Shining a Light on Brain Tumors: a Review of Raman Spectroscopy in the Operating Room

Significance:Maximizing brain tumor resection while preserving neurological function remains a neurosurgical challenge. Current intraoperative tools, including MRI, ultrasound, and frozen section, disrupt workflow and provide limited real-time molecular information. Aim:This review synthesizes evidence for Raman spectroscopy as an intraoperative tool in glioma and brain metastasis surgery, comparing it against established alternatives and framing findings within a diagnostic hierarchy from analytic validity through clinical utility to outcome benefit. Approach:Evidence is arranged by surgical setting: in vivo handheld fiber-optic probes and ex vivo platforms including Raman microscopy, stimulated Raman scattering (SRS) imaging, and visible resonance Raman. Results:In vivo multicenter studies report > 85 % per-measurement sensitivity and specificity for tumor versus normal classification, with nondestructive analysis in ∼ 2    s . Molecular marker detection, including IDH mutation status, has been demonstrated predominantly ex vivo. Ex vivo SRS generates histology-quality images and can classify selected molecular alterations within ∼ 90    s , though this molecular capability is not clinically validated. Conclusions:While multicenter studies support the analytic validity of Raman-based tissue detection, clinical adoption requires prospective outcome trials, standardized acquisition protocols, and regulatory advancement.