# KHiM-Mamba: Injecting Pathology Knowledge into Mamba via Hidden-State Modulation for Whole Slide Image Analysis

arXiv: https://arxiv.org/abs/2608.14757 · HTML: https://mlsanity.com/paper/2608.14757/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Mamba for medical image analysis, one of 10 directions in State-space sequence models (S4, Mamba).
- Builds on 18 of its 31 references that are in the map.
- First posted on arXiv 14 Aug 2026.

## Placed in

- State-space sequence models (S4, Mamba) / [Mamba for medical image analysis](https://mlsanity.com/ssm/mamba-for-medical-image-analysis/)

## Builds on (most cited first, 18 of 18)

- [LLaMA: Open and Efficient Foundation Language Models](https://mlsanity.com/paper/2302.13971/) (2023)
- [Qwen3 Technical Report](https://mlsanity.com/paper/2505.09388/) (2025)
- [Efficiently Modeling Long Sequences with Structured State Spaces](https://mlsanity.com/paper/2111.00396/) (2021)
- [Learning to Prompt for Vision-Language Models](https://mlsanity.com/paper/2109.01134/) (2021)
- [Transformers are SSMs: Generalized Models and Efficient Algorithms Through Structured State Space Duality](https://mlsanity.com/paper/2405.21060/) (2024)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [Vision Mamba: Efficient Visual Representation Learning with Bidirectional State Space Model](https://mlsanity.com/paper/2401.09417/) (2024)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [TransMIL: Transformer based Correlated Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2106.00908/) (2021)
- [Dual-stream Multiple Instance Learning Network for Whole Slide Image Classification with Self-supervised Contrastive Learning](https://mlsanity.com/paper/2011.08939/) (2020)
- [BRACS: A Dataset for BReAst Carcinoma Subtyping in H&E Histology Images](https://mlsanity.com/paper/2111.04740/) (2021)
- [Whole Slide Images are 2D Point Clouds: Context-Aware Survival Prediction using Patch-based Graph Convolutional Networks](https://mlsanity.com/paper/2107.13048/) (2021)
- [Interventional Bag Multi-Instance Learning On Whole-Slide Pathological Images](https://mlsanity.com/paper/2303.06873/) (2023)
- [MambaMIL: Enhancing Long Sequence Modeling with Sequence Reordering in Computational Pathology](https://mlsanity.com/paper/2403.06800/) (2024)
- [Structured State Space Models for Multiple Instance Learning in Digital Pathology](https://mlsanity.com/paper/2306.15789/) (2023)
- [Interpretable Vision-Language Survival Analysis with Ordinal Inductive Bias for Computational Pathology](https://mlsanity.com/paper/2409.09369/) (2024)
- [Multiple Instance Learning Framework with Masked Hard Instance Mining for Gigapixel Histopathology Image Analysis](https://mlsanity.com/paper/2509.11526/) (2025)
- [MambaMIL+: Modeling Long-Term Contextual Patterns for Gigapixel Whole Slide Image](https://mlsanity.com/paper/2512.17726/) (2025)

## Abstract (arXiv)

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.