Multimodal clinical learning is increasingly important for integrating diverse patient data, including imaging, text, and personalised health records. However, it faces two fundamental challenges: i) modality missingness, where arbitrary subsets of modalities are unavailable at a given patient visit, ii) longitudinal dynamics, where the diagnostic significance of an observation depends on the patient's evolving disease trajectory over time. Existing methods address these challenges in isolation: missing-modality frameworks treat each visit as an independent static snapshot and discard temporal context, while longitudinal models often assume complete modality availability and degrade under systematic modality incompleteness. We propose LongMoE (Longitudinal Mixture-of-Experts), the unified framework to jointly address both challenges. LongMoE combines a context-aware imputation module with an attentional tokenization module that captures frequency-domain temporal patterns across irregular visit sequences, a trajectory-aware encoder for modeling disease progression, and context-conditioned Sparse MoE routing for patient-specific expert selection. Experiments on ADNI, OASIS-3, and MIMIC-IV show that LongMoE improves robustness under missing or weak contemporaneous modalities and remains competitive in full-modality settings, establishing a strong foundation for longitudinally-aware multimodal clinical learning.
An active challenge in developing multimodal machine learning (ML) models for healthcare is handling missing modalities during training and deployment. As clinical datasets are inherently temporal and sparse in terms of modality presence, capturing the underlying predictive signal via diagnostic multimodal ML models while retaining model explainability remains an ongoing challenge. In this work, we address this by re-framing clinical diagnosis as an autoregressive sequence modeling task, utilizing causal decoders from large language models (LLMs) to model a patient's multimodal trajectory. We first introduce a missingness-aware contrastive pre-training objective that integrates multiple modalities in datasets with missingness in a shared latent space. We then show that autoregressive sequence modeling with transformer-based architectures outperforms baselines on the MIMIC-IV and eICU fine-tuning benchmarks. Finally, we use interpretability techniques to move beyond performance boosts and find that across various patient stays, removing modalities leads to divergent behavior that our contrastive pre-training mitigates. By abstracting clinical diagnosis as sequence modeling and interpreting patient stay trajectories, we develop a framework to profile and handle missing modalities while addressing the canonical desideratum of safe, transparent clinical AI.
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.
Missing modalities are prevalent in real-world Alzheimer's disease (AD) assessment and pose a significant challenge to multimodal learning, particularly when the distribution of observed modality subsets differs between training and deployment. Such missingness pattern mismatch induces a conditional representation shift across modality subsets. Existing approaches that rely on implicit imputation or modality synthesis often fail to explicitly model modality availability and uncertainty, leading to overconfident dependence on synthesized features, reduced robustness, and miscalibrated uncertainty estimates. To address these limitations, we propose PRA-PoE, an incomplete multimodal learning framework that is equipped with Prototype-anchored Representation Alignment (PRA) and an Uncertainty-aware Product of Experts (UA-PoE) fusion mechanism. First, PRA uses learnable global prototypes and availability-conditioned tokens to encode modality availability, distinguish observed from missing modalities, re-synthesize features for missing modalities, and adaptively refine observed representations to align latent spaces across modality subsets, with the goal of reducing representation shift under varying missingness patterns. Second, UA-PoE models each modality as a Gaussian expert and performs closed-form Product of Experts fusion, where experts with higher uncertainty are automatically down-weighted via lower precision, improving uncertainty reliability. We evaluate PRA-PoE under a clinically realistic protocol by training with naturally missing data and testing on all non-empty modality combinations. PRA-PoE consistently outperforms the state-of-the-art across datasets, achieving a 5.4% relative improvement in average accuracy on ADNI and a 10.9% relative gain in average F1 on OASIS-3 over the strongest baseline across all non-empty modality subsets.