Efficient Multiple Instance Convolutional Neural Networks for Gigapixel Resolution Image Classification

Convolutional Neural Networks (CNNs) are state-of-theart models for many image and video classification tasks. However, training on large-size training samples is currently computationally impossible. Hence when the training data is multi-gigapixel images, only small patches of the original images can be used as training input. Since there is no guarantee that each patch is discriminative, we advocate the use of Multiple Instance Learning (MIL) to combine evidence from multiple patches sampled from the same image. In this paper we propose a framework that integrates MIL with CNNs. In our algorithm, patches of the images or videos are treated as instances, where only the imageor video-level label is given. Our algorithm iteratively identifies discriminative patches in a high resolution image and trains a CNN on them. In the test phase, instead of using voting to the predict the label of the image, we train a logistic regression model to aggregate the patch-level predictions. Our method selects discriminative patches more robustly through the use of Gaussian smoothing. We apply our method to glioma (the most common brain cancer) subtype classification based on multi-gigapixel whole slide images (WSI) from The Cancer Genome Atlas (TCGA) dataset. We can classify Glioblastoma (GBM) and Low-Grade Glioma (LGG) with an accuracy of 97%. Furthermore, for the first time, we attempt to classify the three most common subtypes of LGG, a much more challenging task. We achieved an accuracy of 57.1% which is similar to the inter-observer agreement between experienced pathologists.

[1]  Zhi-Hua Zhou,et al.  Neural Networks for Multi-Instance Learning , 2002 .

[2]  Bernhard Pfahringer,et al.  A Two-Level Learning Method for Generalized Multi-instance Problems , 2003, ECML.

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

[4]  Fernando De la Torre,et al.  Gaussian Processes Multiple Instance Learning , 2010, ICML.

[5]  Jun Kong,et al.  Integrated morphologic analysis for the identification and characterization of disease subtypes , 2012, J. Am. Medical Informatics Assoc..

[6]  A. Ruifrok,et al.  Quantification of histochemical staining by color deconvolution. , 2001, Analytical and quantitative cytology and histology.

[7]  Cenk Sokmensuer,et al.  Color Graphs for Automated Cancer Diagnosis and Grading , 2010, IEEE Transactions on Biomedical Engineering.

[8]  Bahram Parvin,et al.  Classification of Histology Sections via Multispectral Convolutional Sparse Coding , 2014, 2014 IEEE Conference on Computer Vision and Pattern Recognition.

[9]  D. Brat,et al.  Clarifying the diffuse gliomas: an update on the morphologic features and markers that discriminate oligodendroglioma from astrocytoma. , 2005, American journal of clinical pathology.

[10]  Qi Zhang,et al.  EM-DD: An Improved Multiple-Instance Learning Technique , 2001, NIPS.

[11]  David H. Wolpert,et al.  Stacked generalization , 1992, Neural Networks.

[12]  Vishal Monga,et al.  Automated discrimination of lower and higher grade gliomas based on histopathological image analysis , 2015, Journal of pathology informatics.

[13]  Chih-Jen Lin,et al.  LIBSVM: A library for support vector machines , 2011, TIST.

[14]  James R. Foulds,et al.  A review of multi-instance learning assumptions , 2010, The Knowledge Engineering Review.

[15]  George Papandreou,et al.  Weakly- and Semi-Supervised Learning of a DCNN for Semantic Image Segmentation , 2015, ArXiv.

[16]  Jan Ramon,et al.  Multi instance neural networks , 2000, ICML 2000.

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

[18]  Ivan Laptev,et al.  Weakly supervised object recognition with convolutional neural networks , 2014 .

[19]  Fabio A. González,et al.  Automatic detection of invasive ductal carcinoma in whole slide images with convolutional neural networks , 2014, Medical Imaging.

[20]  Matti Pietikäinen,et al.  Multiresolution Gray-Scale and Rotation Invariant Texture Classification with Local Binary Patterns , 2002, IEEE Trans. Pattern Anal. Mach. Intell..

[21]  Thomas G. Dietterich,et al.  Solving the Multiple Instance Problem with Axis-Parallel Rectangles , 1997, Artif. Intell..

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

[23]  Zheru Chi,et al.  Multi-instance multi-label image classification: A neural approach , 2013, Neurocomputing.

[24]  Pascal Vincent,et al.  Representation Learning: A Review and New Perspectives , 2012, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[25]  Dimitris Samaras,et al.  Two-person interaction detection using body-pose features and multiple instance learning , 2012, 2012 IEEE Computer Society Conference on Computer Vision and Pattern Recognition Workshops.

[26]  Lijun Liu,et al.  An efficient parallel neural network-based multi-instance learning algorithm , 2012, The Journal of Supercomputing.

[27]  Akira Saito,et al.  Automated gastric cancer diagnosis on H&E-stained sections; ltraining a classifier on a large scale with multiple instance machine learning , 2013, Medical Imaging.

[28]  Vishal Monga,et al.  DFDL: Discriminative feature-oriented dictionary learning for histopathological image classification , 2015, 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI).

[29]  Iasonas Kokkinos,et al.  Semantic Image Segmentation with Deep Convolutional Nets and Fully Connected CRFs , 2014, ICLR.

[30]  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).

[31]  Jaume Amores,et al.  Multiple instance classification: Review, taxonomy and comparative study , 2013, Artif. Intell..

[32]  Geoffrey E. Hinton,et al.  ImageNet classification with deep convolutional neural networks , 2012, Commun. ACM.

[33]  Yoshua Bengio,et al.  Gradient-based learning applied to document recognition , 1998, Proc. IEEE.

[34]  Trevor Darrell,et al.  Caffe: Convolutional Architecture for Fast Feature Embedding , 2014, ACM Multimedia.

[35]  Trevor Darrell,et al.  Fully Convolutional Multi-Class Multiple Instance Learning , 2014, ICLR.

[36]  Bahram Parvin,et al.  Stacked Predictive Sparse Decomposition for Classification of Histology Sections , 2014, International Journal of Computer Vision.

[37]  Paul A. Viola,et al.  Multiple Instance Boosting for Object Detection , 2005, NIPS.

[38]  Nasser M. Nasrabadi,et al.  Pattern Recognition and Machine Learning , 2006, Technometrics.

[39]  Anonymous Authors Empowering Multiple Instance Histopathology Cancer Diagnosis by Cell Graphs , 2014 .

[40]  Simon Haykin,et al.  GradientBased Learning Applied to Document Recognition , 2001 .

[41]  Carsten Rother,et al.  Weakly supervised discriminative localization and classification: a joint learning process , 2009, 2009 IEEE 12th International Conference on Computer Vision.