Fast and Accurate Tumor Segmentation of Histology Images using Persistent Homology and Deep Convolutional Features

Tumor segmentation in whole-slide images of histology slides is an important step towards computer-assisted diagnosis. In this work, we propose a tumor segmentation framework based on the novel concept of persistent homology profiles (PHPs). For a given image patch, the homology profiles are derived by efficient computation of persistent homology, which is an algebraic tool from homology theory. We propose an efficient way of computing topological persistence of an image, alternative to simplicial homology. The PHPs are devised to distinguish tumor regions from their normal counterparts by modeling the atypical characteristics of tumor nuclei. We propose two variants of our method for tumor segmentation: one that targets speed without compromising accuracy and the other that targets higher accuracy. The fast version is based on a selection of exemplar image patches from a convolution neural network (CNN) and patch classification by quantifying the divergence between the PHPs of exemplars and the input image patch. Detailed comparative evaluation shows that the proposed algorithm is significantly faster than competing algorithms while achieving comparable results. The accurate version combines the PHPs and high-level CNN features and employs a multi-stage ensemble strategy for image patch labeling. Experimental results demonstrate that the combination of PHPs and CNN features outperform competing algorithms. This study is performed on two independently collected colorectal datasets containing adenoma, adenocarcinoma, signet, and healthy cases. Collectively, the accurate tumor segmentation produces the highest average patch-level F1-score, as compared with competing algorithms, on malignant and healthy cases from both the datasets. Overall the proposed framework highlights the utility of persistent homology for histopathology image analysis.

[1]  Kelin Xia,et al.  Persistent homology analysis of protein structure, flexibility, and folding , 2014, International journal for numerical methods in biomedical engineering.

[2]  S. Mukherjee,et al.  Persistent Homology Transform for Modeling Shapes and Surfaces , 2013, 1310.1030.

[3]  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.

[4]  Ramakrishnan Mukundan,et al.  HER2 challenge contest: a detailed assessment of automated HER2 scoring algorithms in whole slide images of breast cancer tissues , 2017, Histopathology.

[5]  Thomas Brox,et al.  U-Net: Convolutional Networks for Biomedical Image Segmentation , 2015, MICCAI.

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

[7]  Francesco Bianconi,et al.  Discrimination between tumour epithelium and stroma via perception-based features , 2015, Neurocomputing.

[8]  Jun Kong,et al.  Digital Pathology: Data-Intensive Frontier in Medical Imaging , 2012, Proceedings of the IEEE.

[9]  Kazuaki Nakane,et al.  Homology-based method for detecting regions of interest in colonic digital images , 2015, Diagnostic Pathology.

[10]  R. Ghrist Barcodes: The persistent topology of data , 2007 .

[11]  A. Madabhushi,et al.  Histopathological Image Analysis: A Review , 2009, IEEE Reviews in Biomedical Engineering.

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

[13]  A. Jemal,et al.  Global Cancer Statistics , 2011 .

[14]  Gunnar E. Carlsson,et al.  Topology and data , 2009 .

[15]  Michael I. Jordan,et al.  Loopy Belief Propagation for Approximate Inference: An Empirical Study , 1999, UAI.

[16]  B. van Ginneken,et al.  Deep learning as a tool for increased accuracy and efficiency of histopathological diagnosis , 2016, Scientific Reports.

[17]  N. Rajpoot,et al.  HyMaP: A hybrid magnitude-phase approach to unsupervised segmentation of tumor areas in breast cancer histology images , 2013, Journal of pathology informatics.

[18]  K. Alitalo,et al.  Assessment of tumour viability in human lung cancer xenografts with texture-based image analysis , 2015, Journal of Clinical Pathology.

[19]  Stephen J. McKenna,et al.  Tumor localization in tissue microarrays using rotation invariant superpixel pyramids , 2015, 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI).

[20]  Yee-Wah Tsang,et al.  Validation of digital pathology imaging for primary histopathological diagnosis , 2016, Histopathology.

[21]  Xiaojin Zhu,et al.  Persistent Homology: An Introduction and a New Text Representation for Natural Language Processing , 2013, IJCAI.

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

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

[24]  Nasir M. Rajpoot,et al.  Learning Where to See: A Novel Attention Model for Automated Immunohistochemical Scoring , 2019, IEEE Transactions on Medical Imaging.

[25]  Hao Chen,et al.  DCAN: Deep contour‐aware networks for object instance segmentation from histology images , 2017, Medical Image Anal..

[26]  Mark Lawler,et al.  Challenging the Cancer Molecular Stratification Dogma: Intratumoral Heterogeneity Undermines Consensus Molecular Subtypes and Potential Diagnostic Value in Colorectal Cancer , 2016, Clinical Cancer Research.

