Image Descriptors for Weakly Annotated Histopathological Breast Cancer Data

Introduction: Cancerous Tissue Recognition (CTR) methodologies are continuously integrating advancements at the forefront of machine learning and computer vision, providing a variety of inference schemes for histopathological data. Histopathological data, in most cases, come in the form of high-resolution images, and thus methodologies operating at the patch level are more computationally attractive. Such methodologies capitalize on pixel level annotations (tissue delineations) from expert pathologists, which are then used to derive labels at the patch level. In this work, we envision a digital connected health system that augments the capabilities of the clinicians by providing powerful feature descriptors that may describe malignant regions. Material and Methods: We start with a patch level descriptor, termed Covariance-Kernel Descriptor (CKD), capable of compactly describing tissue architectures associated with carcinomas. To leverage the recognition capability of the CKDs to larger slide regions, we resort to a multiple instance learning framework. In that direction, we derive the Weakly Annotated Image Descriptor (WAID) as the parameters of classifier decision boundaries in a Multiple Instance Learning framework. The WAID is computed on bags of patches corresponding to larger image regions for which binary labels (malignant vs. benign) are provided, thus obviating the necessity for tissue delineations. Results: The CKD was seen to outperform all the considered descriptors, reaching classification accuracy (ACC) of 92.83%. and area under the curve (AUC) of 0.98. The CKD captures higher order correlations between features and was shown to achieve superior performance against a large collection of computer vision features on a private breast cancer dataset. The WAID outperform all other descriptors on the Breast Cancer Histopathological database (BreakHis) where correctly classified malignant (CCM) instances reached 91.27 and 92.00% at the patient and image level, respectively, without resorting to a deep learning scheme achieves state-of-the-art performance. Discussion: Our proposed derivation of the CKD and WAID can help medical experts accomplish their work accurately and faster than the current state-of-the-art.

[1]  Gary Doran,et al.  A theoretical and empirical analysis of support vector machine methods for multiple-instance classification , 2014, Machine Learning.

[2]  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.

[3]  A. Fischer,et al.  Hematoxylin and eosin staining of tissue and cell sections. , 2008, CSH protocols.

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

[5]  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.

[6]  Anoop Cherian,et al.  Action Representation Using Classifier Decision Boundaries , 2017, ArXiv.

[7]  Nico Karssemeijer,et al.  Automated Detection of DCIS in Whole-Slide H&E Stained Breast Histopathology Images , 2016, IEEE Transactions on Medical Imaging.

[8]  Fatih Murat Porikli,et al.  Covariance Tracking using Model Update Based on Lie Algebra , 2006, 2006 IEEE Computer Society Conference on Computer Vision and Pattern Recognition (CVPR'06).

[9]  Fatih Murat Porikli,et al.  Region Covariance: A Fast Descriptor for Detection and Classification , 2006, ECCV.

[10]  Andrew Zisserman,et al.  Efficient additive kernels via explicit feature maps , 2010, 2010 IEEE Computer Society Conference on Computer Vision and Pattern Recognition.

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

[12]  Geoffrey E. Hinton,et al.  Visualizing Data using t-SNE , 2008 .

[13]  Anant Madabhushi,et al.  Multi-Field-of-View Framework for Distinguishing Tumor Grade in ER+ Breast Cancer From Entire Histopathology Slides , 2013, IEEE Transactions on Biomedical Engineering.

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

[15]  Andrew Zisserman,et al.  Very Deep Convolutional Networks for Large-Scale Image Recognition , 2014, ICLR.

[16]  Nicholas A. Hamilton,et al.  Fast automated cell phenotype image classification , 2007, BMC Bioinformatics.

[17]  Luiz Eduardo Soares de Oliveira,et al.  Breast cancer histopathological image classification using Convolutional Neural Networks , 2016, 2016 International Joint Conference on Neural Networks (IJCNN).

[18]  Anoop Cherian,et al.  Learning Discriminative Video Representations Using Adversarial Perturbations , 2018, ECCV.

[19]  Christine Decaestecker,et al.  Strategies to Reduce the Expert Supervision Required for Deep Learning-Based Segmentation of Histopathological Images , 2019, Front. Med..

[20]  Alireza Tavakoli Targhi,et al.  THE KTH-TIPS 2 database , 2006 .

[21]  Dumitru Erhan,et al.  Going deeper with convolutions , 2014, 2015 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[22]  N. Ayache,et al.  Log‐Euclidean metrics for fast and simple calculus on diffusion tensors , 2006, Magnetic resonance in medicine.

[23]  Subhransu Maji,et al.  Classification using intersection kernel support vector machines is efficient , 2008, 2008 IEEE Conference on Computer Vision and Pattern Recognition.

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

[25]  Patty Kostkova,et al.  Grand Challenges in Digital Health , 2015, Front. Public Health.

[26]  Vassilios Morellas,et al.  Evaluation of feature descriptors for cancerous tissue recognition , 2016, 2016 23rd International Conference on Pattern Recognition (ICPR).

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

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

[29]  Razvan C. Bunescu,et al.  Multiple instance learning for sparse positive bags , 2007, ICML '07.

[30]  Anoop Cherian,et al.  Jensen-Bregman LogDet Divergence with Application to Efficient Similarity Search for Covariance Matrices , 2013, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[31]  H. Irshad,et al.  Methods for Nuclei Detection, Segmentation, and Classification in Digital Histopathology: A Review—Current Status and Future Potential , 2014, IEEE Reviews in Biomedical Engineering.

[32]  Ju Jia Zou,et al.  Adapting fisher vectors for histopathology image classification , 2017, 2017 IEEE 14th International Symposium on Biomedical Imaging (ISBI 2017).

[33]  Luiz Eduardo Soares de Oliveira,et al.  A Dataset for Breast Cancer Histopathological Image Classification , 2016, IEEE Transactions on Biomedical Engineering.

[34]  Abhijit Guha Roy,et al.  Classifying histopathology whole-slides using fusion of decisions from deep convolutional network on a collection of random multi-views at multi-magnification , 2017, 2017 IEEE 14th International Symposium on Biomedical Imaging (ISBI 2017).

[35]  Felix X. Yu,et al.  SVM for learning with label proportions , 2013, ICML 2013.