Intraoperative Spectroscopic and Mass Spectrometric Assessment of Glioma Margins: A Systematic Review and Meta-Analysis

Background: Maximal safe resection remains a central determinant of outcomes in glioma surgery, yet intraoperative discrimination between tumor and normal brain tissue is limited by the speed and subjectivity of frozen-section analysis. Label-free techniques such as Raman spectroscopy, mass spectrometry (MS), and optical coherence tomography (OCT) offer real-time biochemical and structural characterization that may enhance surgical precision. Their comparative diagnostic accuracy across clinically relevant endpoints has not been comprehensively evaluated. Methods: Following PRISMA 2020 guidelines, a systematic review and quantitative meta-analysis were conducted using PubMed, Embase, Scopus, and Web of Science through December 2024. Original human studies evaluating Raman, MS, or OCT for intraoperative glioma margin assessment were included. Pooled sensitivity, specificity, and diagnostic odds ratios (DORs) were calculated using a random-effects model. Subgroup analyses addressed tumor versus normal brain tissue, infiltrated versus non-infiltrated margins, and IDH-mutant versus wild-type gliomas. Results: Twenty-four studies comprising 1768 patients met the inclusion criteria. Across all modalities, pooled sensitivity and specificity were 0.89 (95% CI 0.86–0.92) and 0.88 (95% CI 0.84–0.91), with a pooled DOR of 65.7 (95% CI 42.3–101.8; logDOR 4.18), indicating high overall discriminative performance. Tumor versus normal differentiation achieved DOR 72.4 (logDOR 4.28; I2 = 26%), infiltrated margin detection DOR 41.8 (logDOR 3.73; I2 = 41%), and IDH classification DOR 52.3 (logDOR 3.96; I2 = 29%). No publication bias was observed. Raman and MS outperformed OCT. Conclusions: Raman spectroscopy, mass spectrometry, and OCT demonstrate strong diagnostic accuracy for real-time intraoperative glioma evaluation, enabling reliable tissue differentiation and molecular profiling that may enhance resection extent and support precision, molecularly informed neurosurgery.