[27]  Rob Fergus,et al.  Visualizing and Understanding Convolutional Networks , 2013, ECCV.

[28]  Kazuaki Nakane,et al.  A simple mathematical model utilizing topological invariants for automatic detection of tumor areas in digital tissue images , 2013, Diagnostic Pathology.

[29]  Mason A. Porter,et al.  A roadmap for the computation of persistent homology , 2015, EPJ Data Science.

[30]  Geoffrey E. Hinton,et al.  Dynamic Routing Between Capsules , 2017, NIPS.

[31]  Vijay Kumar,et al.  Persistent Homology for Path Planning in Uncertain Environments , 2015, IEEE Transactions on Robotics.

[32]  Stefan M Willems,et al.  The estimation of tumor cell percentage for molecular testing by pathologists is not accurate , 2014, Modern Pathology.

[33]  Sepp Hochreiter,et al.  Fast and Accurate Deep Network Learning by Exponential Linear Units (ELUs) , 2015, ICLR.

[34]  Herbert Edelsbrunner,et al.  The Classification of Endoscopy Images with Persistent Homology , 2014, 2014 16th International Symposium on Symbolic and Numeric Algorithms for Scientific Computing.

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

[36]  Carina Curto,et al.  What can topology tell us about the neural code , 2016, 1605.01905.

[37]  David L Rimm,et al.  A prospective, multi-institutional diagnostic trial to determine pathologist accuracy in estimation of percentage of malignant cells. , 2013, Archives of pathology & laboratory medicine.

[38]  S. Shankar Sastry,et al.  Dissimilarity-Based Sparse Subset Selection , 2015, IEEE Trans. Pattern Anal. Mach. Intell..

[39]  Nikos Komodakis,et al.  Paying More Attention to Attention: Improving the Performance of Convolutional Neural Networks via Attention Transfer , 2016, ICLR.

[40]  J. Harshbarger Comparative oncology. , 1996, Japanese journal of cancer research : Gann.

[41]  S. Shankar Sastry,et al.  Dissimilarity-Based Sparse Subset Selection , 2014, IEEE Transactions on Pattern Analysis and Machine Intelligence.

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

[43]  Francesco Bianconi,et al.  Multi-class texture analysis in colorectal cancer histology , 2016, Scientific Reports.

[44]  Guillermo Sapiro,et al.  Finding Exemplars from Pairwise Dissimilarities via Simultaneous Sparse Recovery , 2012, NIPS.

[45]  Guo-Wei Wei,et al.  Integration of element specific persistent homology and machine learning for protein‐ligand binding affinity prediction , 2018, International journal for numerical methods in biomedical engineering.

[46]  David B. A. Epstein,et al.  Tumor Segmentation in Whole Slide Images Using Persistent Homology and Deep Convolutional Features , 2017, MIUA.

[47]  Shabanam S. Tamboli,et al.  Histopathological Image Analysis for Breast Cancer Diagnosis : A Review , .

[48]  Anant Madabhushi,et al.  Accurate and reproducible invasive breast cancer detection in whole-slide images: A Deep Learning approach for quantifying tumor extent , 2017, Scientific Reports.

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

[50]  David B. A. Epstein,et al.  Persistent Homology for Fast Tumor Segmentation in Whole Slide Histology Images , 2016, MIUA.

[51]  J. Marron,et al.  Persistent Homology Analysis of Brain Artery Trees. , 2014, The annals of applied statistics.

[52]  K M Søndergaard,et al.  [Understanding statistics?]. , 1995, Ugeskrift for laeger.

[53]  Clustering Survival Data using Random Forest and Persistent Homology , 2016 .

[54]  R. M. Simpson,et al.  Quantifying histological features of cancer biospecimens for biobanking quality assurance using automated morphometric pattern recognition image analysis algorithms. , 2011, Journal of biomolecular techniques : JBT.

[55]  E. Abt Understanding statistics 3 , 2010, Evidence-Based Dentistry.

[56]  H. Kamel,et al.  Trends and Challenges in Pathology Practice: Choices and necessities. , 2011, Sultan Qaboos University medical journal.

[57]  Matti Pietikäinen,et al.  Identification of tumor epithelium and stroma in tissue microarrays using texture analysis , 2012, Diagnostic Pathology.

[58]  H. Edelsbrunner,et al.  Persistent Homology — a Survey , 2022 .

[59]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[60]  Florian T. Pokorny,et al.  Topological trajectory classification with filtrations of simplicial complexes and persistent homology , 2016, Int. J. Robotics Res..

[61]  J. Ferlay,et al.  Estimates of cancer incidence and mortality in Europe in 2008. , 2010, European journal of cancer.

[62]  Rocío González-Díaz,et al.  Persistent homology-based gait recognition robust to upper body variations , 2016, 2016 23rd International Conference on Pattern Recognition (ICPR).