Synopsis

Brain function is largely controlled by inhibitory processes steered by main inhibitory neurotransmitter GABA. In this role, GABA is essential in brain development and plasticity as well as neuropsychiatric and neurodegenerative diseases. In order to accurately measure GABA responsiveness, we designed a bilateral edited fMRS sequence including real-time frequency and motion correction, as the relatively weak GABA signal is highly susceptible to frequency drift and motion. As acquisition of the macromolecule-uncontaminated GABA signal is challenging at lower field strengths, experiments were performed at 7T.

Purpose

Introduction

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and essential in shaping and controlling neurotransmission. Dysfunctional GABA is suggested to be involved in neuropsychiatric and neurodegenerative diseases. The pure GABA signal, i.e. free from macromolecule contamination, is challenging to assess at lower field strengths, but at 7T the uncontaminated GABA signal can be acquired robustly using the MEGA-sLASER sequence [1]. Using a dual-voxel [2] functional paradigm, it is possible to investigate GABA responsiveness in the stimulated brain area as well as contralateral brain area. As the relatively weak GABA signal is highly susceptible to frequency drift [3] and motion, which are likely to occur during a functional paradigm, real-time frequency and motion correction were added to the sequence.

The 3.0 ppm resonance of GABA is coupled to its 1.9 ppm resonance. In Mescher-Garwood (MEGA) editing [4], a refocusing pulse is applied to the coupled resonance in the even acquisitions (edit-on) while in the odd acquisitions J-coupling is not refocused (edit-off). Subtraction of the edit-on and edit-off spectra results in the edited spectrum with a resolved GABA resonance at 3.0 ppm. The co-edited macromolecule resonance at 3.0 ppm can be suppressed by applying refocusing pulses symmetrically around the coupled 1.7 ppm resonance, alternating between 1.9 (edit-on) and 1.5 ppm (edit-off) [5].

Methods

MRS experiments were performed with a 7T MR scanner (Philips, Best, The Netherlands) in combination with a dual transmit coil and a 32-channel receive head coil (Nova Medical, Wilmington, MA, USA). Motion tracking was performed using volumetric 3D EPI navigators [6] that were interleaved before water suppression in every MRS acquisition, using an interleaved scanning framework [7,8]. Acquisitions were discarded afterwards if motion exceeded 1 mm based on the registered navigators. A frequency drift measurement was performed prior to each 3D EPI volume by readouts of the central k-space line.

Prior to MRS, T₁-weighted MPRAGE (1 mm isotropic resolution, 4 min scan time) and functional MRI (2 mm resolution, 2 min scan time) sequences were performed for voxel placement purposes. To identify the activated brain area, volunteers underwent an fMRI sequence. The task paradigm consisted of three cycles of twenty acquisitions, of which ten acquisitions rest and ten acquisitions of right hand-clenching. Based on the fMRI activation map, 20x20x20 mm³ MRS voxels were placed covering the activated brain area and the contralateral brain area (Fig.1). During fMRS (MEGA-sLASER, 320 acquisitions, TR/TE=3500/74 ms), a rest period of eighty acquisitions was followed by a task period of 160 acquisitions and again a rest period of eighty acquisitions.

Measurements were performed according to the local ethical protocols.

Results

Discussion

Acknowledgements

References

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