INTRAOPERATIVE MOLECULAR IMAGING OF GLIOMA MARGINS: COMPARATIVE INTEGRATION OF 5-AMINOLEVULINIC ACID, RAMAN SPECTROSCOPY, AND REAL-TIME TISSUE CLASSIFICATION

Аннотация

Background. In high-grade and molecularly heterogeneous diffuse gliomas, neurosurgical decisions remain difficult because visual inspection and white-light microscopy underestimate infiltrative tumor, whereas fluorescence intensity varies with tumor biology, treatment history, pharmacokinetics, and optical conditions.

Materials and methods. A structured narrative review is proposed using clinical trials, prospective cohorts, diagnostic-accuracy studies, systematic reviews, and relevant technical investigations. Evidence is organized by biological plausibility, technical performance, patient selection, safety, clinical effectiveness, reproducibility, and implementation. A prospective comparative study is specified for adults undergoing resection of newly diagnosed or recurrent contrast-enhancing diffuse glioma, with 5-ALA fluorescence-guided surgery alone as the reference strategy.

Results. The synthesis addresses five domains: fluorescence-guided resection, spectroscopic detection of nonfluorescent infiltration, real-time tissue classification, sampling bias and histological ground truth, workflow and regulatory translation. The proposed primary endpoint is patient-level sensitivity for viable infiltrating tumor at the final resection margin without an increase in permanent neurological morbidity; secondary endpoints include specificity, positive predictive value, residual enhancing volume, sampling time, interobserver agreement, molecular subgroup performance, and cost per additional tumor-positive margin detected. Originality derives from linking technical accuracy to patient-centered outcomes, explicitly modeling uncertainty, and requiring external validation.

Conclusion. Standardized endpoints support reliable clinical comparison. Independent adjudication strengthens causal interpretation. Longitudinal follow-up clarifies therapeutic durability. Equity analysis supports responsible implementation. Transparent reporting improves scientific reproducibility. Patient safety remains the central priority. External datasets reduce optimistic performance estimates. Rigorous independent external validation remains essential.