Skip to main content

RandStainNA: Learning Stain-Agnostic Features from Histology Slides by Bridging Stain Augmentation and Normalization

  • Conference paper
  • First Online:
Medical Image Computing and Computer Assisted Intervention – MICCAI 2022 (MICCAI 2022)

Abstract

Stain variations often decrease the generalization ability of deep learning based approaches in digital histopathology analysis. Two separate proposals, namely stain normalization (SN) and stain augmentation (SA), have been spotlighted to reduce the generalization error, where the former alleviates the stain shift across different medical centers using template image and the latter enriches the accessible stain styles by the simulation of more stain variations. However, their applications are bounded by the selection of template images and the construction of unrealistic styles. To address the problems, we unify SN and SA with a novel RandStainNA scheme, which constrains variable stain styles in a practicable range to train a stain agnostic deep learning model. The RandStainNA is applicable to stain normalization in a collection of color spaces i.e. HED, HSV, LAB. Additionally, we propose a random color space selection scheme to gain extra performance improvement. We evaluate our method by two diagnostic tasks i.e. tissue subtype classification and nuclei segmentation, with various network backbones. The performance superiority over both SA and SN yields that the proposed RandStainNA can consistently improve the generalization ability, that our models can cope with more incoming clinical datasets with unpredicted stain styles. The codes is available at https://github.com/yiqings/RandStainNA.

Y. Shen and Y. Luo—Equal contributions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Becht, E., et al.: Dimensionality reduction for visualizing single-cell data using umap. Nat. Biotechnol. 37(1), 38–44 (2019)

    Article  Google Scholar 

  2. Ciompi, F., et al.: The importance of stain normalization in colorectal tissue classification with convolutional networks. In: 2017 IEEE 14th International Symposium on Biomedical Imaging (ISBI 2017), pp. 160–163. IEEE (2017)

    Google Scholar 

  3. Dosovitskiy, A., et al.: An image is worth 16x16 words: Transformers for image recognition at scale. arXiv preprint arXiv:2010.11929 (2020)

  4. Gowda, S.N., Yuan, C.: ColorNet: Investigating the importance of color spaces for image classification. In: Jawahar, C.V., Li, H., Mori, G., Schindler, K. (eds.) ACCV 2018. LNCS, vol. 11364, pp. 581–596. Springer, Cham (2019). https://doi.org/10.1007/978-3-030-20870-7_36

    Chapter  Google Scholar 

  5. Gupta, V., Singh, A., Sharma, K., Bhavsar, A.: Automated classification for breast cancer histopathology images: Is stain normalization important? In: Cardoso, M.J., et al. (eds.) CARE/CLIP -2017. LNCS, vol. 10550, pp. 160–169. Springer, Cham (2017). https://doi.org/10.1007/978-3-319-67543-5_16

    Chapter  Google Scholar 

  6. Gurcan, M.N., et al.: Histopathological image analysis: A review. IEEE Rev. Biomed. Eng. 2, 147–171 (2009)

    Article  Google Scholar 

  7. He, K., et al.: Deep residual learning for image recognition. In: Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition, pp. 770–778 (2016)

    Google Scholar 

  8. Howard, A., et al.: Searching for mobilenetv3. In: Proceedings of the IEEE/CVF International Conference on Computer Vision, pp. 1314–1324 (2019)

    Google Scholar 

  9. Kather, J.N., et al.: Predicting survival from colorectal cancer histology slides using deep learning: A retrospective multicenter study. PLoS Med. 16(1), e1002730 (2019)

    Google Scholar 

  10. Ke, J., et al.: Style normalization in histology with federated learning. In: 2021 IEEE 18th International Symposium on Biomedical Imaging (ISBI), pp. 953–956. IEEE (2021)

    Google Scholar 

  11. Khan, A.M., et al.: A nonlinear mapping approach to stain normalization in digital histopathology images using image-specific color deconvolution. IEEE Trans. Biomed. Eng. 61(6), 1729–1738 (2014)

    Article  Google Scholar 

  12. Kumar, N., et al.: A multi-organ nucleus segmentation challenge. IEEE Trans. Med. Imaging 39(5), 1380–1391 (2019)

    Article  Google Scholar 

  13. Liu, Z., et al.: Swin transformer: Hierarchical vision transformer using shifted windows. In: Proceedings of the IEEE/CVF International Conference on Computer Vision, pp. 10012–10022 (2021)

