Abstract
BACKGROUND: Glutamate and glutamine are critical metabolites in gliomas, each serving distinct roles in tumor biology. Separate quantification of these metabolites using in vivo MR spectroscopy (MRS) at clinical field strengths (≤ 3T) is hindered by their molecular similarity, resulting in overlapping, hence indistinguishable, spectral peaks. PURPOSE: To develop an MRS imaging (MRSI) protocol to map glutamate and glutamine separately at 3T within clinically feasible time, using J-modulation to enhance spectral differentiation, demonstrate its reliability/reproducibility, and quantify the metabolites in glioma subregions. STUDY TYPE: Prospective. POPULATION: Phantoms, 5 healthy subjects, and 30 patients with suspected glioma. IDH wild-type glioblastoma cases were evaluated to establish a uniform group. FIELD STRENGTH/SEQUENCE: 3T, Research protocol: 2D (1)H sLASER MRSI (40 and 120 ms TE) with water reference, 3D T1-weighted and 2D T2-weighted. Trial-screening process: T1-weighted, T1-weighted contrast-enhanced, T2-weighted, FLAIR. ASSESSMENT: Spectral simulations and phantom measurements were performed to design and validate the protocol. Spectral quality/fitting parameters for scan-rescan measurements were obtained using LCModel. The proposed long-TE data were compared with short-TE data. BraTS Toolkit was employed for fully automated tumor segmentation. STATISTICAL TESTS: Scan-rescan comparison was performed using Bland-Altman analysis. LCModel coefficient of modeling covariance (CMC) between glutamate and glutamine was mapped to evaluate their model interactions for each spectral fitting. Metabolite levels in tumor subregions were compared using one-way ANOVA and Kruskal-Wallis. A p value < 0.05 was considered statistically significant. RESULTS: Spectral quality/fitting parameters and metabolite levels were highly consistent between scan-rescan measurements. A negative association between glutamate and glutamine models at short TE (CMC = -0.16 ± 0.06) was eliminated at long TE (0.01 ± 0.05). Low glutamate in tumor subregions (non-enhancing-tumor-core: 5.35 ± 4.45 mM, surrounding-non-enhancing-FLAIR-hyperintensity: 7.39 ± 2.62 mM, and enhancing-tumor: 7.60 ± 4.16 mM) was found compared to contralateral (10.84 ± 2.94 mM), whereas glutamine was higher in surrounding-non-enhancing-FLAIR-hyperintensity (9.17 ± 6.84 mM) and enhancing-tumor (7.20 ± 4.42 mM), but not in non-enhancing-tumor-core (4.92 ± 3.38 mM, p = 0.18) compared to contralateral (2.94 ± 1.35 mM). DATA CONCLUSION: The proposed MRSI protocol (~12 min) enables separate mapping of glutamate and glutamine reliably along with other MRS-detectable standard metabolites in glioma subregions at 3T. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.