SIGNAL: A Scalable, Real-World Model for Rapid Intraoperative Molecular Classification of Gliomas Using Stimulated Raman Histology

BackgroundPrevious machine learning models to intraoperatively predict the molecular status of gliomas using stimulated Raman histology (SRH), such as DeepGlioma, have achieved high performance (91.5% accuracy) on curated datasets. However, when used intraoperatively, DeepGlioma (162M parameters) runs slowly on current SRH hardware and underperforms due to its lack of an image rejection mechanism and its validation on curated images. Here, we introduce SRH-Informed Glioma classificatioN with Attention Learning (SIGNAL) (27M parameters), a lighter model with a built-in attention-based rejection mechanism that outperforms DeepGlioma on uncurated clinical datasets. MethodsSIGNAL was developed using 1.56 million SRH fields-of-view from 967 adult diffuse glioma patients collected between December 2017 and July 2025. We used 412 patients from NYU for training and internal validation and a multi-institutional, international cohort of 555 patients for testing. SIGNAL uses a ResNet50 backbone pretrained using a hierarchical contrastive loss function followed by a multi-head multi-layer perceptron (MLP). Using a patch-based attention threshold of 0.6, a final MLP was trained to predict glioma subtypes: glioblastoma, oligodendroglioma, or astrocytoma. ResultsSIGNAL outperformed DeepGlioma, achieving greater overall accuracy (90.10% vs. 72.59%) while running faster (16.0 vs. 6.7 patches/s). SIGNAL also outperformed DeepGlioma on all three molecular classification tasks, including IDH mutation (accuracy: 93.51% vs. 79.22%), 1p19q codeletion (93.51% vs. 88.31%), and ATRX loss (89.61% vs. 83.98%). SIGNALs attention mechanism had a strong positive linear correlation with mean patch cellularity (r=0.96, p<0.001) and a strong negative correlation with patch blood coverage (r=-0.99,p<0.001). Finally, subtype and molecular accuracy between tumor core and margin samples were equivalent despite significantly lower patch retention in tumor margins (44.5% vs 60.2%, p<0.0001). ConclusionSIGNAL is a lightweight model for intraoperative molecular classification of gliomas using SRH imaging. Its attention-based image quality filter allows for excellent performance, quick processing, and highly interpretable outputs critical for reliable use in intraoperative workflows. Brief 1-2 Sentence DescriptionWe present SIGNAL, a lightweight machine learning model for intraoperative molecular classification of diffuse gliomas using stimulated Raman histology, whose core innovation is a learned attention mechanism that filters diagnostically uninformative tissue, such as blood and acellular regions, before classification, enabling robust real-world generalizability. Validated on 555 patients across four international centers, SIGNAL outperforms the previous state-of-the-art model DeepGlioma on glioma subtype classification (90.10% vs. 72.59% accuracy) while running 2.4 times faster on intraoperative hardware.