Spatial transcriptomics (ST) enables the simultaneous profiling of gene expression and tissue morphology, creating an opportunity to learn multimodal representations capturing shared morpho-transcriptomic structure. However, standard multimodal models often compress modalities into a common latent space without explicitly separating shared and modality-specific sources of variation, which may limit downstream utility. We investigate whether explicit disentanglement of shared and private latent components improves multimodal representation learning for paired Hematoxylin \& Eosin (H\&E) and ST data. We compare VAE-based and contrastive approaches, each in standard and disentangled variants, across two cancer cohorts under matched experimental conditions. Representations are evaluated using cross-modal reconstruction, downstream probing and cross-modal probe transfer. The experiments suggest two main trends. First, contrastive objectives yield higher downstream probing performance than VAE-based models. Second, disentangled variants improve the selected reconstruction and probing metrics, although the gains depend on the model family, task, direction, and disentanglement strength. Overall, our results suggest that explicitly factorizing shared and modality-specific information can improve multimodal representation learning for spatial transcriptomics and provides a useful evaluation framework for future foundation models.
Chuankai Xu, Cristiane De Carvalho Singulane, Mohammad Abuannadi +10cs.CV cs.MM
Multi-view cardiac magnetic resonance (CMR) imaging provides complementary anatomical information and is widely used for noninvasive disease assessment. Recent transformer-based models have demonstrated strong representation learning capabilities for CMR analysis; however, they typically learn unified latent embeddings that entangle view-specific anatomical variations with disease-related features. Such entanglement biases classifiers toward structural attributes rather than view-invariant pathological patterns. This issue is exacerbated in low-data regimes, particularly for underrepresented cardiac conditions, where limited samples increase the susceptibility to shortcut learning and view-dependent decision boundaries. To address this, we propose a Motion-Guided View--Disease Disentanglement framework MoViD built upon a ViT-MAE backbone. The model explicitly factorizes latent representations into view-specific and disease-discriminative components using dual-branch supervised contrastive objectives and a gradient-reversal adversarial constraint that minimizes disease leakage into the view embedding. Additionally, an annotation-free temporal motion feature, derived from inter-frame difference maps, is introduced to localize the beating heart region and suppress background artifacts. A focal reweighting mechanism is incorporated into the contrastive loss to mitigate class imbalance. We evaluate the framework on a private clinical venous thrombosis dataset and two public benchmarks (M&Ms, M&Ms2). Across disease classification and cardiac segmentation tasks, our approach consistently outperforms standard transformer baselines and demonstrates competitive performance against large-scale pretrained foundation models, validating the efficacy of structural disentanglement in medical image analysis.