Diagnostic Utility of Intratumoral Susceptibility Signals in Adult Diffuse Gliomas: Tumor Grade Prediction and Correlation with Molecular Markers Within the WHO CNS5 (2021) Classification

Background/Objectives: This study evaluates intratumoral susceptibility signals (ITSS) as imaging markers for glioma grade prediction and their association with molecular and histopathologic features, in the context of the fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS5). Methods: We retrospectively analyzed patients with adult diffuse gliomas who underwent pretreatment magnetic resonance imaging. ITSS were semiquantitatively graded by two radiologists: grade 0 (no signal), grade 1 (1–5), grade 2 (6–10), and grade 3 (≥11). Relative cerebral blood volume (rCBV) and tumor volume were also obtained. Histopathologic features included tumor grade, Ki-67, mitotic count, necrosis, microvascular proliferation, and molecular alterations (isocitrate dehydrogenase [IDH], 1p/19q, cyclin-dependent kinase inhibitors 2A and 2B [CDKN2A/B], and p53). Regression models predicted tumor grade (low: 1–2, high: 3–4) using ITSS, tumor volume, and rCBV. ROC curves and diagnostic performance metrics were analyzed. Results: 99 patients were included. ITSS grading correlated with rCBV, tumor volume, mitotic count, Ki-67, and tumor grade (p < 0.001). ITSS grades 0–1 were associated with oligodendrogliomas and astrocytomas (p < 0.001), IDH mutations (p < 0.001), and 1p/19q co-deletions (p = 0.01). ITSS grades 2–3 were linked to glioblastomas (p < 0.001), necrosis (p < 0.001), microvascular proliferation (p < 0.001), and CDKN2A/B homozygous deletions (p = 0.02). Models combining ITSS with rCBV and volume showed AUC of 0.94 and 0.96 (p < 0.001), outperforming univariate models. Conclusions: Semiquantitative ITSS grading correlates with key histopathologic and molecular glioma features. Combined with perfusion and volumetric parameters, ITSS enhance non-invasive glioma grading, in alignment with WHO CNS5.