PANDA - Prototype-Anchored Alignment for Partially Unpaired Multimodal Learning, with Applications to Alzheimers MRI and TCGA Pathology

Abstract

Multimodal medical prediction often faces incomplete pairing: auxiliary modalities with complementary signal are available for only a subset of subjects (or none) and cannot be assumed at deployment. We introduce PANDA (Prototype Anchored Data Alignment), a two-stage framework that transfers auxiliary information to a primary-modality model without auxiliary inputs at inference. Stage 1 learns a shared embedding from the paired subset and estimates class prototypes from auxiliary modalities; Stage 2 trains the primary encoder on all subjects using cross-entropy plus alignment to the frozen prototypes. Because supervision is defined at the class-prototype level, PANDA accommodates arbitrary pairing rates, including zero subject overlap. We evaluate PANDA on two applications. On a 1,021-subject multi-scanner ADNI cohort, we perform AD/CN classification with three auxiliary modalities at distinct pairing rates: tabular scores (44.8%), FDG-PET (18.7%), and external handwriting kinematics (0% overlap). Relative to the same-backbone MRI-only baseline, PANDA attains AUC 0.868 +-0.020 (+7.9pp) and reduces 1.5T CN false positives by 24.3pp; on a fully trainable Conv5-FC3 backbone it reaches AUC 0.893 (best overall). A pairing-rate ablation shows that the joint anchor remains within seed noise from 75% to 5% pairing. On TCGA-Lung survival prediction from whole-slide images with RNA-seq as auxiliary data, PANDA improves over WSI-only on 2-year OS (AUC +3.5pp) and Cox PH (C-index +9.0pts) and outperforms full-fusion training, which underperforms WSI-only, while requiring no RNA at inference; wide confidence intervals on this smaller cohort keep the gains below conventional significance. Overall, PANDA provides a deployment-oriented mechanism for leveraging incomplete auxiliary modalities to improve primary-modality prediction.