Machine Learning-Based Fluorescence Assessment for Augmented Imaging and Decision Support in Glioblastoma Resections

Background/Objectives: Glioblastoma is the most common and aggressive primary malignant brain tumor in adults, characterized by infiltrative growth and poor prognosis. Achieving maximal resection without inducing neurological deficits remains a challenge in glioblastoma surgery. While 5-aminolevulinic acid-based fluorescence-guided surgery supports intraoperative tumor visualization, its reliability is limited by patient variability and weak fluorescence signals. This study proposes a machine learning framework to enhance fluorescence-guided surgery sensitivity by analyzing surgical microscope images at the pixel level. Methods: Fluorescence-mode neurosurgical microscope images of synthetic samples with known Protoporphyrin IX (PPIX) concentrations were used to train three classifiers (Support Vector Machine, Naïve Bayes, Neural Network) for pixel-wise fluorescence detection. In parallel, three contrastive-learning-based Variational Autoencoders (VAE, $\beta$ = 1, 2, 3) were evaluated for detecting weak fluorescence beyond visual perception. Additionally, a regression model was trained to relate pixel features to PPIX concentration. The best-performing VAE ($\beta$ = 1) was subsequently trained on real intraoperative data, and its detection sensitivity was compared to annotations from four experienced surgeons. Results: The proposed model achieved the highest detection rates on synthetic test data when calibrated for 99% specificity. Applied to real intraoperative images, the model revealed fluorescent areas substantially larger than those marked by experienced surgeons. In non-5-ALA control cases, minimal false positives were observed, indicating a specificity exceeding 99.9%. The regression model reliably quantified PPIX concentration in synthetic samples ($R^2=0.92$). Conclusions: By enabling more sensitive and objective fluorescence detection, this approach offers a valuable tool for improving surgical decision-making and facilitating safer, more extensive tumor resections.