Deep Learning Global Glomerulosclerosis in Transplant Kidney Frozen Sections

Transplantable kidneys are in very limited supply. Accurate viability assessment prior to transplantation could minimize organ discard. Rapid and accurate evaluation of intra-operative donor kidney biopsies is essential for determining which kidneys are eligible for transplantation. The criteria for accepting or rejecting donor kidneys relies heavily on pathologist determination of the percent of glomeruli (determined from a frozen section) that are normal and sclerotic. This percentage is a critical measurement that correlates with transplant outcome. Inter- and intra-observer variability in donor biopsy evaluation is, however, significant. An automated method for determination of percent global glomerulosclerosis could prove useful in decreasing evaluation variability, increasing throughput, and easing the burden on pathologists. Here, we describe the development of a deep learning model that identifies and classifies non-sclerosed and sclerosed glomeruli in whole-slide images of donor kidney frozen section biopsies. This model extends a convolutional neural network (CNN) pre-trained on a large database of digital images. The extended model, when trained on just 48 whole slide images, exhibits slide-level evaluation performance on par with expert renal pathologists. The model substantially outperforms a model trained on image patches of isolated glomeruli. Encouragingly, the model’s performance is robust to slide preparation artifacts associated with frozen section preparation. As the first model reported that identifies and classifies normal and sclerotic glomeruli in frozen kidney sections, and thus the first model reported in the literature relevant to kidney transplantation, it may become an essential part of donor kidney biopsy evaluation in the clinical setting.

[1]  Emmanuelle Gouillart,et al.  scikit-image: image processing in Python , 2014, PeerJ.

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

[3]  Olaf Hellwich,et al.  Deep convolutional neural networks for automatic classification of gastric carcinoma using whole slide images in digital histopathology , 2017, Comput. Medical Imaging Graph..

[4]  Rabi Yacoub,et al.  Unsupervised labeling of glomerular boundaries using Gabor filters and statistical testing in renal histology , 2017, Journal of medical imaging.

[5]  B. Dimitrov,et al.  Long-Term Outcome of Renal Transplantation from Older Donors , 2006 .

[6]  Yoshihiro Hirohashi,et al.  Segmental HOG: new descriptor for glomerulus detection in kidney microscopy image , 2015, BMC Bioinformatics.

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

[8]  Barry I Freedman,et al.  Histopathologic findings associated with APOL1 risk variants in chronic kidney disease , 2015, Modern Pathology.

[9]  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).

[10]  K. Aldape,et al.  Precision histology: how deep learning is poised to revitalize histomorphology for personalized cancer care , 2017, npj Precision Oncology.

[11]  Germain Forestier,et al.  Detection of glomeruli in renal pathology by mutual comparison of multiple staining modalities , 2017, Proceedings of the 10th International Symposium on Image and Signal Processing and Analysis.

[12]  Anthony Castleberry,et al.  Trends in Usage and Outcomes for Expanded Criteria Donor Kidney Transplantation in the United States Characterized by Kidney Donor Profile Index , 2016, Cureus.

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

[14]  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.

[15]  S. Samsi,et al.  Glomeruli segmentation in H&E stained tissue using perceptual organization , 2012, 2012 IEEE Signal Processing in Medicine and Biology Symposium (SPMB).

[16]  Gloria Bueno,et al.  Glomerulus Classification with Convolutional Neural Networks , 2017, MIUA.

[17]  Nilanjan Dey,et al.  Measurement of glomerulus diameter and Bowman's space width of renal albino rats , 2016, Comput. Methods Programs Biomed..

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

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

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

[21]  Ali Tahir,et al.  Classification Of Breast Cancer Histology Images Using ALEXNET , 2018, ICIAR.

[22]  Michael Gadermayr,et al.  CNN Cascades for Segmenting Whole Slide Images of the Kidney , 2017, Comput. Medical Imaging Graph..

[23]  S. Bagnasco,et al.  Banff Histopathological Consensus Criteria for Preimplantation Kidney Biopsies , 2016, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[24]  Jacques Pirenne,et al.  Graft quality assessment in kidney transplantation: not an exact science yet! , 2011, Current opinion in organ transplantation.

