Abstract
In computational pathology, deep learning (DL) models for tasks such as segmentation or tissue classification are known to suffer from domain shifts due to different staining techniques. Stain adaptation aims to reduce the generalization error between different stains by training a model on source stains that generalizes to target stains. Despite the abundance of target stain data, a key challenge is the lack of annotations. To address this, we propose a joint training between artificially labeled and unlabeled data including all available stained images called Unsupervised Latent Stain Adaptation (ULSA). Our method uses stain translation to enrich labeled source images with synthetic target images in order to increase the supervised signals. Moreover, we leverage unlabeled target stain images using stain-invariant feature consistency learning. With ULSA we present a semi-supervised strategy for efficient stain adaptation without access to annotated target stain data. Remarkably, ULSA is task agnostic in patch-level analysis for whole slide images (WSIs). Through extensive evaluation on external datasets, we demonstrate that ULSA achieves state-of-the-art (SOTA) performance in kidney tissue segmentation and breast cancer classification across a spectrum of staining variations. Our findings suggest that ULSA is an important framework for stain adaptation in computational pathology.
D. Reisenbüchler and L. Luttner—These authors contributed equally to this work.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Barisoni, L., Nast, C.C., Jennette, J.C., Hodgin, J.B., Herzenberg, A.M., Lemley, K.V., Conway, C.M., Kopp, J.B., Kretzler, M., Lienczewski, C., Avila-Casado, C., Bagnasco, S., Sethi, S., Tomaszewski, J., Gasim, A.H., Hewitt, S.M.: Digital pathology evaluation in the multicenter nephrotic syndrome study network (neptune). Clinical Journal of the American Society of Nephrology 8(8), 1449-1459 (2013). https://doi.org/10.2215/cjn.08370812, http://dx.doi.org/10.2215/CJN.08370812
Bouteldja, N., Hölscher, D.L., Klinkhammer, B.M., Buelow, R.D., Lotz, J., Weiss, N., Daniel, C., Amann, K., Boor, P.: Stain-independent deep learning-based analysis of digital kidney histopathology. The American Journal of Pathology 193(1), 73-83 (2023).https://doi.org/10.1016/j.ajpath.2022.09.011, http://dx.doi.org/10.1016/j.ajpath.2022.09.011
Bouteldja, N., Klinkhammer, B.M., Bülow, R.D., Droste, P., Otten, S.W., Freifrau von Stillfried, S., Moellmann, J., Sheehan, S.M., Korstanje, R., Menzel, S., Bankhead, P., Mietsch, M., Drummer, C., Lehrke, M., Kramann, R., Floege, J., Boor, P., Merhof, D.: Deep learning-based segmentation and quantification in experimental kidney histopathology. Journal of the American Society of Nephrology 32(1), 52-68 (Nov 2020).https://doi.org/10.1681/asn.2020050597, http://dx.doi.org/10.1681/ASN.2020050597
Howard, A., Lawrence, A., Sims, B., Tinsley, E., Kazmierczak, J., Borner, K., Godwin, L., Novaes, M., Culliton, P., Holland, R., Watson, R., Ju, Y.: Hubmap - hacking the kidney (2020), https://kaggle.com/competitions/hubmap-kidney-segmentation
Jiang, Y., Sui, X., Ding, Y., Xiao, W., Zheng, Y., Zhang, Y.: A semi-supervised learning approach with consistency regularization for tumor histopathological images analysis. Frontiers in Oncology 12 (Jan 2023).https://doi.org/10.3389/fonc.2022.1044026, http://dx.doi.org/10.3389/fonc.2022.1044026
Kidney Precision Medicine Project: Kidney Precision Medicine Project Data. Accessed September 01, 2023. https://www.kpmp.org, the results here are in whole or part based upon data generated by the Kidney Precision Medicine Project. Funded by the National Institute of Diabetes and Digestive and Kidney Diseases
Lampert, T., Merveille, O., Schmitz, J., Forestier, G., Feuerhake, F., Wemmert, C.: Strategies for training stain invariant cnns. In: 2019 IEEE 16th International Symposium on Biomedical Imaging (ISBI 2019). IEEE (Apr 2019).https://doi.org/10.1109/isbi.2019.8759266, http://dx.doi.org/10.1109/ISBI.2019.8759266
Lu, M.Y., Williamson, D.F., Chen, T.Y., Chen, R.J., Barbieri, M., Mahmood, F.: Data-efficient and weakly supervised computational pathology on whole-slide images. Nature Biomedical Engineering 5(6), 555–570 (2021)
Macenko, M., Niethammer, M., Marron, J.S., Borland, D., Woosley, J.T., Guan, X., Schmitt, C., Thomas, N.E.: A method for normalizing histology slides for quantitative analysis. In: 2009 IEEE International Symposium on Biomedical Imaging: From Nano to Macro. IEEE (Jun 2009).https://doi.org/10.1109/isbi.2009.5193250, http://dx.doi.org/10.1109/ISBI.2009.5193250
