Localized MRS reliability of in vivo glutamate at 3 T in shortened scan times: a feasibility study

Glutamate is the prime excitatory neurotransmitter in the mammalian brain and has been implicated in a wide range of psychiatric conditions. To improve the applicability and clinical reach of magnetic resonance spectroscopy (MRS), research is needed to develop shortened, yet reliable, MRS scanning procedures for standard 1.5-3-T clinical magnetic resonance imaging (MRI) systems, particularly with young or vulnerable populations unable to tolerate longer protocols. To this end, we evaluated the test-retest reliability of a shortened J-resolved MRS sequence in healthy adolescents (n = 22) aged 12-14 years. Participants underwent a series of sequential 6-min MRS scans, with the participants remaining in situ between successive scans. Glutamate and other metabolites were acquired from the rostral anterior cingulate cortex, as glutamatergic function in this region has been implicated in a number of psychiatric illnesses. Thirteen neurochemicals were quantified as ratios to total creatine, and reliability scores were expressed as the percentage difference between the two scans for each metabolite. Test-retest assessment of glutamate was reliable, as scores were less than 10% different (7.1 ± 4.2%), and glutamate values across scans were significantly correlated (Pearson r = 0.680, p < 10^-4 ). Several other neurochemicals demonstrated satisfactory reliability, including choline (Cho) (7.4 ± 5.6%), glutathione (GSH) (8.6 ± 4.1%), myo-inositol (mI) (6.5 ± 7.1%) and N-acetylaspartate (NAA) (3.5 ± 3.6%), with test-retest correlations ranging from 0.747 to 0.953. A number of metabolites, however, did not demonstrate acceptable test-retest reliability using the current J-resolved MRS sequence, ranging from 13.8 ± 13.7% (aspartate, Asp) to 45.9 ± 38.3% (glycine, Gly). Collectively, test-retest analyses suggest that clinically viable quantitative data can be obtained on standard MRI systems for glutamate, as well as the other metabolites, during short scan times in a traditionally challenging brain region.