StyPath: Style-Transfer Data Augmentation For Robust Histology Image Classification

The classification of Antibody Mediated Rejection (AMR) in kidney transplant remains challenging even for experienced nephropathologists; this is partly because histological tissue stain analysis is often characterized by low inter-observer agreement and poor reproducibility. One of the implicated causes for inter-observer disagreement is the variability of tissue stain quality between (and within) pathology labs, coupled with the gradual fading of archival sections. Variations in stain colors and intensities can make tissue evaluation difficult for pathologists, ultimately affecting their ability to describe relevant morphological features. Being able to accurately predict the AMR status based on kidney histology images is crucial for improving patient treatment and care. We propose a novel pipeline to build robust deep neural networks for AMR classification based on StyPath, a histological data augmentation technique that leverages a light weight style-transfer algorithm as a means to reduce sample-specific bias. Each image was generated in \(1.84 \pm 0.03\) s using a single GTX TITAN V gpu and pytorch, making it faster than other popular histological data augmentation techniques. We evaluated our model using a Monte Carlo (MC) estimate of Bayesian performance and generate an epistemic measure of uncertainty to compare both the baseline and StyPath augmented models. We also generated Grad-CAM representations of the results which were assessed by an experienced nephropathologist; we used this qualitative analysis to elucidate on the assumptions being made by each model. Our results imply that our style-transfer augmentation technique improves histological classification performance (reducing error from 14.8% to 11.5%) and generalization ability.

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

[2]  Abhishek Das,et al.  Grad-CAM: Visual Explanations from Deep Networks via Gradient-Based Localization , 2016, 2017 IEEE International Conference on Computer Vision (ICCV).

[3]  Zoubin Ghahramani,et al.  Bayesian Convolutional Neural Networks with Bernoulli Approximate Variational Inference , 2015, ArXiv.

[4]  Ghassan Hamarneh,et al.  Adversarial Stain Transfer for Histopathology Image Analysis , 2018, IEEE Transactions on Medical Imaging.

[5]  L. Truong,et al.  A Systematic Review of Interpathologist Agreement in Histologic Classification of Lupus Nephritis , 2019, Kidney international reports.

[6]  Nico Karssemeijer,et al.  Stain Specific Standardization of Whole-Slide Histopathological Images , 2016, IEEE Transactions on Medical Imaging.

[7]  Leon A. Gatys,et al.  A Neural Algorithm of Artistic Style , 2015, ArXiv.

[8]  Matthias Bethge,et al.  ImageNet-trained CNNs are biased towards texture; increasing shape bias improves accuracy and robustness , 2018, ICLR.

[9]  Geoffrey E. Hinton,et al.  Bayesian Learning for Neural Networks , 1995 .

[10]  Dorit Merhof,et al.  Context-Based Normalization of Histological Stains Using Deep Convolutional Features , 2017, DLMIA/ML-CDS@MICCAI.

[11]  Forrest N. Iandola,et al.  DenseNet: Implementing Efficient ConvNet Descriptor Pyramids , 2014, ArXiv.

[12]  M. Mengel,et al.  Banff Initiative for Quality Assurance in Transplantation (BIFQUIT): Reproducibility of Polyomavirus Immunohistochemistry in Kidney Allografts , 2014, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[13]  J. S. Marron,et al.  A method for normalizing histology slides for quantitative analysis , 2009, 2009 IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[14]  Aryan Mobiny,et al.  Risk-Aware Machine Learning Classifier for Skin Lesion Diagnosis , 2019, Journal of clinical medicine.

[15]  Geert J. S. Litjens,et al.  Quantifying the effects of data augmentation and stain color normalization in convolutional neural networks for computational pathology , 2019, Medical Image Anal..

[16]  Zoubin Ghahramani,et al.  Dropout as a Bayesian Approximation: Representing Model Uncertainty in Deep Learning , 2015, ICML.

[17]  T. Schaller,et al.  Interobserver variability in the H&E-based assessment of tumor budding in pT3/4 colon cancer: does it affect the prognostic relevance? , 2018, