ENGINEERING Information Technology & Electronic Engineering  2026 Vol.27 No.10 P.1-11

http://doi.org/10.1631/ENG.ITEE.2026.0118


High-fidelity unsupervised virtual staining for digital pathology via progressive Schrödinger bridge dynamics


Author(s):  Jianqiao YE, Jiahong SUN, Jiandong WANG, Xinyang LI, Puti YAN, Xingye CHEN

Affiliation(s):  1. National College for Excellent Engineers, Beihang University, Beijing 100191, China more

Corresponding email(s):   chenxingye@buaa.edu.cn

Key Words:  Virtual staining, Unsupervised learning, Schrödinger bridge, Digital pathology, Image processing


Jianqiao YE, Jiahong SUN, Jiandong WANG, Xinyang LI, Puti YAN, Xingye CHEN. High-fidelity unsupervised virtual staining for digital pathology via progressive Schrödinger bridge dynamics[J]. Journal of Zhejiang University Science C, 2026, 27(10): 1-11.

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author="Jianqiao YE, Jiahong SUN, Jiandong WANG, Xinyang LI, Puti YAN, Xingye CHEN",
journal="Journal of Zhejiang University Science C",
volume="27",
number="10",
pages="1-11",
year="2026",
publisher="Zhejiang University Press & Springer",
doi="10.1631/ENG.ITEE.2026.0118"
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%A Jiahong SUN
%A Jiandong WANG
%A Xinyang LI
%A Puti YAN
%A Xingye CHEN
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A1 - Jiandong WANG
A1 - Xinyang LI
A1 - Puti YAN
A1 - Xingye CHEN
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DOI - 10.1631/ENG.ITEE.2026.0118


Abstract: 
Virtual staining converts label-free autofluorescence (AF) images into hematoxylin and eosin (H&E)-like brightfield contrast for nondestructive pathology. We adapt the unpaired neural Schrödinger bridge (UNSB) framework to AF-to-H&E virtual staining and develop an enhanced UNSB (E-UNSB) model for pathology-oriented image translation. E-UNSB retains the unpaired, unidirectional, and progressive stochastic transport formulation of UNSB while introducing pathology-specific structural regularization to preserve cellular morphology and tissue architecture. In particular, saliency constraints and global feature consistency provide multi-scale structural guidance to reduce distortion during staining generation. Experiments demonstrate improved distributional similarity and morphometric consistency over the evaluated unsupervised baselines. Quantitative downstream analysis further indicates that virtual H&E images retain morphometric features relevant to pathological assessment, supporting their potential for high-throughput multimodal tissue analysis.

基于渐进薛定谔桥动力学的数字病理高保真无监督虚拟染色

叶剑桥1,2,孙嘉鸿3,王建东3,李欣阳4,阎菩提2,陈星晔2
1北京航空航天大学国家卓越工程师学院,中国北京市,100191
2北京航空航天大学电子信息工程学院,中国北京市,100191
3中国人民解放军总医院普通外科医学部,中国北京市,100853
4清华大学人工智能学院,中国北京市,100084
摘要:虚拟染色技术可将无标记自发荧光(AF)图像转化为类苏木精-伊红(H&E)明场对比度图像,实现无损病理检测。本研究将非配对神经薛定谔桥(UNSB)框架应用于自发荧光图像向H&E图像的虚拟染色任务,并构建面向病理图像转换的增强型UNSB(E-UNSB)模型。该框架继承了UNSB非配对、单向、渐进随机传输的建模形式,同时引入病理专属结构正则化约束,以保留细胞形态与组织结构。显著性约束和全局特征一致性提供了多尺度结构引导策略,以缓解染色图像生成过程中的失真。实验结果表明,相较于现有已评估的无监督基准方法,该模型在分布相似性和形态计量一致性方面均有提升。下游定量分析进一步证实,虚拟H&E图像能够保留病理评估所需的形态计量特征,可为高通量多模态组织分析提供支撑。

关键词:虚拟染色;无监督学习;薛定谔桥;数字病理;图像处理

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Reference

[1]Abraham T, Shaw A, O’Connor D, et al., 2020. Slide-free MUSE microscopy to H&E histology modality conversion via unpaired image-to-image translation GAN models. https://arxiv.org/abs/2008.08579

[2]Abraham T, Costa PC, Serafini CE, et al., 2023. Label- and slide-free tissue histology using 3D epi-mode quantitative phase imaging and virtual hematoxylin and eosin staining. Optica, 10(12):1605-1618.

