Reliability of 7T 1H-MRS Measured Human Prefrontal Cortex Glutamate, Glutamine, and Glutathione Signals Using an Adapted Echo Time Optimized PRESS Sequence: A Between- and Within-Sessions Investigation

Purpose: To ascertain the mechanisms of neuropsychiatric illnesses and their treatment, accurate and reliable imaging techniques are required; proton magnetic resonance spectroscopy (H-1-MRS) can noninvasively measure glutamatergic function. Evidence suggests that aberrant glutamatergic signaling plays a role in numerous psychopathologies. Until recently, overlapping glutamatergic signals (glutamate, glutamine, and glutathione) could not easily be separated. However, the advent of novel pulse sequences and higher field magnetic resonance imaging (MRI) allows more precise resolution of overlapping glutamatergic signals, although the question of signal reliability remains undetermined. Materials and Methods: At 7T MR, we acquired H-1-MRS data from the medial pregenual anterior cingulate cortex of healthy volunteers (n=26) twice on two separate days. An adapted echo time optimized point-resolved spectroscopy sequence, modified with the addition of a J-suppression pulse to attenuate N-acetyl-aspartate multiplet signals at 2.49 ppm, was used to excite and acquire the spectra. In-house software was used to model glutamate, glutamine, and glutathione, among other metabolites, referenced to creatine. Intraclass correlation coefficients (ICCs) were computed for within- and between-session measurements. Results: Within-session measurements of glutamate, glutamine, and glutathione were on average reliable (ICCs 0.7). As anticipated, ICCs for between-session values of glutamate, glutamine, and glutathione were slightly lower but nevertheless reliable (ICC >0.62). A negative correlation was observed between glutathione concentration and age (r((24))=-0.37; P<0.05), and a gender effect was noted on glutamine and glutathione. Conclusion: The adapted sequence provides good reliability to measure glutamate, glutamine, and glutathione signals.