Abstract
Automated and accurate classification of Whole Slide Image (WSI) is of great significance for the early diagnosis and treatment of cancer, which can be realized by Multi-Instance Learning (MIL). However, the current MIL method easily suffers from over-fitting due to the weak supervision of slide-level labels. In addition, it is difficult to distinguish discriminative instances in a WSI bag in the absence of pixel-level annotations. To address these problems, we propose a novel Clustering-Based Multi-Instance Learning method (CBMIL) for WSI classification. The CBMIL constructs feature set from phenotypic clusters to augment data for training the aggregation network. Meanwhile, a contrastive learning task is incorporated into the CBMIL for multi-task learning, which helps to regularize the feature aggregation process. In addition, the centroid of each phenotypic cluster is updated by the model, and the weights of the WSI patches are calculated by their similarity to the phenotypic centroids to highlight the significant patches. Our method is evaluated on two public WSI datasets (CAMELYON16 and TCGA-Lung) for binary tumor and cancer sub-types classification and achieves better performance and great interpretability compared with the state-of-the-art methods. The code is available at: https://github.com/wwu98934/CBMIL.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Bejnordi, B.E., et al.: Diagnostic assessment of deep learning algorithms for detection of lymph node metastases in women with breast cancer. JAMA 318(22), 2199–2210 (2017)
Chen, T., Kornblith, S., Norouzi, M., Hinton, G.: A simple framework for contrastive learning of visual representations. In: International Conference on Machine Learning, pp. 1597–1607. PMLR (2020)
Chen, X., Fan, H., Girshick, R., He, K.: Improved baselines with momentum contrastive learning. arXiv preprint arXiv:2003.04297 (2020)
Chen, X., He, K.: Exploring simple Siamese representation learning. In: Proceedings of the IEEE/CVF Conference on Computer Vision and Pattern Recognition, pp. 15750–15758 (2021)
Cornish, T.C., Swapp, R.E., Kaplan, K.J.: Whole-slide imaging: routine pathologic diagnosis. Adv. Anat. Pathol. 19(3), 152–159 (2012)
Courtiol, P., Tramel, E.W., Sanselme, M., Wainrib, G.: Classification and disease localization in histopathology using only global labels: a weakly-supervised approach. arXiv preprint arXiv:1802.02212 (2018)
Dietterich, T.G., Lathrop, R.H., Lozano-Pérez, T.: Solving the multiple instance problem with axis-parallel rectangles. Artif. Intell. 89(1–2), 31–71 (1997)
Feng, J., Zhou, Z.H.: Deep MIML network. In: Proceedings of the AAAI Conference on Artificial Intelligence, vol. 31 (2017)
Grill, J.B., et al.: Bootstrap your own latent-a new approach to self-supervised learning. Adv. Neural. Inf. Process. Syst. 33, 21271–21284 (2020)
He, K., Fan, H., Wu, Y., Xie, S., Girshick, R.: Momentum contrast for unsupervised visual representation learning. In: Proceedings of the IEEE/CVF Conference on Computer Vision and Pattern Recognition, pp. 9729–9738 (2020)
He, K., Zhang, X., Ren, S., Sun, J.: Deep residual learning for image recognition. In: Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition, pp. 770–778 (2016)
Ilse, M., Tomczak, J., Welling, M.: Attention-based deep multiple instance learning. In: International Conference on Machine Learning, pp. 2127–2136. PMLR (2018)
Kanavati, F., et al.: Weakly-supervised learning for lung carcinoma classification using deep learning. Sci. Rep. 10(1), 1–11 (2020)
Kingma, D.P., Ba, J.: Adam: a method for stochastic optimization. arXiv preprint arXiv:1412.6980 (2014)
Lee, J., Lee, Y., Kim, J., Kosiorek, A., Choi, S., Teh, Y.W.: Set transformer: a framework for attention-based permutation-invariant neural networks. In: International Conference on Machine Learning, pp. 3744–3753. PMLR (2019)
Li, B., Li, Y., Eliceiri, K.W.: Dual-stream multiple instance learning network for whole slide image classification with self-supervised contrastive learning. In: Proceedings of the IEEE/CVF Conference on Computer Vision and Pattern Recognition, pp. 14318–14328 (2021)
Loshchilov, I., Hutter, F.: SGDR: stochastic gradient descent with warm restarts. arXiv preprint arXiv:1608.03983 (2016)
Lu, M.Y., Chen, R.J., Wang, J., Dillon, D., Mahmood, F.: Semi-supervised histology classification using deep multiple instance learning and contrastive predictive coding. arXiv preprint arXiv:1910.10825 (2019)
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. Nat. Biomed. Eng. 5(6), 555–570 (2021)
Maron, O., Lozano-Pérez, T.: A framework for multiple-instance learning. Adv. Neural Inf. Process. Syst. 10 (1997)
Mobadersany, P., et al.: Predicting cancer outcomes from histology and genomics using convolutional networks. Proc. Natl. Acad. Sci. 115(13), E2970–E2979 (2018)
Pantanowitz, L., et al.: Review of the current state of whole slide imaging in pathology. J. Pathol. Inform. 2(1), 36 (2011)
Shao, Z., et al.: TransMIL: transformer based correlated multiple instance learning for whole slide image classification. Adv. Neural. Inf. Process. Syst. 34, 2136–2147 (2021)
Srinidhi, C.L., Ciga, O., Martel, A.L.: Deep neural network models for computational histopathology: a survey. Med. Image Anal. 67, 101813 (2021)
Tomczak, K., Czerwińska, P., Wiznerowicz, M.: The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge. Wspolczesna Onkol. 2015(1A), A68–A77 (2014)
Verma, V., Luong, T., Kawaguchi, K., Pham, H., Le, Q.: Towards domain-agnostic contrastive learning. In: International Conference on Machine Learning, pp. 10530–10541. PMLR (2021)
Wang, X., Yan, Y., Tang, P., Bai, X., Liu, W.: Revisiting multiple instance neural networks. Pattern Recogn. 74, 15–24 (2018)
Yamashita, R., Long, J., Saleem, A., Rubin, D.L., Shen, J.: Deep learning predicts postsurgical recurrence of hepatocellular carcinoma from digital histopathologic images. Sci. Rep. 11(1), 1–14 (2021)
Yao, J., Zhu, X., Jonnagaddala, J., Hawkins, N., Huang, J.: Whole slide images based cancer survival prediction using attention guided deep multiple instance learning networks. Med. Image Anal. 65, 101789 (2020)
Zhang, H., Cisse, M., Dauphin, Y.N., Lopez-Paz, D.: mixup: beyond empirical risk minimization. arXiv preprint arXiv:1710.09412 (2017)
Zhu, X., Yao, J., Zhu, F., Huang, J.: WSISA: making survival prediction from whole slide histopathological images. In: Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition, pp. 7234–7242 (2017)
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this paper
Cite this paper
Wu, W., Zhu, Z., Magnier, B., Wang, L. (2022). Clustering-Based Multi-instance Learning Network for Whole Slide Image Classification. In: Qin, W., Zaki, N., Zhang, F., Wu, J., Yang, F. (eds) Computational Mathematics Modeling in Cancer Analysis. CMMCA 2022. Lecture Notes in Computer Science, vol 13574. Springer, Cham. https://doi.org/10.1007/978-3-031-17266-3_10
Download citation
DOI: https://doi.org/10.1007/978-3-031-17266-3_10
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-17265-6
Online ISBN: 978-3-031-17266-3
eBook Packages: Computer ScienceComputer Science (R0)