[3]Anyi CL, You HZ, Li HK, et al., 2026. Label-free mapping of subcellular dynamics using wide-field interferometric scattering microscopy and spectral exponent analysis. PhotoniX Life, 1:11.

[4]Bai BJ, Wang HD, Li YZ, et al., 2022. Label-free virtual HER2 immunohistochemical staining of breast tissue using deep learning. BME Front, 2022:9786242.

[5]Bai BJ, Yang XL, Li YZ, et al., 2023. Deep learning-enabled virtual histological staining of biological samples. Light Sci Appl, 12(1):57.

[6]Bankhead P, Loughrey MB, Fernández JA, et al., 2017. QuPath: open source software for digital pathology image analysis. Sci Rep, 7(1):16878.

[7]Belaldavar C, Angadi PV, Mudenagudi U, 2024. QuPath for automated analysis of digital images of oral epithelial dysplasia. J Oral Maxillofac Pathol, 28(3):381-386.

[8]Bińkowski M, Sutherland DJ, Arbel M, et al., 2018. Demystifying MMD GANs. https://arxiv.org/abs/1801.01401

[9]Cao R, Nelson SD, Davis S, et al., 2023. Label-free intraoperative histology of bone tissue via deep-learning-assisted ultraviolet photoacoustic microscopy. Nat Biomed Eng, 7(2):124-134.

[10]de Haan K, Zhang YJ, Zuckerman JE, et al., 2021. Deep learning-based transformation of H&E stained tissues into special stains. Nat Commun, 12(1):4884.

[11]Feldman AT, Wolfe D, 2014. Tissue processing and hematoxylin and eosin staining. In: Day CE (Ed.), Histopathology: Methods in Molecular Biology. Humana Press, New York, p.31-43.

[12]Fu H, Gong MM, Wang CH, et al., 2019. Geometry-consistent generative adversarial networks for one-sided unsupervised domain mapping. Proc IEEE/CVF Conf on Computer Vision and Pattern Recognition, p.2422-2431.

[13]Guo XL, Tao YY, Zhang YZ, et al., 2026. CycleGAN-TMDE: an image dehazing model using cycle generative adversarial network with transmission map and depth estimation. Chin J Electron, 35(1):377-391.

[14]Heusel M, Ramsauer H, Unterthiner T, et al., 2017. GANs trained by a two time-scale update rule converge to a local Nash equilibrium. Proc 31st Int Conf on Neural Information Processing Systems, p.6629-6640.

[15]Huang JH, Kou TD, He TY, et al., 2025. Advances in deep learning-based virtual staining of pathological tissues. Laser Optoelectron Prog, 62(14):1400001 (in Chinese).

[16]Huang X, Liu MY, Belongie S, et al., 2018. Multimodal unsupervised image-to-image translation. Proc 15th European Conf on Computer Vision, p.179-196.

[17]Isola P, Zhu JY, Zhou TH, et al., 2017. Image-to-image translation with conditional adversarial networks. Proc IEEE Conf on Computer Vision and Pattern Recognition, p.5967-5976.

[18]Karkampouna S, Kruithof-de Julio M, 2023. Dataset EMPaCT TMA.

[19]Kim B, Kwon G, Kim K, et al., 2024. Unpaired image-to-image translation via neural Schrödinger bridge. Proc 12th Int Conf on Learning Representations.

[20]Kreiss L, Jiang SW, Li X, et al., 2023. Digital staining in optical microscopy using deep learning - a review. PhotoniX, 4(1):34.

[21]Li X, 2023. UTOM Dataset: Whole-Slide Pathological Images of Various Kinds of Cancers.

