5T‐Based Glutamate Chemical Exchange Saturation Transfer Imaging for Adult Diffuse Glioma Stratification

BACKGROUND: Glutamate chemical exchange saturation transfer (GLU-CEST) is a non-invasive in vivo approach for glutamate detection, but its performance for glioma evaluation at 5T remains incompletely defined. PURPOSE: To investigate factors influencing 5T GLU-CEST and its diagnostic value in glioma stratification. STUDY TYPE: Prospective. PHANTOM AND POPULATION: Five phantom series (pH 6.2-7.4; glutamate 8-20 mM) and 40 adult-type diffuse glioma patients (49.00 ± 12.26 years; 23 males). FIELDSTRENGTH/SEQUENCE: 5 T, fast spin-echo GLU-CEST and amide proton transfer (APT)-CEST. ASSESSMENT: Phantoms and patients underwent MRI scans; GLU-CEST, APT-CEST, and normalized values (ΔGLU-CEST, ΔAPT-CEST) were quantified. Gliomas were graded by WHO 2-4; IDH status was determined. STATISTICAL TESTS: Spearman correlation, Kruskal-Wallis tests, Mann-Whitney U tests, and weighted DeLong tests; two-sided p < 0.05 was significant. RESULTS: GLU-CEST signals positively correlated with glutamate and negatively with pH (ρ ≥ 0.893). Significant differences were found in all effects between WHO Grade 2 and 4 gliomas (ΔGLU-CEST: 2.006 [1.143, 2.799] vs. 4.365 [2.974, 5.299]; GLU-CEST: 7.424 [6.679, 7.649] vs. 10.155 [8.098, 11.550]; ΔAPT-CEST: 1.918 [1.258, 2.461] vs. 3.386 [2.682, 4.805]; APT-CEST: 1.961 [1.425, 2.715] vs. 3.333 [2.478, 4.632]), whereas only ΔGLU-CEST and GLU-CEST exhibited significant disparities between Grade 3 and 4 gliomas (ΔGLU-CEST: 2.171 [1.895, 2.862] vs. 4.365 [2.974, 5.299]; GLU-CEST: 7.102 [6.475, 7.259] vs. 10.155 [8.098, 11.550]). In the solid tumor region, all effects demonstrated significant differences between IDH-mutant and IDH wild-type gliomas (ΔGLU-CEST: 2.111 [1.614, 3.110] vs. 4.333 [2.964, 5.405]; GLU-CEST: 7.259 [6.577, 7.726] vs. 10.291 [8.097, 11.634]; ΔAPT-CEST: 2.017 [1.355, 2.718] vs. 3.235 [2.670, 4.735]; APT-CEST: 2.122 [1.680, 2.889] vs. 3.270 [2.450, 4.262]), whereas GLU-CEST outperformed APT-CEST and ΔAPT-CEST in diagnostic efficacy (AUC difference = 0.073 and 0.101). DATA CONCLUSION: 5 T GLU-CEST is capable of differentiating between grade 2 and grade 4, as well as grade 3 and grade 4 adult diffuse gliomas, and demonstrates superior performance to APT-CEST in the classification of IDH status. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.