the gray matter(red),the white matter (green), and the mixed voxel (blue) in the anterior cingulate cortex. Sagittal and traverse views are presented from left to right.

Fig.2 AMARES-fit of metabolites in edited spectrum showing GABA pseudo-doublet at 3.02ppm and inverted NAA at 2.02 ppm in violet. Residual water signal have been removed by HSVD filter. Exponential filtering with 4Hz was applied.

Fig.3 Pearson’s correlations of GABA/NAA’ level versus fraction of gray matter (fGM) in the anterior cingulate cortex. Data were acquired from three adjacent voxels in the ACC of ten subjects with 30 voxels, respectively. Data of individual subjects are labeled by various shapes.



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