# SSMamba: A Self-Supervised Hybrid State Space Model for Pathological Image Classification

arXiv: https://arxiv.org/abs/2604.15711 · HTML: https://mlsanity.com/paper/2604.15711/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 32 of its 64 references that are in the map.
- First posted on arXiv 17 Apr 2026.

## Builds on (most cited first, 30 of 32)

- [An Image is Worth 16x16 Words: Transformers for Image Recognition at Scale](https://mlsanity.com/paper/2010.11929/) (2020)
- [Swin Transformer: Hierarchical Vision Transformer using Shifted Windows](https://mlsanity.com/paper/2103.14030/) (2021)
- [Masked Autoencoders Are Scalable Vision Learners](https://mlsanity.com/paper/2111.06377/) (2021)
- [Mamba: Linear-Time Sequence Modeling with Selective State Spaces](https://mlsanity.com/paper/2312.00752/) (2023)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [VMamba: Visual State Space Model](https://mlsanity.com/paper/2401.10166/) (2024)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [Self-supervised Visual Feature Learning with Deep Neural Networks: A Survey](https://mlsanity.com/paper/1902.06162/) (2019)
- [Contrastive Learning of Medical Visual Representations from Paired Images and Text](https://mlsanity.com/paper/2010.00747/) (2020)
- [Combining Recurrent, Convolutional, and Continuous-time Models with Linear State-Space Layers](https://mlsanity.com/paper/2110.13985/) (2021)
- [Dual-stream Multiple Instance Learning Network for Whole Slide Image Classification with Self-supervised Contrastive Learning](https://mlsanity.com/paper/2011.08939/) (2020)
- [Transfusion: Understanding Transfer Learning for Medical Imaging](https://mlsanity.com/paper/1902.07208/) (2019)
- [Big Self-Supervised Models Advance Medical Image Classification](https://mlsanity.com/paper/2101.05224/) (2021)
- [CMT: Convolutional Neural Networks Meet Vision Transformers](https://mlsanity.com/paper/2107.06263/) (2021)
- [Gland Segmentation in Colon Histology Images: The GlaS Challenge Contest](https://mlsanity.com/paper/1603.00275/) (2016)
- [Deep neural network models for computational histopathology: A survey](https://mlsanity.com/paper/1912.12378/) (2019)
- [Virchow2: Scaling Self-Supervised Mixed Magnification Models in Pathology](https://mlsanity.com/paper/2408.00738/) (2024)
- [MambaOut: Do We Really Need Mamba for Vision?](https://mlsanity.com/paper/2405.07992/) (2024)
- [On Translation Invariance in CNNs: Convolutional Layers can Exploit Absolute Spatial Location](https://mlsanity.com/paper/2003.07064/) (2020)
- [Visual Language Pretrained Multiple Instance Zero-Shot Transfer for Histopathology Images](https://mlsanity.com/paper/2306.07831/) (2023)
- [MambaMIL: Enhancing Long Sequence Modeling with Sequence Reordering in Computational Pathology](https://mlsanity.com/paper/2403.06800/) (2024)
- [Self Pre-training with Masked Autoencoders for Medical Image Classification and Segmentation](https://mlsanity.com/paper/2203.05573/) (2022)
- [A Petri Dish for Histopathology Image Analysis](https://mlsanity.com/paper/2101.12355/) (2021)
- [PathAsst: A Generative Foundation AI Assistant Towards Artificial General Intelligence of Pathology](https://mlsanity.com/paper/2305.15072/) (2023)
- [Weakly supervised multiple instance learning histopathological tumor segmentation](https://mlsanity.com/paper/2004.05024/) (2020)
- [Structured State Space Models for Multiple Instance Learning in Digital Pathology](https://mlsanity.com/paper/2306.15789/) (2023)
- [Distilling foundation models for robust and efficient models in digital pathology](https://mlsanity.com/paper/2501.16239/) (2025)
- [Instance-based Vision Transformer for Subtyping of Papillary Renal Cell Carcinoma in Histopathological Image](https://mlsanity.com/paper/2106.12265/) (2021)
- [ScoreNet: Learning Non-Uniform Attention and Augmentation for Transformer-Based Histopathological Image Classification](https://mlsanity.com/paper/2202.07570/) (2022)
- [MCUa: Multi-level Context and Uncertainty aware Dynamic Deep Ensemble for Breast Cancer Histology Image Classification](https://mlsanity.com/paper/2108.10709/) (2021)

## Abstract (arXiv)

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.