Shining a light on brain tumors: a review of Raman spectroscopy in the operating room

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.

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.

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.

In vivo multicenter studies report $>85\%$ per-measurement sensitivity and specificity for tumor versus normal classification, with nondestructive analysis in $\sim 2s$ . 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 $\sim 90s$ , though this molecular capability is not clinically validated.

While multicenter studies support the analytic validity of Raman-based tissue detection, clinical adoption requires prospective outcome trials, standardized acquisition protocols, and regulatory advancement.