Metabolic and Molecular Correlates of Medulloblastoma: Identification of Molecular Groups Using In Vivo 1H-MR Spectroscopy.
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BACKGROUND: Accurate molecular classification of medulloblastoma is critical for prognosis and treatment planning, but current methods rely on surgical tissue sampling and molecular profiling. This study evaluated whether in vivo proton MR spectroscopy (¹H-MRS) can provide noninvasive metabolic markers to support pre-surgical molecular group stratification. METHODS: In this single-center retrospective study, pre-treatment ¹H-MRS data were analyzed from 95 pediatric patients with medulloblastoma (median age 7.4 years; 56 male). Single-voxel PRESS spectra (TE = 35 ms, TR = 1.5-2.0 s) were acquired during routine clinical MRI, adding approximately 5 minutes of scan time. Absolute metabolite concentrations and selected ratios were quantified using automated spectral fitting. Metabolic profiles were compared across molecular groups (Group 3, n = 22; Group 4, n = 35; SHH, n = 26; WNT, n = 12) and assessed for qualitative concordance with prior ex vivo high-resolution HR-MAS NMR findings. Group differences were tested using Kruskal-Wallis with Dunn post hoc correction. RESULTS: Significant metabolic differences were observed across molecular groups, with strong group effects for taurine, creatine, choline, glutamate, and GABA (all P < .0015). Taurine was elevated in Group 3 and Group 4 relative to SHH (log₂FC = 1.77 and 1.40, adjusted P < 4 × 10⁻⁵). SHH tumors exhibited lower creatine compared with Group 3, Group 4, and WNT (adjusted P < .05). Glutamate was higher in SHH than WNT, while WNT tumors showed increased choline and GABA relative to other groups (adjusted P < .05). In vivo patterns were qualitatively concordant with ex vivo NMR findings. CONCLUSIONS: In vivo ¹H-MRS is a widely available, clinically feasible imaging biomarker that complements existing diagnostics and supports pre-surgical stratification of medulloblastoma.