UniMod: Enhancing Multi-Modal Medical Diagnosis through Cross-Modality and Within-Modality Alignment

While multimodal data integrating diverse imaging and clinical tabular records is crucial for accurate medical diagnosis, the arbitrary absence of specific modalities is prevalent in clinical practice, severely degrading the performance of multimodal models. Existing methods either discard missing modalities, leading to information loss, or struggle to synthesize them without capturing complex inter-modal dependencies. To address these limitations, we propose a novel Context-driven Missing-Modality Learning (CMML) framework, which sequentially performs modality synthesis and semantic alignment to achieve robust diagnosis under arbitrary missing conditions. Specifically, we design a Cascade Residual Transformer-based Autoencoder (CRTA) that leverages learnable context tokens acting as dataset-level semantic prior to capture inter-modal dependencies and synthesize key missing representations. These representations are further enriched by modality-specific memory banks. To resolve the discrepancy between original available and synthesized representations, we transform the learned context tokens into instance-adaptive semantic references by infusing multimodal representations from the CRTA's outputs. This reference guides the alignment of heterogeneous modality representations into a unified space, where class-aware contrastive refinement is finally applied to explore discriminative diagnostic cues. Extensive evaluations on skin lesion (Derm7pt), ocular disease (ODIR), and meningioma (MEN) datasets demonstrate that CMML significantly outperforms state-of-the-art (SOTA) methods, yielding AVG AUC improvements of 1.26%, 0.97%, and 1.32%, respectively.

Multimodal clinical prediction faces three challenges: multiple foundation models (FMs) with complementary strengths per modality, pervasive missing modalities at training and test time, and sample-specific variation in modality contributions. We introduce MedMIX, a multimodal framework that combines intra-modality expert fusion, learned inter-modality fusion, and training-only large--small model collaboration for robust medical prediction under incomplete modalities. Within each modality, MedMIX aggregates complementary embeddings from multiple small expert models; across modalities, it performs learned fusion over available modalities; and during training, it leverages large teacher models to improve deployed representations without additional inference cost. Across three heterogeneous benchmarks (OpenI, MIMIC-IV-MM, and MMIST-ccRCC), MedMIX achieves consistently strong performance while remaining robust under controlled missing-modality perturbations, and further demonstrates sustained robustness under cross-cohort shift on MIMIC-III. These results highlight MedMIX as a practical framework that unifies within-modality expert collaboration, sample-specific cross-modality fusion, and efficient large--small model collaboration while remaining robust to incomplete modalities.

Medical diagnosis requires the effective synthesis of visual manifestations and clinical metadata. However, existing methods often treat metadata as isolated tags, failing to exploit the rich semantic knowledge embedded in clinical descriptions. We propose PRIMA (Pre-training with Risk-integrated Image-Metadata Alignment), a framework that integrates domain-specific knowledge into multi-modal representation learning. We first curate an expert corpus of risk--disease correlations via Retrieval-Augmented Generation (RAG) to refine Clinical ModernBERT, embedding diagnostic priors into the text encoder. To bridge the modality gap, we introduce a dual-encoder pre-training strategy utilizing DINOv3 and our refined Clinical ModernBERT, optimized by a suite of four complementary loss functions. These losses are designed to capture multi-granular semantic alignment and handle the ambiguity of clinical correlations through soft labels. Finally, we leverage Qwen3 to fuse these aligned features for precise disease classification. Extensive experiments demonstrate that PRIMA effectively harmonizes pixel-level features with abstract clinical expertise, consistently outperforming other state-of-the-art methods. Notably, our framework achieves strong performance without requiring massive data collection or exhaustive computational resources. Our code will is available at https://github.com/yqwang01/PRIMA.