Quantification of GABA, glutamate and glutamine in a single measurement at 3 T using GABA-edited MEGA-PRESS

Abstract

γ-Aminobutyric acid (GABA) and glutamate (Glu), major neurotransmitters in the brain, are recycled through glutamine (Gln). All three metabolites can be measured by magnetic resonance spectroscopy in vivo, although GABA measurement at 3 T requires an extra editing acquisition, such as Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS). In a GABA-edited MEGA-PRESS spectrum, Glu and Gln co-edit with GABA, providing the possibility to measure all three in one acquisition. In this study, we investigated the reliability of the composite Glu + Gln (Glx) peak estimation and the possibility of Glu and Gln separation in GABA-edited MEGA-PRESS spectra. The data acquired in vivo were used to develop a quality assessment framework which identified MEGA-PRESS spectra in which Glu and Gln could be estimated reliably. Phantoms containing Glu, Gln, GABA and N-acetylaspartate (NAA) at different concentrations were scanned using GABA-edited MEGA-PRESS at 3 T. Fifty-six sets of spectra in five brain regions were acquired from 36 healthy volunteers. Based on the Glu/Gln ratio, data were classified as either within or outside the physiological range. A peak-by-peak quality assessment was performed on all data to investigate whether quality metrics can discriminate between these two classes of spectra. The quality metrics were as follows: the GABA signal-to-noise ratio, the NAA linewidth and the Glx Cramer-Rao lower bound (CRLB). The Glu and Gln concentrations were estimated with precision across all phantoms with a linear relationship between the measured and true concentrations: R¹ = 0.95 for Glu and R¹ = 0.91 for Gln. A quality assessment framework was set based on the criteria necessary for a good GABA-edited MEGA-PRESS spectrum. Simultaneous criteria of NAA linewidth <8 Hz and Glx CRLB <16% were defined as optimum features for reliable Glu and Gln quantification. Glu and Gln can be reliably quantified from GABA-edited MEGA-PRESS acquisitions. However, this reliability should be controlled using the quality assessment methods suggested in this work.

Keywords: GABA; MEGA-PRESS; glutamate; glutamine; quantification.

Figure 1

T ₁‐weighted images showing the positioning of the ¹H magnetic resonance spectroscopy (MRS) voxel in the left occipital cortex (a), left motor cortex (b), right motor cortex (c), anterior cingulate cortex (d) and occipital cortex (e). (f) Diagram of the Mescher–Garwood point‐resolved spectroscopy (MEGA‐PRESS) pulse sequences used in this study

Figure 2

Workflow of this study. CRLB, Cramer–Rao lower bound; GABA, γ‐aminobutyric acid; Gln, glutamine; Glu, glutamate; Glx, Glu + Gln; LW, linewidth; NAA, N‐acetylaspartate; SD, standard deviation; SNR, signal‐to‐noise ratio

Figure 3

Glutamate (blue) and glutamine (red) spectra acquired from 25mM concentration phantoms

Figure 4

The area under the peak at 3.75 ppm, the Glx (Glu + Gln) peak, versus the glutamate (Glu) + glutamine (Gln) concentration present in the phantoms. The area under the peak at 3.75 ppm was quantified with AMARES

Figure 5

The ratio of glutamate (Glu) (a) and glutamine (Gln) (b) over N‐acetylaspartate (NAA) concentration quantified using QUEST in phantoms versus the known concentration. The slope of the line is the reciprocal of the concentration calibration coefficient (CC_m)

Figure 6

An example of a spectrum in vivo and its fitting. QUEST is used for concentration calculation. The individual components of the spectra glutamine (Gln), glutamate (Glu), γ‐aminobutyric acid (GABA), N‐acetylaspartate (NAA) and the residual are illustrated. The AMARES fit is used for quality assessment

Figure 7

(a–c) Examples of glutamate (Glu) and glutamine (Gln) fitting in spectra in vivo which failed one or two checks in the quality assessment. The upper trace is the original data and the QUEST fits of Glu and Gln are presented below. The quality assessment values calculated using AMARES are reported for each spectrum; the text in red indicates the failed quality parameter. (d) Sample of a spectrum and its Glu and Gln fit which passed all the quality criteria checks. CRLB, Cramer–Rao lower bound; GABA, γ‐aminobutyric acid; Glx, Glu + Gln; LW, linewidth; NAA, N‐acetylaspartate; SNR, signal‐to‐noise ratio

Figure 8

Scatter plots of the three quality assessments: Glx (glutamate + glutamine) Cramer–Rao lower bound (CRLB), N‐acetylaspartate (NAA) linewidth and γ‐aminobutyric acid (GABA) signal‐to‐noise ratio (SNR) are illustrated in both the physiological (Phys.) and non‐physiological (Non‐phys.) classes of data. The broken line is the rejection threshold

Figure 9

Plot of all the data points and their ratio of glutamate to glutamine (Glu/Gln). The triangles represent the data that failed the quality criteria and the crosses are those that passed. The broken line indicates the Glu/Gln ratios of 1.5 and 4.5