RMDL: Recalibrated multi-instance deep learning for whole slide gastric image classification

The whole slide histopathology images (WSIs) play a critical role in gastric cancer diagnosis. However, due to the large scale of WSIs and various sizes of the abnormal area, how to select informative regions and analyze them are quite challenging during the automatic diagnosis process. The multi-instance learning based on the most discriminative instances can be of great benefit for whole slide gastric image diagnosis. In this paper, we design a recalibrated multi-instance deep learning method (RMDL) to address this challenging problem. We first select the discriminative instances, and then utilize these instances to diagnose diseases based on the proposed RMDL approach. The designed RMDL network is capable of capturing instance-wise dependencies and recalibrating instance features according to the importance coefficient learned from the fused features. Furthermore, we build a large whole-slide gastric histopathology image dataset with detailed pixel-level annotations. Experimental results on the constructed gastric dataset demonstrate the significant improvement on the accuracy of our proposed framework compared with other state-of-the-art multi-instance learning methods. Moreover, our method is general and can be extended to other diagnosis tasks of different cancer types based on WSIs.

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

[2]  Ghassan Hamarneh,et al.  Topology Aware Fully Convolutional Networks for Histology Gland Segmentation , 2016, MICCAI.

[3]  Geoffrey E. Hinton,et al.  Distilling the Knowledge in a Neural Network , 2015, ArXiv.

[4]  Hao Chen,et al.  SFCN-OPI: Detection and Fine-grained Classification of Nuclei Using Sibling FCN with Objectness Prior Interaction , 2017, AAAI.

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

[6]  Pheng-Ann Heng,et al.  Fast ScanNet: Fast and Dense Analysis of Multi-Gigapixel Whole-Slide Images for Cancer Metastasis Detection , 2019, IEEE Transactions on Medical Imaging.

[7]  Imari Sato,et al.  Semi-supervised Learning for Biomedical Image Segmentation via Forest Oriented Super Pixels(Voxels) , 2017, MICCAI.

[8]  Qitao Huang,et al.  Weakly Supervised Learning for Whole Slide Lung Cancer Image Classification , 2018 .

[9]  Dorit Merhof,et al.  Multi-class single-label classification of histopathological whole-slide images , 2016, 2016 IEEE 13th International Symposium on Biomedical Imaging (ISBI).

[10]  Bowen Zhou,et al.  A Structured Self-attentive Sentence Embedding , 2017, ICLR.

[11]  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.

[12]  U. Ladabaum,et al.  Risks and Predictors of Gastric Adenocarcinoma in Patients with Gastric Intestinal Metaplasia and Dysplasia: A Population-Based Study , 2016, The American Journal of Gastroenterology.

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

[14]  Ghassan Hamarneh,et al.  Predicting Cancer with a Recurrent Visual Attention Model for Histopathology Images , 2018, MICCAI.

[15]  Metin Nafi Gürcan,et al.  A Multiple Instance Learning Approach toward Optimal Classification of Pathology Slides , 2010, 2010 20th International Conference on Pattern Recognition.

[16]  Xin Wang,et al.  Cancer Metastasis Detection via Spatially Structured Deep Network , 2017, IPMI.

[17]  Xiaohui Xie,et al.  Deep Multi-instance Networks with Sparse Label Assignment for Whole Mammogram Classification , 2016, bioRxiv.

[18]  Luca Maria Gambardella,et al.  Assessment of algorithms for mitosis detection in breast cancer histopathology images , 2014, Medical Image Anal..

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

[20]  Enhua Wu,et al.  Squeeze-and-Excitation Networks , 2017, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[21]  Linda G. Shapiro,et al.  Multi-Instance Multi-Label Learning for Multi-Class Classification of Whole Slide Breast Histopathology Images , 2018, IEEE Transactions on Medical Imaging.

[22]  Dwarikanath Mahapatra,et al.  Semi-supervised Segmentation of Optic Cup in Retinal Fundus Images Using Variational Autoencoder , 2017, MICCAI.

[23]  Aleksey Boyko,et al.  Detecting Cancer Metastases on Gigapixel Pathology Images , 2017, ArXiv.

[24]  Hao Chen,et al.  ScanNet: A Fast and Dense Scanning Framework for Metastastic Breast Cancer Detection from Whole-Slide Image , 2017, 2018 IEEE Winter Conference on Applications of Computer Vision (WACV).

[25]  Yi Yang,et al.  Attention to Scale: Scale-Aware Semantic Image Segmentation , 2015, 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[26]  Jun Kong,et al.  Computer-aided prognosis of neuroblastoma on whole-slide images: Classification of stromal development , 2009, Pattern Recognit..

[27]  Dmitrii Bychkov,et al.  Deep learning based tissue analysis predicts outcome in colorectal cancer , 2018, Scientific Reports.

[28]  Junzhou Huang,et al.  WSISA: Making Survival Prediction from Whole Slide Histopathological Images , 2017, 2017 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[29]  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).

[30]  Juho Kannala,et al.  Deep learning for magnification independent breast cancer histopathology image classification , 2016, 2016 23rd International Conference on Pattern Recognition (ICPR).

[31]  Jianzhong Wu,et al.  Stacked Sparse Autoencoder (SSAE) for Nuclei Detection on Breast Cancer Histopathology Images , 2016, IEEE Transactions on Medical Imaging.

