Abstract
PurposeThe aim of the study was to develop and validate a new localized 1H MRS pulse sequence and automated post-processing software for the quantification of brain Glutamate (Glu) in clinical conditions at 7.0T in order to get reliable and reproducible results for acute intervention studies.MethodsHere we describe a new localized proton MRS method “Fully Automated MacrOmolecUle Suppressed Single Voxel Glutamate Spectroscopy (FAMOUS SVGS)” for measuring Glu. FAMOUS SVGS method consists of a new pulse sequence with optimized switchable water, metabolites and outer volume suppression modules, as well as a frequency selective inversion pulse and automated post-processing of the five spectra obtained. FAMOUS SVGS method was first validated with glutamate phantoms and then validated with test–retest repeatability studies in the occipital cortex of five normal volunteers at 7.0T.ResultsGlutamate concentrations estimated from phantoms with FAMOUS SVGS method correlated well with actual concentrations. Test–retest repeatability studies in human brain in vivo yielded less than 0.3 mM intra-subject variations in Glu concentrations.ConclusionsFAMOUS SVGS method enables Glu quantification in vivo at 7.0T with test–retest variability of less than 0.3 mM. We expect that we can reliably measure ≥0.5 mM change in glutamate due to any acute intervention.
Highlights
Glutamate (Glu) is a major excitatory neurotransmitter that is present in abundance in the synaptic vesicles of the human brain [1]
We demonstrate a new method for quantification of the Glu at 2.35 ppm from the Fully Automated MacrOmolecUle Suppressed Single Voxel Glutamate Spectroscopy (FAMOUS single voxel glutamate spectroscopy (SVGS))
The concentration of glutamate from the voxel positioned on the glutamate monosodium phantom, as shown in Fig. 4, from the FAMOUS SVGS shows a good linear correlation between the actual and measured glutamate concentrations
Summary
Glutamate (Glu) is a major excitatory neurotransmitter that is present in abundance in the synaptic vesicles of the human brain [1] It plays an important role in the day-to-day functions such as cognitive, learning and memory, a key metabolite in cellular metabolism, and helps in removal of ammonia from the body. Its quantification has gained significant importance due to its implications in many of the neuropsychological as well as neurodegenerative disorders In these brain disorders, as the changes in the Glu levels are expected to be relatively small, it is important to have a non-invasive method that measures these small changes in Glu concentration with high degree of accuracy and repeatability. Based on literature reports and from our own experience, we feel the following issues might contribute to the glutamate quantification errors: (i) Eddy currents, Nanga et al J Transl Med (2016) 14:220
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