Abstract
γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter, is challenging to measure using proton spectroscopy due to its relatively low concentration, J-coupling and overlapping signals from other metabolites. Currently, the prevalent methods for detecting GABA at ultrahigh field strengths (≥ 7 T) are GABA-editing and model fitting of non-editing single voxel spectra. These two acquisition approaches have their own advantages: the GABA editing approach directly measures the GABA resonance at 3 ppm, whereas the fitting approach on the non-editing spectrum allows the detection of multiple metabolites, and has an SNR advantage over longer echo time (TE) acquisitions. This study aims to compare these approaches for estimating GABA at 7 T. We use an interleaved sequence of semi-LASER (sLASER: TE = 38 ms) and MEGA-sLASER (TE = 80 ms). This simultaneous interleaved acquisition minimizes the differential effect of extraneous factors, and enables an accurate comparison of the two acquisition methods. Spectra were acquired with an 8 ml isotropic voxel at six different brain regions: anterior-cingulate cortex, dorsolateral-prefrontal cortex, motor cortex, occipital cortex, posterior cingulate cortex, and precuneus. Spectral fitting with LCModel quantified the GABA to total Cr (tCr: Creatine + Phosphocreatine) concentration ratio. After correcting the T2 relaxation time variation, GABA/tCr ratios were similar between the two acquisition approaches. GABA editing showed smaller spectral fitting error according to Cramér–Rao lower bound than the sLASER approach for all regions examined. We conclude that both acquisition methods show similar accuracy but the precision of the MEGA-editing approach is higher for GABA measurement. In addition, the 2.28 ppm GABA resonance was found to be important for estimating GABA concentration without macromolecule contamination in the GABA-edited acquisition, when utilizing spectral fitting with LCModel.
Highlights
Introduction γAminobutyric acid (GABA), the major inhibitory neurotransmitter, is present at about one millimolar concentration in the human brain [1]
We found a linear correlation between the GABA/total Cr (tCr) concentration ratio and GM tissue distribution
These regression lines were almost identical for the two methods. This result shows a large dependence of measured GABA concentration on GM volume fraction, independent of the two acquisition methods
Summary
Introduction γAminobutyric acid (GABA), the major inhibitory neurotransmitter, is present at about one millimolar concentration in the human brain [1]. Existing in-vivo approaches for measuring GABA include positron emission tomography (PET) [8], single photon emission tomography (SPECT) [9], proton magnetic resonance spectroscopy (1H MRS) [10] and chemical exchange saturation transfer (CEST) [11, 12]. MRS at ultrahigh filed (UHF 7 T) is widely used due to high sensitivity and specificity for measuring GABA [13]. GABA MRS is still challenging by reason of its low concentration and resonances overlapping with higher concentration signals [14]. Various acquisition strategies for proton MRS have been proposed for measuring GABA, such as J-editing [15] (e.g. MEGA-PRESS (MEsher-GArwood Point RESolved Spectroscopy) [16, 17]) and double quantum filters [18]
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