# K-Stain: Keypoint-Driven Correspondence for H&E-to-IHC Virtual Staining

arXiv: https://arxiv.org/abs/2511.06709 · HTML: https://mlsanity.com/paper/2511.06709/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 30 of its 46 references that are in the map.
- First posted on arXiv 10 Nov 2025.

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

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [Very Deep Convolutional Networks for Large-Scale Image Recognition](https://mlsanity.com/paper/1409.1556/) (2014)
- [The Unreasonable Effectiveness of Deep Features as a Perceptual Metric](https://mlsanity.com/paper/1801.03924/) (2018)
- [Image-to-Image Translation with Conditional Adversarial Networks](https://mlsanity.com/paper/1611.07004/) (2016)
- [Perceptual Losses for Real-Time Style Transfer and Super-Resolution](https://mlsanity.com/paper/1603.08155/) (2016)
- [High-Resolution Image Synthesis and Semantic Manipulation with Conditional GANs](https://mlsanity.com/paper/1711.11585/) (2017)
- [Contrastive Learning for Unpaired Image-to-Image Translation](https://mlsanity.com/paper/2007.15651/) (2020)
- [SegMamba: Long-range Sequential Modeling Mamba For 3D Medical Image Segmentation](https://mlsanity.com/paper/2401.13560/) (2024)
- [Geometry-Consistent Generative Adversarial Networks for One-Sided Unsupervised Domain Mapping](https://mlsanity.com/paper/1809.05852/) (2018)
- [Breaking the Dilemma of Medical Image-to-image Translation](https://mlsanity.com/paper/2110.06465/) (2021)
- [StainGAN: Stain Style Transfer for Digital Histological Images](https://mlsanity.com/paper/1804.01601/) (2018)
- [BCI: Breast Cancer Immunohistochemical Image Generation through Pyramid Pix2pix](https://mlsanity.com/paper/2204.11425/) (2022)
- [Adaptive Supervised PatchNCE Loss for Learning H&E-to-IHC Stain Translation with Inconsistent Groundtruth Image Pairs](https://mlsanity.com/paper/2303.06193/) (2023)
- [NestedFormer: Nested Modality-Aware Transformer for Brain Tumor Segmentation](https://mlsanity.com/paper/2208.14876/) (2022)
- [Cross-conditioned Diffusion Model for Medical Image to Image Translation](https://mlsanity.com/paper/2409.08500/) (2024)
- [A Robust and Interpretable Deep Learning Framework for Multi-modal Registration via Keypoints](https://mlsanity.com/paper/2304.09941/) (2023)
- [Dual-Reference Source-Free Active Domain Adaptation for Nasopharyngeal Carcinoma Tumor Segmentation across Multiple Hospitals](https://mlsanity.com/paper/2309.13401/) (2023)
- [Pathological Semantics-Preserving Learning for H&E-to-IHC Virtual Staining](https://mlsanity.com/paper/2407.03655/) (2024)
- [Serp-Mamba: Advancing High-Resolution Retinal Vessel Segmentation with Selective State-Space Model](https://mlsanity.com/paper/2409.04356/) (2024)
- [Multi-scale Cell Instance Segmentation with Keypoint Graph based Bounding Boxes](https://mlsanity.com/paper/1907.09140/) (2019)
- [HybridMIM: A Hybrid Masked Image Modeling Framework for 3D Medical Image Segmentation](https://mlsanity.com/paper/2303.10333/) (2023)
- [Virtual histological staining of unlabeled autopsy tissue](https://mlsanity.com/paper/2308.00920/) (2023)
- [Virtual Histological Staining of Label-Free Total Absorption Photoacoustic Remote Sensing (TA-PARS)](https://mlsanity.com/paper/2203.02584/) (2022)
- [Structural Cycle GAN for Virtual Immunohistochemistry Staining of Gland Markers in the Colon](https://mlsanity.com/paper/2308.13182/) (2023)
- [Volumetric landmark detection with a multi-scale shift equivariant neural network](https://mlsanity.com/paper/2003.01639/) (2020)
- [Keypoint-Augmented Self-Supervised Learning for Medical Image Segmentation with Limited Annotation](https://mlsanity.com/paper/2310.01680/) (2023)
- [Gaussian kernel smoothing](https://mlsanity.com/paper/2007.09539/) (2020)
- [StainFuser: Controlling Diffusion for Faster Neural Style Transfer in Multi-Gigapixel Histology Images](https://mlsanity.com/paper/2403.09302/) (2024)
- [HistoStarGAN: A Unified Approach to Stain Normalisation, Stain Transfer and Stain Invariant Segmentation in Renal Histopathology](https://mlsanity.com/paper/2210.09798/) (2022)

## Abstract (arXiv)

Virtual staining offers a promising method for converting Hematoxylin and Eosin (H&E) images into Immunohistochemical (IHC) images, eliminating the need for costly chemical processes. However, existing methods often struggle to utilize spatial information effectively due to misalignment in tissue slices. To overcome this challenge, we leverage keypoints as robust indicators of spatial correspondence, enabling more precise alignment and integration of structural details in synthesized IHC images. We introduce K-Stain, a novel framework that employs keypoint-based spatial and semantic relationships to enhance synthesized IHC image fidelity. K-Stain comprises three main components: (1) a Hierarchical Spatial Keypoint Detector (HSKD) for identifying keypoints in stain images, (2) a Keypoint-aware Enhancement Generator (KEG) that integrates these keypoints during image generation, and (3) a Keypoint Guided Discriminator (KGD) that improves the discriminator's sensitivity to spatial details. Our approach leverages contextual information from adjacent slices, resulting in more accurate and visually consistent IHC images. Extensive experiments show that K-Stain outperforms state-of-the-art methods in quantitative metrics and visual quality.