Miyato, T., Maeda, S.i., Koyama, M., Ishii, S.: Virtual adversarial training: a regularization method for supervised and semi-supervised learning. IEEE transactions on pattern analysis and machine intelligence 41(8), 1979–1993 (2018)
Moor, M., Banerjee, O., Abad, Z.S.H., Krumholz, H.M., Leskovec, J., Topol, E.J., Rajpurkar, P.: Foundation models for generalist medical artificial intelligence. Nature 616(7956), 259-265 (2023).https://doi.org/10.1038/s41586-023-05881-4, http://dx.doi.org/10.1038/s41586-023-05881-4
Reinhard, E., Adhikhmin, M., Gooch, B., Shirley, P.: Color transfer between images. IEEE Computer graphics and applications 21(5), 34–41 (2001)
Reisenbüchler, D., Wagner, S.J., Boxberg, M., Peng, T.: Local attention graph-based transformer for multi-target genetic alteration prediction. In: Lecture Notes in Computer Science, pp. 377–386. Springer Nature Switzerland (2022)
Sohn, K., Berthelot, D., Li, C.L., Zhang, Z., Carlini, N., Cubuk, E.D., Kurakin, A., Zhang, H., Raffel, C.: Fixmatch: Simplifying semi-supervised learning with consistency and confidence (2020)
Wagner, S.J., Khalili, N., Sharma, R., Boxberg, M., Marr, C., de Back, W., Peng, T.: Structure-preserving multi-domain stain color augmentation using style-transfer with disentangled representations. In: Medical Image Computing and Computer Assisted Intervention - MICCAI 2021 (2021)
Wagner, S.J., Reisenbüchler, D., West, N.P., Niehues, J.M., Zhu, J., Foersch, S., Veldhuizen, G.P., Quirke, P., Grabsch, H.I., van den Brandt, P.A., Hutchins, G.G., Richman, S.D., Yuan, T., Langer, R., Jenniskens, J.C., Offermans, K., Mueller, W., Gray, R., Gruber, S.B., Greenson, J.K., Rennert, G., Bonner, J.D., Schmolze, D., Jonnagaddala, J., Hawkins, N.J., Ward, R.L., Morton, D., Seymour, M., Magill, L., Nowak, M., Hay, J., Koelzer, V.H., Church, D.N., Matek, C., Geppert, C., Peng, C., Zhi, C., Ouyang, X., James, J.A., Loughrey, M.B., Salto-Tellez, M., Brenner, H., Hoffmeister, M., Truhn, D., Schnabel, J.A., Boxberg, M., Peng, T., Kather, J.N., Church, D., Domingo, E., Edwards, J., Glimelius, B., Gogenur, I., Harkin, A., Hay, J., Iveson, T., Jaeger, E., Kelly, C., Kerr, R., Maka, N., Morgan, H., Oien, K., Orange, C., Palles, C., Roxburgh, C., Sansom, O., Saunders, M., Tomlinson, I.: Transformer-based biomarker prediction from colorectal cancer histology: A large-scale multicentric study. Cancer Cell 41(9), 1650–1661.e4 (Sep 2023https://doi.org/10.1016/j.ccell.2023.08.002, http://dx.doi.org/10.1016/j.ccell.2023.08.002
Wang, X., Du, Y., Yang, S., Zhang, J., Wang, M., Zhang, J., Yang, W., Huang, J., Han, X.: Retccl: Clustering-guided contrastive learning for whole-slide image retrieval. Medical Image Analysis 83, 102645 (2023).https://doi.org/10.1016/j.media.2022.102645, http://dx.doi.org/10.1016/j.media.2022.102645
Xie, Q., Dai, Z., Hovy, E., Luong, M.T., Le, Q.V.: Unsupervised data augmentation for consistency training (2020)
Zhu, J.Y., Park, T., Isola, P., Efros, A.A.: Unpaired image-to-image translation using cycle-consistent adversarial networks. In: 2017 IEEE International Conference on Computer Vision (ICCV). pp. 2242–2251 (2017).https://doi.org/10.1109/ICCV.2017.244
Zingman, I., Frayle, S., Tankoyeu, I., Sukhanov, S., Heinemann, F.: A comparative evaluation of image-to-image translation methods for stain transfer in histopathology (2023)
Acknowledgements
This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaf, DFG) under project number 445703531 and the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) under project numbers 01IS21067A and 01IS21067B. The authors gratefully acknowledge the computational and data resources provided by the Leibniz Supercomputing Centre (www.lrz.de).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Ethics declarations
Disclosure of Interests
The authors declare that they have no conflicts of interest related to this work.
1 Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
Copyright information
© 2024 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this paper
Cite this paper
Reisenbüchler, D., Luttner, L., Schaadt, N.S., Feuerhake, F., Merhof, D. (2024). Unsupervised Latent Stain Adaptation for Computational Pathology. In: Linguraru, M.G., et al. Medical Image Computing and Computer Assisted Intervention – MICCAI 2024. MICCAI 2024. Lecture Notes in Computer Science, vol 15011. Springer, Cham. https://doi.org/10.1007/978-3-031-72120-5_70
Download citation
DOI: https://doi.org/10.1007/978-3-031-72120-5_70
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-72119-9
Online ISBN: 978-3-031-72120-5
eBook Packages: Computer ScienceComputer Science (R0)