[32]  Karolina Sikorska,et al.  The prognostic and potentially predictive value of the Laurén classification in oesophageal adenocarcinoma. , 2017, European journal of cancer.

[33]  Xiaogang Wang,et al.  Residual Attention Network for Image Classification , 2017, 2017 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[34]  Andrew H. Beck,et al.  Diagnostic Assessment of Deep Learning Algorithms for Detection of Lymph Node Metastases in Women With Breast Cancer , 2017, JAMA.

[35]  Harri Valpola,et al.  Weight-averaged consistency targets improve semi-supervised deep learning results , 2017, ArXiv.

[36]  Alberto Carmona-Bayonas,et al.  Lauren subtypes of advanced gastric cancer influence survival and response to chemotherapy: real-world data from the AGAMENON National Cancer Registry , 2017, British Journal of Cancer.

[37]  Zhuowen Tu,et al.  Weakly supervised histopathology cancer image segmentation and classification , 2014, Medical Image Anal..

[38]  Lin Yang,et al.  An Automatic Learning-Based Framework for Robust Nucleus Segmentation , 2016, IEEE Transactions on Medical Imaging.

[39]  Zhipeng Jia,et al.  Large scale tissue histopathology image classification, segmentation, and visualization via deep convolutional activation features , 2017, BMC Bioinformatics.

[40]  Hao Chen,et al.  Mitosis Detection in Breast Cancer Histology Images via Deep Cascaded Networks , 2016, AAAI.

[41]  Guy Cazuguel,et al.  Multiple-Instance Learning for Medical Image and Video Analysis , 2017, IEEE Reviews in Biomedical Engineering.

[42]  Laura H. Tang,et al.  Molecular Classification of Gastric Cancer: A New Paradigm , 2011, Clinical Cancer Research.

[43]  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).

[44]  Hiroki Kuniyasu,et al.  Molecular diagnosis of gastric cancer: present and future , 2001, Gastric Cancer.

[45]  Yuxin Peng,et al.  The application of two-level attention models in deep convolutional neural network for fine-grained image classification , 2014, 2015 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[46]  Richard S. Zemel,et al.  End-to-End Instance Segmentation with Recurrent Attention , 2016, 2017 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[47]  Michael S. Bernstein,et al.  ImageNet Large Scale Visual Recognition Challenge , 2014, International Journal of Computer Vision.

[48]  Sergey Ioffe,et al.  Inception-v4, Inception-ResNet and the Impact of Residual Connections on Learning , 2016, AAAI.

[49]  Luca Maria Gambardella,et al.  Mitosis Detection in Breast Cancer Histology Images with Deep Neural Networks , 2013, MICCAI.

[50]  Wenyu Liu,et al.  Revisiting multiple instance neural networks , 2016, Pattern Recognit..

[51]  David A. McAllester,et al.  Object Detection with Discriminatively Trained Part Based Models , 2010, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[52]  Loïc Le Folgoc,et al.  Attention U-Net: Learning Where to Look for the Pancreas , 2018, ArXiv.

[53]  Hai Su,et al.  Beyond Classification: Structured Regression for Robust Cell Detection Using Convolutional Neural Network , 2015, MICCAI.

[54]  Alex Graves,et al.  Recurrent Models of Visual Attention , 2014, NIPS.

[55]  Hao Chen,et al.  Gland segmentation in colon histology images: The glas challenge contest , 2016, Medical Image Anal..

[56]  Nassir Navab,et al.  AggNet: Deep Learning From Crowds for Mitosis Detection in Breast Cancer Histology Images , 2016, IEEE Trans. Medical Imaging.

[57]  Thomas Hofmann,et al.  Support Vector Machines for Multiple-Instance Learning , 2002, NIPS.

[58]  Stephen J. McKenna,et al.  Multiple Instance Cancer Detection by Boosting Regularised Trees , 2015, MICCAI.

[59]  Ben Glocker,et al.  Semi-supervised Learning for Network-Based Cardiac MR Image Segmentation , 2017, MICCAI.

[60]  Chi-Wing Fu,et al.  Uncertainty-aware Self-ensembling Model for Semi-supervised 3D Left Atrium Segmentation , 2019, MICCAI.

[61]  Jason Weston,et al.  Deep learning via semi-supervised embedding , 2008, ICML '08.

[62]  Jimmy Ba,et al.  Adam: A Method for Stochastic Optimization , 2014, ICLR.

[63]  Junzhou Huang,et al.  Subtype Cell Detection with an Accelerated Deep Convolution Neural Network , 2016, MICCAI.

[64]  Eric W. Tramel,et al.  Classification and Disease Localization in Histopathology Using Only Global Labels: A Weakly-Supervised Approach , 2018, ArXiv.

[65]  Philip H. S. Torr,et al.  Learn To Pay Attention , 2018, ICLR.

[66]  Shaoqun Zeng,et al.  From Detection of Individual Metastases to Classification of Lymph Node Status at the Patient Level: The CAMELYON17 Challenge , 2019, IEEE Transactions on Medical Imaging.

[67]  Xin Qi,et al.  Adversarial Domain Adaptation for Classification of Prostate Histopathology Whole-Slide Images , 2018, MICCAI.

[68]  Philip S. Yu,et al.  Private Model Compression via Knowledge Distillation , 2018, AAAI.

[69]  Hao Chen,et al.  MILD‐Net: Minimal information loss dilated network for gland instance segmentation in colon histology images , 2018, Medical Image Anal..