Deep Instance-Level Hard Negative Mining Model for Histopathology Images

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 WSI 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.

[1]  Max Welling,et al.  Attention-based Deep Multiple Instance Learning , 2018, ICML.

[2]  Lin Wu,et al.  Deep adaptive feature embedding with local sample distributions for person re-identification , 2017, Pattern Recognit..

[3]  Nasir M. Rajpoot,et al.  Locality Sensitive Deep Learning for Detection and Classification of Nuclei in Routine Colon Cancer Histology Images , 2016, IEEE Trans. Medical Imaging.

[4]  Yan Xu,et al.  Deep learning of feature representation with multiple instance learning for medical image analysis , 2014, 2014 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP).

[5]  Joel H. Saltz,et al.  Patch-Based Convolutional Neural Network for Whole Slide Tissue Image Classification , 2015, 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[6]  J. S. Marron,et al.  Multiple Instance Learning for Heterogeneous Images: Training a CNN for Histopathology , 2018, MICCAI.

[7]  N. Otsu A threshold selection method from gray level histograms , 1979 .

[8]  Xue Li,et al.  Deep Attention-Based Spatially Recursive Networks for Fine-Grained Visual Recognition , 2019, IEEE Transactions on Cybernetics.

[9]  Ling Shao,et al.  Cycle-Consistent Deep Generative Hashing for Cross-Modal Retrieval , 2018, IEEE Transactions on Image Processing.

[10]  Melih Kandemir,et al.  Empowering Multiple Instance Histopathology Cancer Diagnosis by Cell Graphs , 2014, MICCAI.

[11]  Dayong Wang,et al.  Deep Learning for Identifying Metastatic Breast Cancer , 2016, ArXiv.

[12]  Bill Triggs,et al.  Histograms of oriented gradients for human detection , 2005, 2005 IEEE Computer Society Conference on Computer Vision and Pattern Recognition (CVPR'05).

[13]  Nico Karssemeijer,et al.  Deep learning-based assessment of tumor-associated stroma for diagnosing breast cancer in histopathology images , 2017, 2017 IEEE 14th International Symposium on Biomedical Imaging (ISBI 2017).

[14]  Tony X. Han,et al.  Multiple Instance Learning Convolutional Neural Networks for object recognition , 2016, 2016 23rd International Conference on Pattern Recognition (ICPR).

[15]  Andrei Popescu-Belis,et al.  Explaining the Stars: Weighted Multiple-Instance Learning for Aspect-Based Sentiment Analysis , 2014, EMNLP.

[16]  Yanjun Han,et al.  Avoiding False Positive in Multi-Instance Learning , 2010, NIPS.

[17]  Guoqing Liu,et al.  Key Instance Detection in Multi-Instance Learning , 2012, ACML.

[18]  Andrei Popescu-Belis,et al.  Explicit Document Modeling through Weighted Multiple-Instance Learning , 2017, J. Artif. Intell. Res..

[19]  Mei Chen,et al.  Low Dimensional Representation of Fisher Vectors for Microscopy Image Classification , 2017, IEEE Transactions on Medical Imaging.

[20]  Zhuowen Tu,et al.  Multiple clustered instance learning for histopathology cancer image classification, segmentation and clustering , 2012, 2012 IEEE Conference on Computer Vision and Pattern Recognition.

[21]  Brendan J. Frey,et al.  Classifying and segmenting microscopy images with deep multiple instance learning , 2015, Bioinform..

[22]  Lin Wu,et al.  Where-and-When to Look: Deep Siamese Attention Networks for Video-Based Person Re-Identification , 2018, IEEE Transactions on Multimedia.

[23]  Abhinav Gupta,et al.  Training Region-Based Object Detectors with Online Hard Example Mining , 2016, 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).