The Utility of Cystathionine Assessment Using Proton MRS for the Preoperative Differential Diagnosis of Adult-Type...

Adult-type diffuse gliomas-astrocytoma, isocitrate dehydrogenase (IDH)-mutant; oligodendroglioma, IDH-mutant and 1p/19q-codeleted; and glioblastoma, IDH-wild-type-have distinct prognoses and treatment responses. Accurate preoperative subtype estimation is, therefore, important for clinical decision-making. Proton MR spectroscopy (¹H-MRS) enables noninvasive assessment of tumor metabolism. Cystathionine, detectable at 2.72 ppm, has been proposed as a metabolic marker of oligodendroglioma, but its diagnostic performance across adult-type diffuse gliomas remains incompletely defined. This study evaluated the utility of cystathionine quantification by ¹H-MRS for differentiating glioma subtypes and assessed whether combined analysis with 2-hydroxyglutarate (2HG) improves diagnostic performance.

Eighty-five patients with histologically and molecularly confirmed adult-type diffuse gliomas (25 oligodendrogliomas, 28 astrocytomas, 32 glioblastomas) underwent preoperative 3T MRI including the single-voxel point-resolved spectroscopy sequence for ¹H-MRS (TE = 97 ms). Spectra with severe artifacts were excluded; no cases were excluded on the basis of full width at half maximum (FWHM < 12.8 Hz, 0.1 ppm at 3T). Metabolites were quantified using LCModel, with concentrations normalized to the unsuppressed water signal and relaxation-corrected. Group comparisons of cystathionine levels were performed using Kruskal-Wallis and Bonferroni-corrected pair-wise tests. The receiver operating characteristic analysis evaluated diagnostic performance for differentiating oligodendrogliomas from astrocytomas and glioblastomas. Supplementary analyses excluding spectra with cystathionine Cramér-Rao lower bounds (CRLB) ≥ 50% and combined cystathionine-2HG receiver operating characteristic were also performed.

Cystathionine levels were highest in oligodendrogliomas (mean, 1.040 [SD, 0.908] mM), intermediate in glioblastomas, and lowest in astrocytomas (mean, 0.437 [SD, 0.403] mM). Oligodendrogliomas showed significantly higher levels than astrocytomas (P = .003), whereas no significant difference was observed between oligodendrogliomas and glioblastomas. Receiver operating characteristic analysis showed moderate diagnostic performance (area under the curve [AUC] = 0.69 for oligodendroglioma vs astrocytoma; AUC = 0.56 for oligodendroglioma vs glioblastoma). After CRLB-based exclusion, sensitivity increased but specificity decreased (AUC = 0.83 for oligodendroglioma vs astrocytoma). Combining cystathionine with 2HG modestly improved AUCs (0.72 and 0.61, respectively).

Cystathionine quantification by ¹H-MRS reflects biologically meaningful metabolic differences among adult-type diffuse gliomas, with higher levels characteristic of oligodendrogliomas compared with astrocytomas. However, overlap with glioblastomas limits its role as a stand-alone discriminator. When interpreted alongside 2HG and conventional imaging features, cystathionine may serve as a supportive metabolic marker to enhance preoperative glioma subtype classification.