Spectral-editing measurements of GABA in the human brain with and without macromolecule suppression

Abstract

Purpose: The conventional spectral-editing experiment used to measure GABA in the human brain also contains a contribution from macromolecules (MM), and the combined GABA plus MM signal is often referred to as "GABA+". More recently, methods have been developed to estimate GABA free from MM contamination. In this study, the relationship between GABA acquired with MM suppression and conventional GABA+ measurements was examined.

Methods: GABA-edited MEGA-PRESS experiments with and without MM suppression were performed in the sensorimotor and occipital cortex of 12 healthy subjects at 3 Tesla. The correlation between GABA+ and MM-suppressed GABA measures was then determined.

Results: Across all data, a significant correlation between GABA+ and MM-suppressed GABA was found (r = 0.48; P = 0.02). Regionally, the sensorimotor voxel showed a trend toward a correlation of r = 0.53, P = 0.07 and the occipital voxel did not show a correlation, r = 0.058, P = 0.9.

Conclusion: GABA+ and MM-suppressed GABA are moderately correlated, but statistical power to reveal this relationship may vary regionally. The MM signal, while often assumed to be functionally irrelevant, appears to show inter-individual and inter-regional variance that impacts the correlation of GABA+ and MM-suppressed GABA.

Keywords: GABA; brain; edited MRS; macromolecules GABA+.

FIG. 1

Comparison of the conventional GABA+ acquisition with the MM-suppressed GABA acquisition. a: Schematic to illustrate the differences in the ON and OFF editing pulses in the GABA+ and MM-suppressed GABA experiments. b: Pulse sequences of the conventional GABA+ and the MM-suppressed GABA acquisitions. In the conventional GABA+ acquisition, the TE = 68 ms and the frequency selective editing pulses (shaded) are limited to 14 ms. By increasing the TE to 80 ms, the editing pulses can be 20 ms in duration, thus increasing their selectivity for the MM-suppressed acquisition. Pulse sequence diagrams in b are reproduced from Edden et al (17). c: Editing efficiency profiles for conventional GABA+ and MM-suppressed GABA. This illustrates the editing selectivity of the GABA at 1.9 ppm for both acquisitions. For the MM-suppressed GABA acquisition, inversion at 1.5 ppm results in the 1.7 ppm MM signal being nulled.

FIG. 2

a: Voxel locations the sensorimotor (SM) and occipital (OCC) cortex, images are shown according to radiological convention. b: GABA+ and MMsuppressed GABA spectra from all 12 subjects overlapped for the SM and OCC voxels. The GABA and Glx resonances are labeled.

FIG. 3

Correlation of MM-suppressed GABA measurement with GABA+ measurement for all data (a), the sensorimotor cortex (b), and the occipital cortex (c).