[25]  Daniel L. Rubin,et al.  Automated Grading of Gliomas using Deep Learning in Digital Pathology Images: A modular approach with ensemble of convolutional neural networks , 2015, AMIA.

[26]  Jun Zhang,et al.  Glomerulus Extraction by Optimizing the Fitting Curve , 2008, 2008 International Symposium on Computational Intelligence and Design.

[27]  Vladlen Koltun,et al.  Multi-Scale Context Aggregation by Dilated Convolutions , 2015, ICLR.

[28]  Francesc Moreso,et al.  The reproducibility and predictive value on outcome of renal biopsies from expanded criteria donors. , 2014, Kidney international.

[29]  Yan Zhao,et al.  Automatic glomerulus extraction in whole slide images towards computer aided diagnosis , 2016, 2016 IEEE 12th International Conference on e-Science (e-Science).

[30]  Tony Lindeberg,et al.  Detecting salient blob-like image structures and their scales with a scale-space primal sketch: A method for focus-of-attention , 1993, International Journal of Computer Vision.

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

[32]  Johannes E. Schindelin,et al.  Fiji: an open-source platform for biological-image analysis , 2012, Nature Methods.

[33]  N Taub,et al.  International variation in the interpretation of renal transplant biopsies: report of the CERTPAP Project. , 2001, Kidney international.

[34]  J. Wetzels,et al.  Long-term outcome of renal transplantation from older donors. , 2006, The New England journal of medicine.

[35]  Iasonas Kokkinos,et al.  DeepLab: Semantic Image Segmentation with Deep Convolutional Nets, Atrous Convolution, and Fully Connected CRFs , 2016, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[36]  D. Droz,et al.  A Simple Clinico‐Histopathological Composite Scoring System Is Highly Predictive of Graft Outcomes in Marginal Donors , 2008, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[37]  Catarina Eloy,et al.  Classification of breast cancer histology images using Convolutional Neural Networks , 2017, PloS one.

[38]  Jean-Christophe Olivo-Marin,et al.  An approach for detection of glomeruli in multisite digital pathology , 2016, 2016 IEEE 13th International Symposium on Biomedical Imaging (ISBI).

[39]  Bryan F. Cox,et al.  Computer-assisted imaging algorithms facilitate histomorphometric quantification of kidney damage in rodent renal failure models , 2012, Journal of pathology informatics.

[40]  A. Demetris,et al.  Biopsy of marginal donor kidneys: correlation of histologic findings with graft dysfunction. , 2000, Transplantation.

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

[42]  Tao Huang,et al.  Genetic algorithm for edge extraction of glomerulus area , 2004, International Conference on Information Acquisition, 2004. Proceedings..

[43]  Sebastian Thrun,et al.  Dermatologist-level classification of skin cancer with deep neural networks , 2017, Nature.

[44]  Angelo Duarte,et al.  PathoSpotter-K: A computational tool for the automatic identification of glomerular lesions in histological images of kidneys , 2017, Scientific Reports.

[45]  John E. Tomaszewski,et al.  Automated renal histopathology: digital extraction and quantification of renal pathology , 2016, SPIE Medical Imaging.

[46]  Jinglu Hu,et al.  Glomerulus extraction by using genetic algorithm for edge patching , 2009, 2009 IEEE Congress on Evolutionary Computation.

[47]  Yoshihiro Hirohashi,et al.  Automated image analysis of a glomerular injury marker desmin in spontaneously diabetic Torii rats treated with losartan. , 2014, The Journal of endocrinology.

[48]  Rabi Yacoub,et al.  Multi-radial LBP Features as a Tool for Rapid Glomerular Detection and Assessment in Whole Slide Histopathology Images , 2017, Scientific Reports.

[49]  E. Perencevich,et al.  The Maryland Aggregate Pathology Index: A Deceased Donor Kidney Biopsy Scoring System for Predicting Graft Failure , 2008, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.