Abstract
Abstract
Background
Glutamatergic dysregulation contributes to neurodegenerative and neuro-oncological disease. However, in vivo measurement of glutamate (Glu) at widely available 3 T clinical field strengths is complicated by spectral overlap with glutamine (Gln). We evaluated singlet-filtered proton magnetic resonance spectroscopy with optimal-control pulses (SFOC-MRS) for phantom-calibrated apparent Glu quantification at 3 T, characterised regional values in healthy adults, and applied the workflow in newly diagnosed glioma.
Methods
In this prospective, single-centre observational study, we applied SFOC-MRS to selectively isolate and quantify Glu at 3 T, with conventional short-echo point-resolved spectroscopy (PRESS) acquired in the same session as a clinical reference. Phantom-calibrated apparent [Glu] was derived from a six-point external L-glutamate phantom calibration. Twenty-five healthy adults (sampling three predefined regions: frontal lobe, occipital lobe, and basal ganglia) and 15 patients with treatment-naïve supratentorial glioma (sampling solid tumour, peritumoural oedema, and contralateral frontal lobe) underwent single-voxel acquisitions. Group comparisons used Welch's heteroscedastic analysis of variance (ANOVA) and t-tests with Holm correction; effect sizes are reported as Hedges' g.
Results
SFOC-MRS resolved the Glu triplet at approximately 2.35 ppm with linear phantom calibration (R² = 0.974). In healthy adults, apparent [Glu] followed a regional hierarchy (frontal lobe 8.50 ± 1.98 mM > occipital lobe 4.79 ± 1.51 mM > basal ganglia 3.24 ± 0.82 mM; Welch's ANOVA p = 4.2 × 10⁻¹²; Hedges' g = 3.06 for frontal vs basal ganglia). In glioma, pronounced compartmental heterogeneity emerged (Welch's ANOVA p = 0.0013), with peritumoural oedema substantially lower than both solid tumour and the contralateral frontal lobe (both Holm p = 9.3 × 10⁻³). Glioma-related voxels showed significantly lower [Glu] than frontal- and occipital-lobe voxels in healthy controls (3.75 ± 2.93 vs 7.06 ± 2.56 mM; Welch's t = 4.14; p = 2.8 × 10
− 4
; Hedges' g = 1.22).
Conclusions
At 3 T, SFOC-MRS yielded a selective, phantom-calibrated apparent Glu measure and detected regional and glioma-compartment differences. Further test–retest, multi-volume phantom, tissue-correction, and multicentre validation is required before clinical deployment.