Multimodal Fusion Methods for Whole-Slide Images and Clinical Data in Inflammatory Bowel Disease

The rapid digitization of histopathology slides has opened new opportunities for computational tools in clinical and research workflows. Content-based slide retrieval can help pathologists identify morphologically and semantically related precedent cases, supporting expert diagnosis and example-based education. Effective retrieval of whole-slide images (WSIs), however, remains challenging because gigapixel slides contain abundant irrelevant content, focal diagnostic patterns and slide-level semantic information that must be represented at a practicable search cost. Here we present PathSearch, a retrieval framework that combines fine-grained attentive mosaics with slide-level embeddings aligned through vision-language contrastive learning. Trained on 6,926 slide-report pairs, PathSearch captures both fine-grained morphological cues and high-level semantic patterns to enable accurate and flexible retrieval. The framework supports two key functionalities: (1) mosaic-based image-to-image (I2I) retrieval, ensuring accurate and efficient slide search; and (2) multimodal retrieval, where text queries can directly retrieve relevant slides. PathSearch was evaluated on eight tasks comprising 5,021 evaluation slides, spanning malignancy assessment on frozen and hematoxylin and eosin (H&E)-stained slides, lymph-node metastasis detection, tumor subtyping, mixed-gallery rare-cancer retrieval, and hepatocellular carcinoma (HCC) risk stratification. Internal and external experimental results demonstrate that PathSearch consistently outperforms the strongest existing methods without compromising multimodal accuracy. A multi-center reader study further demonstrated increases in task-level mean diagnostic accuracy, confidence, and inter-observer agreement with PathSearch's support. Together, these results support the effectiveness of PathSearch across diverse retrieval tasks and evaluation settings.

Pathology foundation models (FMs) have become central to computational histopathology, offering strong transfer performance across a wide range of diagnostic and prognostic tasks. The rapid proliferation of pathology foundation models creates a model-selection bottleneck: no single model is uniformly best, yet exhaustively adapting and validating many candidates for each downstream endpoint is prohibitively expensive. We address this challenge with a lightweight and novel model fusion strategy, LogitProd, which treats independently trained FM-based predictors as fixed experts and learns sample-adaptive fusion weights over their slide-level outputs. The fusion operates purely on logits, requiring no encoder retraining and no feature-space alignment across heterogeneous backbones. We further provide a theoretical analysis showing that the optimal weighted product fusion is guaranteed to perform at least as well as the best individual expert under the training objective. We systematically evaluate LogitProd on 22 benchmarks spanning WSI-level classification, tile-level classification, gene mutation prediction, and discrete-time survival modeling. LogitProd ranks first on 20/22 tasks and improves the average performance across all tasks by ~3% over the strongest single expert. LogitProd enables practitioners to upgrade heterogeneous FM-based pipelines in a plug-and-play manner, achieving multi-expert gains with $\sim$12$\times$ lower training cost than feature-fusion alternatives.

Whole slide imaging (WSI) has transformed digital pathology by enabling computational analysis of gigapixel histopathology images. Recent foundation model advances have accelerated progress in computational pathology, facilitating joint reasoning across pathology images, clinical reports, and structured data. Despite this progress, challenges remain: the extreme resolution of WSIs creates computational hurdles for visual learning; limited expert annotations constrain supervised approaches; integrating multimodal information while preserving biological interpretability remains difficult; and the opacity of modeling ultra-long visual sequences hinders clinical transparency. This review comprehensively surveys recent advances in multimodal computational pathology. We systematically analyze four research directions: (1) self-supervised representation learning and structure-aware token compression for WSIs; (2) multimodal data generation and augmentation; (3) parameter-efficient adaptation and reasoning-enhanced few-shot learning; and (4) multi-agent collaborative reasoning for trustworthy diagnosis. We specifically examine how token compression enables cross-scale modeling and how multi-agent mechanisms simulate a pathologist's "Chain of Thought" across magnifications to achieve uncertainty-aware evidence fusion. Finally, we discuss open challenges and argue that future progress depends on unified multimodal frameworks integrating high-resolution visual data with clinical and biomedical knowledge to support interpretable and safe AI-assisted diagnosis.