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Deep Instance-Level Hard Negative Mining Model for Histopathology Images

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Medical Image Computing and Computer Assisted Intervention – MICCAI 2019 (MICCAI 2019)

Part of the book series: Lecture Notes in Computer Science ((LNIP,volume 11764))

Abstract

Histopathology image analysis can be considered as a Multiple instance learning (MIL) problem, where the whole slide histopathology image (WSI) is regarded as a bag of instances (i.e., patches) and the task is to predict a single class label to the WSI. However, in many real-life applications such as computational pathology, discovering the key instances that trigger the bag label is of great interest because it provides reasons for the decision made by the system. In this paper, we propose a deep convolutional neural network (CNN) model that addresses the primary task of a bag classification on a histopathology image and also learns to identify the response of each instance to provide interpretable results to the final prediction. We incorporate the attention mechanism into the proposed model to operate the transformation of instances and learn attention weights to allow us to find key patches. To perform a balanced training, we introduce adaptive weighing in each training bag to explicitly adjust the weight distribution in order to concentrate more on the contribution of hard samples. Based on the learned attention weights, we further develop a solution to boost the classification performance by generating the bags with hard negative instances. We conduct extensive experiments on colon and breast cancer histopathology data and show that our framework achieves state-of-the-art performance.

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References

  1. Bejnordi, B.E., et al.: Deep learning-based assessment of tumor-associated stroma for diagnosing breast cancer in histopathology images. In: ISBI (2017)

    Google Scholar 

  2. Couture, H.D., Marron, J.S., Perou, C.M., Troester, M.A., Niethammer, M.: Multiple instance learning for heterogeneous images: training a CNN for histopathology. In: Frangi, A.F., Schnabel, J.A., Davatzikos, C., Alberola-López, C., Fichtinger, G. (eds.) MICCAI 2018. LNCS, vol. 11071, pp. 254–262. Springer, Cham (2018). https://doi.org/10.1007/978-3-030-00934-2_29

    Chapter  Google Scholar 

  3. Dalal, N., Triggs, B.: Histograms of oriented gradients for human detection. In: CVPR (2005)

    Google Scholar 

  4. Han, Y., et al.: Avoiding false positive in multi-instance learning. In: NIPS (2010)

    Google Scholar 

  5. Hou, L., et al.: Patch-based convolutional neural network for whole slide tissue image classification. In: CVPR (2016)

    Google Scholar 

  6. Ilse, M., Tomczak, J., Welling, M.: Attention-based deep multiple instance learning. In: ICML (2018)

    Google Scholar 

  7. Kandemir, M., Zhang, C., Hamprecht, F.A.: Empowering multiple instance histopathology cancer diagnosis by cell graphs. In: Golland, P., Hata, N., Barillot, C., Hornegger, J., Howe, R. (eds.) MICCAI 2014. LNCS, vol. 8674, pp. 228–235. Springer, Cham (2014). https://doi.org/10.1007/978-3-319-10470-6_29

    Chapter  Google Scholar 

  8. Wu, L., Wang, Y., Gao, J., Li, X.: Where-and-when to look: deep Siamese attention networks for video-based person re-identification. IEEE Trans. Multimed. (2019)

    Google Scholar 

  9. Lin, W., Wang, Y., Li, X., Gao, J.: Deep attention-based spatially recursive networks for fine-grained visual recognition. IEEE Trans. Cybern. 49(5), 1791–1802 (2019)

    Article  Google Scholar 

  10. Kraus, O.Z., Ba, J.L., Frey, B.J.: Classifying and segmenting microscopy images with deep multiple instance learning. In: Bioinformatics (2016)

    Google Scholar 

  11. Liu, G., Wu, J., Zhou, Z.-H.: Key instance detection in multi-instance learning. In: ACML (2012)

    Google Scholar 

  12. Otsu, N.: A threshold selection method from gray-level histograms. In: SMCS (1979)

    Google Scholar 

  13. Pappas, N., Popescu-Belis, A.: Explaining the stars: weighted multiple-instance learning for aspect-based sentiment analysis. In: EMNLP (2014)

    Google Scholar 

  14. Pappas, N., Popescu-Belis, A.: Explicit document modeling through weighted multiple-instance learning. In: JAIR (2017)

    Google Scholar 

  15. Shrivastava, A., Gupta, A., Girshick, R.: Training region-based object detectors with online hard example mining. In: CVPR (2016)

    Google Scholar 

  16. Sirinukunwattana, K., et al.: Locality sensitive deep learning for detection and classification of nuclei in routine colon cancer histology images. In: T-MI (2016)

    Google Scholar 

  17. Song, Y., Li, Q., Huang, H., Feng, D., Chen, M., Cai, W.: Low dimensional representation of fisher vectors for microscopy image classification. In: T-MI (2017)

    Google Scholar 

  18. Sun, M., Han, T.X., Liu, M.C., Khodayari-Rostamabad, A.: Multiple instance learning convolutional neural networks for object recognition. In: ICPR (2016)

    Google Scholar 

  19. Wang, D., et al.: Deep learning for identifying metastatic breast cancer. arXiv preprint arXiv:1606.05718 (2016)

  20. Xu, Y., et al.: Multiple clustered instance learning for histopathology cancer image classification, segmentation and clustering. In: CVPR, June 2012

    Google Scholar 

  21. Xu, Y., et al.: Deep learning of feature representation with multiple instance learning for medical image analysis. In: ICASSP (2014)

    Google Scholar 

  22. Wu, L., Wang, Y., Gao, J., Li, X.: Deep adaptive feature embedding with local sample distributions for person re-identification. Pattern Recogn. 73, 275–288 (2018)

    Article  Google Scholar 

  23. Lin, W., Wang, Y., Li, X., Gao, J.: Deep attention-based spatially recursive networks for fine-grained visual recognition. IEEE Trans. Cybern. 49(5), 1791–1802 (2019)

    Article  Google Scholar 

  24. Wu, L., Wang, Y., Shao, L.: Cycle-consistent deep generative hashing for cross-modal retrieval. IEEE Trans. Image Process. (2019)

    Google Scholar 

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Acknowledgement

This research was funded by the Australian Government through the Australian Research Council and Sullivan Nicolaides Pathology under Linkage Project LP160101797.

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Correspondence to Lin Wu .

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Li, M., Wu, L., Wiliem, A., Zhao, K., Zhang, T., Lovell, B. (2019). Deep Instance-Level Hard Negative Mining Model for Histopathology Images. In: Shen, D., et al. Medical Image Computing and Computer Assisted Intervention – MICCAI 2019. MICCAI 2019. Lecture Notes in Computer Science(), vol 11764. Springer, Cham. https://doi.org/10.1007/978-3-030-32239-7_57

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  • DOI: https://doi.org/10.1007/978-3-030-32239-7_57

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  • Online ISBN: 978-3-030-32239-7

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