# Score-based Diffusion Model for Unpaired Virtual Histology Staining

arXiv: https://arxiv.org/abs/2506.23184 · HTML: https://mlsanity.com/paper/2506.23184/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Placed in Medical imaging and segmentation, one of 14 directions in Diffusion models.
- Builds on 16 of its 29 references that are in the map.
- First posted on arXiv 29 Jun 2025.

## Placed in

- Diffusion models / [Medical imaging and segmentation](https://mlsanity.com/diffusion/medical-imaging-and-segmentation/)

## Builds on (most cited first, 16 of 16)

- [Score-Based Generative Modeling through Stochastic Differential Equations](https://mlsanity.com/paper/2011.13456/) (2020)
- [SDEdit: Guided Image Synthesis and Editing with Stochastic Differential Equations](https://mlsanity.com/paper/2108.01073/) (2021)
- [Contrastive Learning for Unpaired Image-to-Image Translation](https://mlsanity.com/paper/2007.15651/) (2020)
- [ILVR: Conditioning Method for Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2108.02938/) (2021)
- [Dual Diffusion Implicit Bridges for Image-to-Image Translation](https://mlsanity.com/paper/2203.08382/) (2022)
- [EGSDE: Unpaired Image-to-Image Translation via Energy-Guided Stochastic Differential Equations](https://mlsanity.com/paper/2207.06635/) (2022)
- [StyleDiffusion: Controllable Disentangled Style Transfer via Diffusion Models](https://mlsanity.com/paper/2308.07863/) (2023)
- [Structure-Preserving Super Resolution with Gradient Guidance](https://mlsanity.com/paper/2003.13081/) (2020)
- [A Morphology Focused Diffusion Probabilistic Model for Synthesis of Histopathology Images](https://mlsanity.com/paper/2209.13167/) (2022)
- [BCI: Breast Cancer Immunohistochemical Image Generation through Pyramid Pix2pix](https://mlsanity.com/paper/2204.11425/) (2022)
- [DDM2: Self-Supervised Diffusion MRI Denoising with Generative Diffusion Models](https://mlsanity.com/paper/2302.03018/) (2023)
- [CycleNet: Rethinking Cycle Consistency in Text-Guided Diffusion for Image Manipulation](https://mlsanity.com/paper/2310.13165/) (2023)
- [Adaptive Supervised PatchNCE Loss for Learning H&E-to-IHC Stain Translation with Inconsistent Groundtruth Image Pairs](https://mlsanity.com/paper/2303.06193/) (2023)
- [Pathological Semantics-Preserving Learning for H&E-to-IHC Virtual Staining](https://mlsanity.com/paper/2407.03655/) (2024)
- [StainDiffuser: MultiTask Dual Diffusion Model for Virtual Staining](https://mlsanity.com/paper/2403.11340/) (2024)
- [Cross-modal Diffusion Modelling for Super-resolved Spatial Transcriptomics](https://mlsanity.com/paper/2404.12973/) (2024)

## Built on by (most cited first, 1 of 1)

- [HaDM-ST: Histology-Assisted Differential Modeling for Spatial Transcriptomics Generation](https://mlsanity.com/paper/2508.07225/) (2025)

## Abstract (arXiv)

Hematoxylin and eosin (H&E) staining visualizes histology but lacks specificity for diagnostic markers. Immunohistochemistry (IHC) staining provides protein-targeted staining but is restricted by tissue availability and antibody specificity. Virtual staining, i.e., computationally translating the H&E image to its IHC counterpart while preserving the tissue structure, is promising for efficient IHC generation. Existing virtual staining methods still face key challenges: 1) effective decomposition of staining style and tissue structure, 2) controllable staining process adaptable to diverse tissue and proteins, and 3) rigorous structural consistency modelling to handle the non-pixel-aligned nature of paired H&E and IHC images. This study proposes a mutual-information (MI)-guided score-based diffusion model for unpaired virtual staining. Specifically, we design 1) a global MI-guided energy function that disentangles the tissue structure and staining characteristics across modalities, 2) a novel timestep-customized reverse diffusion process for precise control of the staining intensity and structural reconstruction, and 3) a local MI-driven contrastive learning strategy to ensure the cellular level structural consistency between H&E-IHC images. Extensive experiments demonstrate the our superiority over state-of-the-art approaches, highlighting its biomedical potential. Codes will be open-sourced upon acceptance.