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Unsupervised Learning-Based Nonrigid Registration of High Resolution Histology Images

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Machine Learning in Medical Imaging (MLMI 2020)

Abstract

The use of different dyes during histological sample preparation reveals distinct tissue properties and may improve the diagnosis. Nonetheless, the staining process deforms the tissue slides and registration is necessary before further processing. The importance of this problem led to organizing an open challenge named Automatic Non-rigid Histological Image Registration Challenge (ANHIR), organized jointly with the IEEE ISBI 2019 conference. The challenge organizers provided 481 image pairs and a server-side evaluation platform making it possible to reliably compare the proposed algorithms. The majority of the methods proposed for the challenge were based on the classical, iterative image registration, resulting in high computational load and arguable usefulness in clinical practice due to the long analysis time. In this work, we propose a deep learning-based unsupervised nonrigid registration method, that provides results comparable to the solutions of the best scoring teams, while being significantly faster during the inference. We propose a multi-level, patch-based training and inference scheme that makes it possible to register images of almost any size, up to the highest resolution provided by the challenge organizers. The median target registration error is close to 0.2% of the image diagonal while the average registration time, including the data loading and initial alignment, is below 3 s. We freely release both the training and inference code making the results fully reproducible.

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References

  1. Borovec, J., Munoz-Barrutia, A., Kybic, J.: Benchmarking of image registration methods for differently stained histological slides. In: IEEE International Conference on Image Processing, pp. 3368–3372 (2018)

    Google Scholar 

  2. Borovec, J., et al.: ANHIR: automatic non-rigid histological image registration challenge. IEEE Trans. Med. Imaging (2020)

    Google Scholar 

  3. Borovec, J., et al.: ANHIR Website. https://anhir.grand-challenge.org

  4. Fernandez-Gonzalez, R., et al.: System for combined three-dimensional morphological and molecular analysis of thick tissue specimens. Microsc. Res. Tech. 59(6), 522–530 (2002)

    Article  Google Scholar 

  5. Gupta, L., Klinkhammer, B., Boor, P., Merhof, D., Gadermayr, M.: Stain independent segmentation of whole slide images: a case study in renal histology. In: IEEE ISBI, pp. 1360–1364 (2018)

    Google Scholar 

  6. Mikhailov, I., Danilova, N., Malkov, P.: The immune microenvironment of various histological types of EBV-associated gastric cancer. Virchows Archiv (2018)

    Google Scholar 

  7. Bueno, G., Deniz, O.: AIDPATH: Academia and Industry Collaboration for Digital Pathology. http://aidpath.eu

  8. Lotz, J., Weiss, N., Heldmann, S.: Robust, fast and accurate: a 3-step method for automatic histological image registration. arXiv:1903.12063 (2019)

  9. Haber, E., Modersitzki, J.: Intensity gradient based registration and fusion of multi-modal images. In: Larsen, R., Nielsen, M., Sporring, J. (eds.) MICCAI 2006. LNCS, vol. 4191, pp. 726–733. Springer, Heidelberg (2006). https://doi.org/10.1007/11866763_89

    Chapter  Google Scholar 

  10. Venet, L., Pati, S., Yushkevich, P., Bakas, S.: Accurate and robust alignment of variable-stained histologic images using a general-purpose greedy diffeomorphic registration tool. arXiv:1904.11929 (2019)

  11. Joshi, S., Davis, B., Jomier, M., Gerig, G.: Unbiased diffeomorphic atlas construction for computational anatomy. NeuroImage 23, 151–160 (2004)

    Article  Google Scholar 

  12. Yushkevich, P., et al.: Fast automatic segmentation of hippocampal subfields and medial temporal lobe subregions in 3 Tesla and 7 Tesla T2-weighted MRI. Alzheimer’s Dementia 12, 126–127 (2016)

    Article  Google Scholar 

  13. Wodzinski, M., Skalski, A.: Automatic nonrigid histological image registration with adaptive multistep algorithm. arXiv:1904.00982 (2019)

  14. Heinrich, M., et al.: MIND: modality independent neighbourhood descriptor for multi-modal deformable registration. Med. Image Anal. 16(7), 1423–1435 (2012)

    Article  Google Scholar 

  15. Zhao, S., Lau, T., Luo, J., Chang, E., Xu, Y.: Unsupervised 3D end-to-end medical image registration with volume tweening network. IEEE J. Biomed. Health Inform. (2019). (Early Access)

    Google Scholar 

  16. de Vos, B., Berendsen, F., Viergever, M., Sokooti, H., Staring, M., Isgum, I.: A deep learning framework for unsupervised affine and deformable image registration. Med. Image Anal. 52, 128–143 (2019)

    Article  Google Scholar 

  17. Fan, J., Cao, X., Wang, Q., Yap, P., Shen, D.: Adversarial learning for mono- or multi-modal registration. Med. Image Anal. 58 (2019)

    Google Scholar 

  18. Wodzinski, M.: The Source Code. https://github.com/lNefarin/DeepHistReg

  19. Wodzinski, M., Müller, H.: Learning-based affine registration of histological images. In: Špiclin, Ž., McClelland, J., Kybic, J., Goksel, O. (eds.) WBIR 2020. LNCS, vol. 12120, pp. 12–22. Springer, Cham (2020). https://doi.org/10.1007/978-3-030-50120-4_2

    Chapter  Google Scholar 

  20. Ronneberger, O., Fischer, P., Brox, T.: U-Net: convolutional networks for biomedical image segmentation. In: Navab, N., Hornegger, J., Wells, W.M., Frangi, A.F. (eds.) MICCAI 2015. LNCS, vol. 9351, pp. 234–241. Springer, Cham (2015). https://doi.org/10.1007/978-3-319-24574-4_28

    Chapter  Google Scholar 

  21. Wu, Y., He, K.: Group normalization. arXiv:1803.084943 (2018)

  22. Fischer, B., Modersitzki, J.: Curvature based image registration. J. Math. Imaging Vis. 18(1), 81–85 (2003)

    Article  MathSciNet  Google Scholar 

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Acknowledgments

This work was funded by NCN Preludium project no. UMO-2018/29/N/ST6/00143 and NCN Etiuda project no. UMO-2019/32/T/ST6/00065.

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Correspondence to Marek Wodzinski .

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Wodzinski, M., Müller, H. (2020). Unsupervised Learning-Based Nonrigid Registration of High Resolution Histology Images. In: Liu, M., Yan, P., Lian, C., Cao, X. (eds) Machine Learning in Medical Imaging. MLMI 2020. Lecture Notes in Computer Science(), vol 12436. Springer, Cham. https://doi.org/10.1007/978-3-030-59861-7_49

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  • DOI: https://doi.org/10.1007/978-3-030-59861-7_49

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