Localization of Diagnostically Relevant Regions of Interest in Whole Slide Images: a Comparative Study

Whole slide digital imaging technology enables researchers to study pathologists’ interpretive behavior as they view digital slides and gain new understanding of the diagnostic medical decision-making process. In this study, we propose a simple yet important analysis to extract diagnostically relevant regions of interest (ROIs) from tracking records using only pathologists’ actions as they viewed biopsy specimens in the whole slide digital imaging format (zooming, panning, and fixating). We use these extracted regions in a visual bag-of-words model based on color and texture features to predict diagnostically relevant ROIs on whole slide images. Using a logistic regression classifier in a cross-validation setting on 240 digital breast biopsy slides and viewport tracking logs of three expert pathologists, we produce probability maps that show 74 % overlap with the actual regions at which pathologists looked. We compare different bag-of-words models by changing dictionary size, visual word definition (patches vs. superpixels), and training data (automatically extracted ROIs vs. manually marked ROIs). This study is a first step in understanding the scanning behaviors of pathologists and the underlying reasons for diagnostic errors.

[1]  Claus Bahlmann,et al.  Automated detection of diagnostically relevant regions in H&E stained digital pathology slides , 2012, Medical Imaging.

[2]  Anant Madabhushi,et al.  AUTOMATED GRADING OF PROSTATE CANCER USING ARCHITECTURAL AND TEXTURAL IMAGE FEATURES , 2007, 2007 4th IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[3]  Linda G. Shapiro,et al.  Localization of Diagnostically Relevant Regions of Interest in Whole Slide Images: a Comparative Study , 2014, 2014 22nd International Conference on Pattern Recognition.

[4]  Humayun Irshad,et al.  Automated mitosis detection using texture, SIFT features and HMAX biologically inspired approach , 2013, Journal of pathology informatics.

[5]  Darren Treanor,et al.  Tracking with virtual slides: a tool to study diagnostic error in histopathology , 2009, Histopathology.

[6]  Metin Nafi Gürcan,et al.  An efficient computational framework for the analysis of whole slide images: Application to follicular lymphoma immunohistochemistry , 2012, J. Comput. Sci..

[7]  Nassir Navab,et al.  Automated malignancy detection in breast histopathological images , 2012, Medical Imaging.

[8]  May D. Wang,et al.  Histological Image Feature Mining Reveals Emergent Diagnostic Properties for Renal Cancer , 2011, 2011 IEEE International Conference on Bioinformatics and Biomedicine.

[9]  Hamid Soltanian-Zadeh,et al.  Multiwavelet grading of pathological images of prostate , 2003, IEEE Transactions on Biomedical Engineering.

[10]  Kim L. Boyer,et al.  Computer-aided evaluation of neuroblastoma on whole-slide histology images: Classifying grade of neuroblastic differentiation , 2009, Pattern Recognit..

[11]  Mrinal K. Mandal,et al.  Automated Segmentation of the Melanocytes in Skin Histopathological Images , 2013, IEEE Journal of Biomedical and Health Informatics.

[12]  F. Markowetz,et al.  Quantitative Image Analysis of Cellular Heterogeneity in Breast Tumors Complements Genomic Profiling , 2012, Science Translational Medicine.

[13]  Anant Madabhushi,et al.  A Boosted Bayesian Multiresolution Classifier for Prostate Cancer Detection From Digitized Needle Biopsies , 2012, IEEE Transactions on Biomedical Engineering.

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

[15]  Anant Madabhushi,et al.  Automated gland and nuclei segmentation for grading of prostate and breast cancer histopathology , 2008, 2008 5th IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[16]  Bahram Parvin,et al.  Morphometic analysis of TCGA glioblastoma multiforme , 2011, BMC Bioinformatics.

[17]  Anant Madabhushi,et al.  Automated grading of breast cancer histopathology using spectral clustering with textural and architectural image features , 2008, 2008 5th IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[18]  Daniel Racoceanu,et al.  Multi-channels statistical and morphological features based mitosis detection in breast cancer histopathology , 2013, 2013 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

[19]  Tad T. Brunyé,et al.  Eye Movements as an Index of Pathologist Visual Expertise: A Pilot Study , 2014, PloS one.

[20]  Gary Longton,et al.  A framework for evaluating diagnostic discordance in pathology discovered during research studies. , 2014, Archives of pathology & laboratory medicine.

[21]  Donald L Weaver,et al.  Understanding diagnostic variability in breast pathology: lessons learned from an expert consensus review panel , 2014, Histopathology.

[22]  J. Elmore,et al.  Diagnostic concordance among pathologists interpreting breast biopsy specimens. , 2015, JAMA.

[23]  Joel H. Saltz,et al.  Machine-Based Morphologic Analysis of Glioblastoma Using Whole-Slide Pathology Images Uncovers Clinically Relevant Molecular Correlates , 2013, PloS one.

[24]  Nico Karssemeijer,et al.  A multi-scale superpixel classification approach to the detection of regions of interest in whole slide histopathology images , 2015, Medical Imaging.