[22]Li XY, Zhang GX, Qiao H, et al., 2021. Unsupervised content-preserving transformation for optical microscopy. Light Sci Appl, 10(1):44.

[23]Liu ZJ, Chen LC, Cheng HX, et al., 2024. Virtual formalin-fixed and paraffin-embedded staining of fresh brain tissue via stimulated Raman CycleGAN model. Sci Adv, 10(13):eadn3426.

[24]Özbey M, Dalmaz O, Dar S, et al., 2023. Unsupervised medical image translation with adversarial diffusion models. IEEE Trans Med Imag, 42(12):3524-3539.

[25]Park T, Efros AA, Zhang R, et al., 2020. Contrastive learning for unpaired image-to-image translation. Proc 16th European Conf on Computer Vision, p.319-345.

[26]Pati P, Karkampouna S, Bonollo F, et al., 2024. Accelerating histopathology workflows with generative AI-based virtually multiplexed tumour profiling. Nat Mach Intell, 6(9):1077-1093.

[27]Qiu FH, Zhang YY, Guo XG, et al., 2024. Weakly supervised virtual immunohistochemistry staining via Schrödinger bridge method. Proc IEEE Int Conf on Bioinformatics and Biomedicine, p.2369-2375.

[28]Rivenson Y, Wang HD, Wei ZS, et al., 2019. Virtual histological staining of unlabelled tissue-autofluorescence images via deep learning. Nat Biomed Eng, 3(6):466-477.

[29]Sun JH, Ye JQ, Chen SY, et al., 2026. Artificial intelligence assisted multi-model pathological diagnosis of breast cancer based on multispectral autofluorescence images. npj Breast Cancer, 12(1):62.

[30]Wang JJ, Xiong B, Zhou Y, et al., 2025. VM-GAN: a value mapping framework for virtual staining of optical microscopy images. Opt Expr, 33(12):25641-25655.

[31]Wang Q, Fernandes S, Williams GOS, et al., 2022. Deep learning-assisted co-registration of full-spectral autofluorescence lifetime microscopic images with H&E-stained histology images. Commun Biol, 5(1):1119.

[32]Wang XY, Yang S, Zhang J, et al., 2022. Transformer-based unsupervised contrastive learning for histopathological image classification. Med Image Anal, 81:102559.

[33]Xie SA, Xu YW, Gong MM, et al., 2023. Unpaired image-to-image translation with shortest path regularization. Proc IEEE/CVF Conf on Computer Vision and Pattern Recognition, p.10177-10187.

[34]Yang XL, Bai BJ, Zhang YJ, et al., 2022. Virtual stain transfer in histology via cascaded deep neural networks. ACS Photon, 9(9):3134-3143.

[35]Ye JQ, Sun JH, 2025. Deep Learning Virtual Staining Dataset: Breast, Mouse, and Organoids.

[36]Zhang RR, E HH, Yuan LF, et al., 2024. FGM-SPCL: open-set recognition network for medical images based on fine-grained data mixture and spatial position constraint loss. Chin J Electron, 33(4):1023-1033.

[37]Zhang SW, Yang B, Yang HP, et al., 2024. Potential rapid intraoperative cancer diagnosis using dynamic full-field optical coherence tomography and deep learning: a prospective cohort study in breast cancer patients. Sci Bull, 69(11):1748-1756.

[38]Zhang YJ, Huang LZ, Pillar N, et al., 2025. Pixel super-resolved virtual staining of label-free tissue using diffusion models. Nat Commun, 16(1):5016.

[39]Zhu JY, Park T, Isola P, et al., 2017. Unpaired image-to-image translation using cycle-consistent adversarial networks. Proc IEEE Int Conf on Computer Vision, p.2242-2251.

Full Text:   <12>

Summary:  <12>

CLC number: TP391

On-line Access: 2026-11-11

Received: 2026-04-24

Revision Accepted: 2026-08-06

Crosschecked: 2026-11-11

Cited: 0

Clicked: 14

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Jianqiao YE

0009-0007-0187-5799

Xingye CHEN

0000-0001-9482-9319

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