Intratumoral susceptibility signals on susceptibility-weighted imaging for glioma grading and molecular profiling: a systematic review and meta-analysis

BACKGROUND: Intratumoral susceptibility signals on susceptibility-weighted imaging have emerged as a potential biomarker for glioma grading and molecular characterization. PURPOSE: To evaluate the diagnostic performance of intratumoral susceptibility signals for glioma grading using harmonized World Health Organization grade contrasts. DATA SOURCES: PubMed, Embase, and Cochrane were searched from inception through December 18, 2025. STUDY SELECTION: Studies reporting preoperative semiquantitative assessment of intratumoral susceptibility signals in histologically confirmed gliomas were included; grading reference standards ranged from histology-based to integrated 2021 World Health Organization histomolecular diagnosis. DATA ANALYSIS: The primary analysis compared World Health Organization grades III-IV with grade II. Alternative contrasts were analyzed separately. Threshold-specific sensitivity and specificity were pooled when at least 3 comparable studies were available. Observed-only and leave-one-out analyses assessed robustness. DATA SYNTHESIS: Nineteen studies including 1383 patients were included; 10 contributed to quantitative grading analyses. For World Health Organization grade III-IV versus II, pooled sensitivity and specificity were 0.96 (95% CI, 0.86-0.99) and 0.48 (0.22-0.75) at an intratumoral susceptibility signal threshold ≥1, 0.85 (0.74-0.91) and 0.93 (0.84-0.97) at threshold ≥2, and 0.72 (0.59-0.82) and 0.97 (0.93-0.99) at threshold ≥3. Molecular findings were heterogeneous and summarized descriptively, with higher intratumoral susceptibility signal burden most consistently associated with isocitrate dehydrogenase wild-type status. LIMITATIONS: Studies were predominantly retrospective and single-center, with heterogeneous intratumoral susceptibility signal scoring, imaging protocols, and World Health Organization reference standards. Some contingency tables required reconstruction. CONCLUSIONS: Intratumoral susceptibility signals showed threshold-dependent performance for distinguishing World Health Organization grade III-IV from grade II gliomas. Among the prespecified ordinal thresholds, a threshold ≥2 provided the most balanced sensitivity-specificity profile. Molecular evidence remains exploratory.