Focus on Focus: Focus-oriented Representation Learning and Multi-view Cross-modal Alignment for Glioma Grading

Recently, multimodal deep learning, which integrates histopathology slides and molecular biomarkers, has achieved a promising performance in glioma grading. Despite great progress, due to the intra-modality complexity and intermodality heterogeneity, existing studies suffer from inadequate histopathology representation learning and inefficient molecular-pathology knowledge alignment. These two issues hinder existing methods to precisely interpret diagnostic molecular-pathology features, thereby limiting their grading performance. Moreover, the real-world applicability of existing multimodal approaches is significantly restricted as molecular biomarkers are not always available during clinical deployment. To address these problems, we introduce a novel Focus on Focus (FoF) framework with paired pathology-genomic training and applicable pathology-only inference, enhancing molecular-pathology representation effectively. Specifically, we propose a Focus-oriented Representation Learning (FRL) module to encourage the model to identify regions positively or negatively related to glioma grading and guide it to focus on the diagnostic areas with a consistency constraint. To effectively link the molecular biomarkers to morphological features, we propose a Multi-view Cross-modal Alignment (MCA) module that projects histopathology representations into molecular subspaces, aligning morphological features with corresponding molecular biomarker status by supervised contrastive learning. Experiments on the TCGA GBMLGG dataset demonstrate that our FoF framework significantly improves the glioma grading. Remarkably, our FoF achieves superior performance using only histopathology slides compared to existing multimodal methods. The source code is available at https://github.com/peterlipan/FoF.