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: R 1 = 0.95 for Glu and R 1 = 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.

Altered GABA Concentration in Brain Motor Area Is Associated with the Severity of Motor Disabilities in Individuals with Autism Spectrum Disorder

“…Furthermore, TE = 70 ms has been reported to successfully acquire GABA signal using MEGA-PRESS in Siemens system (Hattingen et al 2014;Sanaei Nezhad et al 2018;Vega et al 2014). A frequency-selective editing pulse was applied at 1.9 ppm (ON) and 7.5 ppm (OFF) in alternating spectral lines to differently refocus the GABA triplet signal at 3.02 ppm.…”

Number of subjects required in common study designs for functional GABA magnetic resonance spectroscopy in the human brain at 3 Tesla

“…It is worth stating that this region is particularly hard to shim due to its proximity to the sinus. Note that only data from the ACC and OCC pass the strict spectral quality test as set out in (Sanaei Nezhad et al, ), that is SNR > 1.0, NAA linewidth < 8 Hz and Glx CRLB < 16%. These limits are suggested for quantification of Glutamate and Glutamine and so may be too strict for accurate assessment of GABA but nevertheless serve as a guide for very high‐quality data.…”

“…LMC, LOCC and RMC voxels had 32 dynamics in total (acquisition time 4 min 16 s); ACC, ATL, OCC had 74 dynamics in total (acquisition time 9 min 52 s). The water suppression method had an excitation with a window of 140 Hz, and the shimming was second‐order pencil beam (FASTMAP), as described previously (Sanaei Nezhad et al, ). The N‐acetylaspartate (NAA) peak at 2.02 ppm was used for frequency referencing.…”

“…All spectra were subjected to quality control assessment as per (Sanaei Nezhad et al, ). Briefly, GABA SNR, NAA linewidth and Glx Cramer–Rao lower bound (CRLB) were calculated for every data set with an acquisition duration of 4 min 16 s of data and the spectra passed quality control if the following conditions were met: NAA linewidth and Glx CRLB are both less than the mean plus 2 standard deviations of all the data within that region. GABA SNR is greater than the mean minus 2 standard deviations of all data within that region. …”

“…Note that each spectrum is judged on the basis of the average data quality within the region it was acquired, rather than using the cut‐offs suggested in Sanaei Nezhad et al (). This was implemented to provide sample size information for both high‐ and low‐quality data.…”