    Google Scholar 

  14. Nadeem, S., Hollmann, T., Tannenbaum, A.: Multimarginal Wasserstein Barycenter for stain normalization and augmentation. In: Martel, A.L., et al. (eds.) MICCAI 2020. LNCS, vol. 12265, pp. 362–371. Springer, Cham (2020). https://doi.org/10.1007/978-3-030-59722-1_35

    Chapter  Google Scholar 

  15. Otsu, N.: A threshold selection method from gray-level histograms. IEEE Trans. Syst. Man Cybern. 9(1), 62–66 (1979)

    Article  Google Scholar 

  16. Reinhard, E., et al.: Color transfer between images. IEEE Comput. Graphics Appl. 21(5), 34–41 (2001)

    Article  Google Scholar 

  17. Salehi, P., et al.: Pix2pix-based stain-to-stain translation: a solution for robust stain normalization in histopathology images analysis. In: 2020 International Conference on Machine Vision and Image Processing (MVIP), pp. 1–7. IEEE (2020)

    Google Scholar 

  18. Shaban, M.T., et al.: Staingan: Stain style transfer for digital histological images. In: 2019 IEEE 16th International Symposium on Biomedical Imaging (Isbi 2019), pp. 953–956. IEEE (2019)

    Google Scholar 

  19. Tan, M., et al.: Efficientnet: Rethinking model scaling for convolutional neural networks. In: International Conference on Machine Learning, pp. 6105–6114. PMLR (2019)

    Google Scholar 

  20. Tellez, D., et al.: H and E stain augmentation improves generalization of convolutional networks for histopathological mitosis detection. In: Medical Imaging 2018: Digital Pathology, vol. 10581, p. 105810Z. International Society for Optics and Photonics (2018)

    Google Scholar 

  21. Tellez, D., et al.: Whole-slide mitosis detection in h &e breast histology using phh3 as a reference to train distilled stain-invariant convolutional networks. IEEE Trans. Med. Imaging 37(9), 2126–2136 (2018)

    Article  Google Scholar 

  22. Tellez, D., et al.: Quantifying the effects of data augmentation and stain color normalization in convolutional neural networks for computational pathology. Med. Image Anal. 58, 101544 (2019)

    Google Scholar 

  23. Wagner, S.J., et al.: Structure-preserving multi-domain stain color augmentation using style-transfer with disentangled representations. In: de Bruijne, M., et al. (eds.) MICCAI 2021. LNCS, vol. 12908, pp. 257–266. Springer, Cham (2021). https://doi.org/10.1007/978-3-030-87237-3_25

    Chapter  Google Scholar 

  24. Wang, Y.Y., et al.: A color-based approach for automated segmentation in tumor tissue classification. In: 2007 29th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, pp. 6576–6579. IEEE (2007)

    Google Scholar 

  25. Zanjani, F.G., et al.: Stain normalization of histopathology images using generative adversarial networks. In: 2018 IEEE 15th International symposium on biomedical imaging (ISBI 2018), pp. 573–577. IEEE (2018)

    Google Scholar 

  26. Zhou, Y., Onder, O.F., Dou, Q., Tsougenis, E., Chen, H., Heng, P.-A.: CIA-Net: robust nuclei instance segmentation with contour-aware information aggregation. In: Chung, A.C.S., Gee, J.C., Yushkevich, P.A., Bao, S. (eds.) IPMI 2019. LNCS, vol. 11492, pp. 682–693. Springer, Cham (2019). https://doi.org/10.1007/978-3-030-20351-1_53

    Chapter  Google Scholar 

Download references

Acknowledgements

This work has been supported by NSFC grants 62102247.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jing Ke .

Editor information

Editors and Affiliations

1 Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (pdf 4112 KB)

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this paper

Check for updates. Verify currency and authenticity via CrossMark

Cite this paper

Shen, Y., Luo, Y., Shen, D., Ke, J. (2022). RandStainNA: Learning Stain-Agnostic Features from Histology Slides by Bridging Stain Augmentation and Normalization. In: Wang, L., Dou, Q., Fletcher, P.T., Speidel, S., Li, S. (eds) Medical Image Computing and Computer Assisted Intervention – MICCAI 2022. MICCAI 2022. Lecture Notes in Computer Science, vol 13432. Springer, Cham. https://doi.org/10.1007/978-3-031-16434-7_21

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-16434-7_21

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-16433-0

  • Online ISBN: 978-3-031-16434-7

  • eBook Packages: Computer ScienceComputer Science (R0)

Publish with us

Policies and ethics