Enhui Chai

Sicheng Chen, Chad Wong, Tianyi Zhang et al.

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.

Enhui Chai, Sicheng Chen, Tianyi Zhang et al.

Pathological diagnosis is highly reliant on image analysis, where Regions of Interest (ROIs) serve as the primary basis for diagnostic evidence, while whole-slide image (WSI)-level tasks primarily capture aggregated patterns. To extract these critical morphological features, ROI-level Foundation Models (FMs) based on Vision Transformers (ViTs) and large-scale self-supervised learning (SSL) have been widely adopted. However, three core limitations remain in their application to ROI analysis: (1) cross-magnification domain shift, as fixed-scale pretraining hinders adaptation to diverse clinical settings; (2) inadequate local-global relationship modeling, wherein the ViT backbone of FMs suffers from high computational overhead and imprecise local characterization; (3) insufficient fine-grained sensitivity, as traditional self-attention mechanisms tend to overlook subtle diagnostic cues. To address these challenges, we propose SSMamba, a hybrid SSL framework that enables effective fine-grained feature learning without relying on large external datasets. This framework incorporates three domain-adaptive components: Mamba Masked Image Modeling (MAMIM) for mitigating domain shift, a Directional Multi-scale (DMS) module for balanced local-global modeling, and a Local Perception Residual (LPR) module for enhanced fine-grained sensitivity. Employing a two-stage pipeline, SSL pretraining on target ROI datasets followed by supervised fine-tuning (SFT), SSMamba outperforms 11 state-of-the-art (SOTA) pathological FMs on 10 public ROI datasets and surpasses 8 SOTA methods on 6 public WSI datasets. These results validate the superiority of task-specific architectural designs for pathological image analysis.

Enhui Chai, Sicheng Chen, Tianyi Zhang et al.

Accurate analysis of histopathological images is critical for disease diagnosis and treatment planning. Whole-slide images (WSIs), which digitize tissue specimens at gigapixel resolution, are fundamental to this process but require aggregating thousands of patches for slide-level predictions. Multiple Instance Learning (MIL) tackles this challenge with a two-stage paradigm, decoupling tile-level embedding and slide-level prediction. However, most existing methods implicitly embed patch representations in homogeneous Euclidean spaces, overlooking the hierarchical organization and regional heterogeneity of pathological tissues. This limits current models' ability to capture global tissue architecture and fine-grained cellular morphology. To address this limitation, we introduce a hybrid hyperbolic-Euclidean representation that embeds WSI features in dual geometric spaces, enabling complementary modeling of hierarchical tissue structures and local morphological details. Building on this formulation, we develop BatMIL, a WSI classification framework that leverages both geometric spaces. To model long-range dependencies among thousands of patches, we employ a structured state space sequence model (S4) backbone that encodes patch sequences with linear computational complexity. Furthermore, to account for regional heterogeneity, we introduce a chunk-level mixture-of-experts (MoE) module that groups patches into regions and dynamically routes them to specialized subnetworks, improving representational capacity while reducing redundant computation. Extensive experiments on seven WSI datasets spanning six cancer types demonstrate that BatMIL consistently outperforms state-of-the-art MIL approaches in slide-level classification tasks. These results indicate that geometry-aware representation learning offers a promising direction for next-generation computational pathology.