Mixture of Mini Experts: Overcoming the Linear Layer Bottleneck in Multiple Instance Learning

Multiple Instance Learning (MIL) is the dominant framework for gigapixel whole-slide image (WSI) classification in computational pathology. However, current MIL aggregators route all instances through a shared pathway, constraining their capacity to specialise across the pathological heterogeneity inherent in each slide. Mixture-of-Experts (MoE) methods offer a natural remedy by partitioning instances across specialised expert subnetworks; yet unconstrained softmax routing may yield highly imbalanced utilisation, where one or a few experts absorb most routing mass, collapsing the mixture back to a near-single-pathway solution. To address these limitations, we propose ROAM (Region-graph OptimAl-transport Mixture-of-experts), a spatially aware MoE-MIL aggregator that routes region tokens to expert poolers via capacity-constrained entropic optimal transport, promoting balanced expert utilisation by construction. ROAM operates on spatial region tokens, obtained by compressing dense patch bags into spatially binned units that align routing with local tissue neighbourhoods and introduces two key mechanisms: (i) region-to-expert assignment formulated as entropic optimal transport (Sinkhorn) with explicit per slide capacity marginals, enforcing balanced expert utilisation without auxiliary load-balancing losses; and (ii) graph-regularised Sinkhorn iterations that diffuse routing assignments over the spatial region graph, encouraging neighbouring regions to coherently route to the same experts. Evaluated on four WSI benchmarks with frozen foundation-model patch embeddings, ROAM achieves performance competitive against strong MIL and MoE baselines, and on NSCLC generalisation (TCGA-CPTAC) reaches external AUC 0.845 +- 0.019.

Multiple instance learning (MIL) has become the main paradigm for whole-slide image (WSI) analysis in computational pathology. However, existing MIL aggregators are still typically trained from scratch for each downstream task, relying on limited slide-level labels to learn both aggregation mechanisms and downstream discriminative representations simultaneously. As a result, they often suffer from unstable optimization, overfitting, and limited transferability. Similar to pretrained ResNet and Vision Transformer models in natural image learning, MIL also requires reusable pretrained initialization. However, high-quality slide-level pretraining data remain scarce, and MIL models are usually lightweight and weakly supervised, making large-scale pretraining difficult in practice. To address this challenge, we propose a distillation-based pretraining framework for MIL, which leverages two slide-level foundation models, TITAN and CARE, as teachers to transfer their representational knowledge into a diverse set of MIL architectures. To effectively balance supervision from different teachers, we further introduce an angular dispersion normalized distillation loss. The distilled weights are then used as initialization for downstream adaptation. We conduct systematic evaluations on 15 benchmark datasets under both linear probing and full-parameter fine-tuning, and further validate its advantages in few-shot scenarios. Experimental results show that pretraining generally improves MIL aggregators over from scratch training, especially in linear-probing and few-shot settings, while maintaining the computational efficiency of lightweight MIL models. Code is available at https://github.com/fu0201/MIL_Pretrained.

Multiple instance learning (MIL) has become a standard paradigm for whole slide image (WSI) analysis in digital pathology, as it enables slide-level prediction without dense annotations. Existing MIL methods typically rely on exhaustive extraction and encoding of high-resolution patches. However, this practice suffers from two critical limitations in real-world clinical settings: it struggles to capture global visual cues at lower magnifications, and incurs substantial computational overhead due to the massive number of high-resolution patches per slide. To address these limitations, we propose an efficient low-resolution multiple instance learning (LRMIL) framework that transfers high-resolution knowledge to low-resolution representations. LRMIL adopts a two-stage distillation strategy. First, patch-level cross-resolution distillation aligns low-resolution patch embeddings with high-resolution representations. Second, slide-level knowledge distillation trains a low-resolution student MIL model under both slide-level supervision and teacher guidance. At inference time, LRMIL operates exclusively on low-resolution patches, substantially reducing data preprocessing and computational cost. Extensive experiments on multiple WSI benchmarks demonstrate that LRMIL consistently outperforms state-of-the-art MIL methods while achieving more efficient inference. These results highlight LRMIL as a practical and scalable solution for WSI analysis in clinical pathology.