LEAF-Mamba: Feature Adaptation and Fusion for Whole Slide Image Analysis

Whole slide image analysis is commonly formulated as multiple instance learning (MIL), where instance features are contextually updated and aggregated into a slide representation, a process we term slide encoding dynamics. Recently, selective state-space models (SSM) have emerged as promising MIL architectures due to their long-sequence modeling capability and linear complexity. However, existing SSM-based MIL methods rely solely on visual features during MIL. Meanwhile, in large-scale WSIs, where sparse diagnostically decisive regions are surrounded by abundant irrelevant information, such purely vision-driven selective dynamics can misallocate state updates and readouts, causing the evolving SSM state to accumulate task-irrelevant evidence and dilute critical diagnostic cues over long scan trajectories. In this work, we propose the Knowledge-Aware Hidden-State Modulation architecture (KHiM-Mamba), which innovatively regulates Mamba's core selective state-space mechanism with explicit knowledge priors, steering slide encoding dynamics toward diagnostically meaningful evidence accumulation. Specifically, we redesign the original SSM layer to perform knowledge modulation operations during the evolution of hidden states, thereby guiding what visual evidence is accumulated and retrieved from the hidden state at each encoding step. Furthermore, we additionally introduce a local-adaptive vocabulary retrieval module that uses large language models to assign each patch fine-grained, tissue-specific semantic descriptions, enabling precise modulation across diverse tasks. Experiments on 11 public benchmarks across 4 tasks show that KHiM-Mamba consistently achieves state-of-the-art performance.

Whole Slide Image (WSI) analysis is pivotal in computational pathology, enabling cancer diagnosis by integrating morphological and architectural cues across magnifications. Multiple Instance Learning (MIL) serves as the standard framework for WSI analysis. Recently, Mamba has become a promising backbone for MIL, overtaking Transformers due to its efficiency and global context modeling capabilities originating from Natural Language Processing (NLP). However, existing Mamba-based MIL approaches face three critical challenges: (1) disruption of 2D spatial locality during 1D sequence flattening; (2) sub-optimal modeling of fine-grained local cellular structures; and (3) high memory peaks during inference on resource-constrained edge devices. Studies like MambaOut reveal that Mamba's SSM component is redundant for local feature extraction, where Gated CNNs suffice. Recognizing that WSI analysis demands both fine-grained local feature extraction akin to natural images, and global context modeling akin to NLP, we propose MambaBack, a novel hybrid architecture that harmonizes the strengths of Mamba and MambaOut. First, we propose the Hilbert sampling strategy to preserve the 2D spatial locality of tiles within 1D sequences, enhancing the model's spatial perception. Second, we design a hierarchical structure comprising a 1D Gated CNN block based on MambaOut to capture local cellular features, and a BiMamba2 block to aggregate global context, jointly enhancing multi-scale representation. Finally, we implement an asymmetric chunking design, allowing parallel processing during training and chunking-streaming accumulation during inference, minimizing peak memory usage for deployment. Experimental results on five datasets demonstrate that MambaBack outperforms seven state-of-the-art methods. Source code and datasets are publicly available.

Whole slide image (WSI) analysis heavily relies on multiple instance learning (MIL). While recent methods benefit from large-scale foundation models and advanced sequence modeling to capture long-range dependencies, they still struggle with two critical issues. First, directly applying frozen, task-agnostic features often leads to suboptimal separability due to the domain gap with specific histological tasks. Second, relying solely on global aggregators can cause over-smoothing, where sparse but critical diagnostic signals are overshadowed by the dominant background context. In this paper, we present ReconMIL, a novel framework designed to bridge this domain gap and balance global-local feature aggregation. Our approach introduces a Latent Space Reconstruction module that adaptively projects generic features into a compact, task-specific manifold, improving boundary delineation. To prevent information dilution, we develop a bi-stream architecture combining a Mamba-based global stream for contextual priors and a CNN-based local stream to preserve subtle morphological anomalies. A scale-adaptive selection mechanism dynamically fuses these two streams, determining when to rely on overall architecture versus local saliency. Evaluations across multiple diagnostic and survival prediction benchmarks show that ReconMIL consistently outperforms current state-of-the-art methods, effectively localizing fine-grained diagnostic regions while suppressing background noise. Visualization results confirm the models superior ability to localize diagnostic regions by effectively balancing global structure and local granularity.