[25]  Joel H. Saltz,et al.  Histopathological Image Analysis Using Model-Based Intermediate Representations and Color Texture: Follicular Lymphoma Grading , 2009, J. Signal Process. Syst..

[26]  Gary Longton,et al.  Development of a diagnostic test set to assess agreement in breast pathology: practical application of the Guidelines for Reporting Reliability and Agreement Studies (GRRAS) , 2013, BMC Women's Health.

[27]  Andrew Zisserman,et al.  Efficient Visual Search of Videos Cast as Text Retrieval , 2009, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[28]  R. Glaser,et al.  Expertise in a complex skill: Diagnosing x-ray pictures. , 1988 .

[29]  Pascal Fua,et al.  SLIC Superpixels Compared to State-of-the-Art Superpixel Methods , 2012, IEEE Transactions on Pattern Analysis and Machine Intelligence.

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

[31]  Metin Nafi Gürcan,et al.  Computerized classification of intraductal breast lesions using histopathological images , 2011, IEEE Transactions on Biomedical Engineering.

[32]  Xu Liu,et al.  Wavelet-based statistical features for distinguishing mitotic and non-mitotic cells in breast cancer histopathology , 2014, 2014 IEEE International Conference on Image Processing (ICIP).

[33]  Padraig Cunningham,et al.  Ensemble based system for whole-slide prostate cancer probability mapping using color texture features , 2011, Comput. Medical Imaging Graph..

[34]  D.M. Mount,et al.  An Efficient k-Means Clustering Algorithm: Analysis and Implementation , 2002, IEEE Trans. Pattern Anal. Mach. Intell..

[35]  Hideyuki Tamura,et al.  Textural Features Corresponding to Visual Perception , 1978, IEEE Transactions on Systems, Man, and Cybernetics.

[36]  Jitendra Malik,et al.  Learning a classification model for segmentation , 2003, Proceedings Ninth IEEE International Conference on Computer Vision.

[37]  Joachim M. Buhmann,et al.  Computational Pathology Analysis of Tissue Microarrays Predicts Survival of Renal Clear Cell Carcinoma Patients , 2008, MICCAI.

[38]  C. Koch,et al.  Computational modelling of visual attention , 2001, Nature Reviews Neuroscience.

[39]  Mrinal K. Mandal,et al.  Automated segmentation and analysis of the epidermis area in skin histopathological images , 2012, 2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[40]  J P Vink,et al.  Efficient nucleus detector in histopathology images , 2013, Journal of microscopy.

[41]  Dong-Chen He,et al.  Texture Unit, Texture Spectrum And Texture Analysis , 1989, 12th Canadian Symposium on Remote Sensing Geoscience and Remote Sensing Symposium,.

[42]  Andrew H. Beck,et al.  Computational Pathology to Discriminate Benign from Malignant Intraductal Proliferations of the Breast , 2014, PloS one.

[43]  Andrew Evans,et al.  Digital imaging in pathology: whole-slide imaging and beyond. , 2013, Annual review of pathology.

[44]  Jian Xian,et al.  Combined image and genomic analysis of high-grade serous ovarian cancer reveals PTEN loss as a common driver event and prognostic classifier , 2014, Genome Biology.

[45]  Andrew H. Beck,et al.  Systematic Analysis of Breast Cancer Morphology Uncovers Stromal Features Associated with Survival , 2011, Science Translational Medicine.

[46]  Cenk Sokmensuer,et al.  Automatic segmentation of colon glands using object-graphs , 2010, Medical Image Anal..

[47]  Kim L. Boyer,et al.  IMAGE ANALYSIS FOR AUTOMATED ASSESSMENT OF GRADE OF NEUROBLASTIC DIFFERENTIATION , 2007, 2007 4th IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[48]  Mikhail Teverovskiy,et al.  Multifeature Prostate Cancer Diagnosis and Gleason Grading of Histological Images , 2007, IEEE Transactions on Medical Imaging.

[49]  Elizabeth Genega,et al.  Network cycle features: Application to computer-aided Gleason grading of prostate cancer histopathological images , 2011, 2011 IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[50]  Nicolas Loménie,et al.  Time-efficient sparse analysis of histopathological whole slide images , 2011, Comput. Medical Imaging Graph..

[51]  Shahriar Gharibzadeh,et al.  Computer aided measurement of melanoma depth of invasion in microscopic images. , 2014, Micron.

[52]  Eduardo Romero,et al.  A supervised visual model for finding regions of interest in basal cell carcinoma images , 2011, Diagnostic pathology.

[53]  Eduardo Romero,et al.  Learning regions of interest from low level maps in virtual microscopy , 2011, Diagnostic pathology.

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

[55]  Daniel J. Brat,et al.  Novel genotype-phenotype associations in human cancers enabled by advanced molecular platforms and computational analysis of whole slide images , 2014, Laboratory Investigation.

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

[57]  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.

[58]  Linda G. Shapiro,et al.  Mouse cursor movement and eye tracking data as an indicator of pathologists’ attention when viewing digital whole slide images , 2012, Journal of pathology informatics.

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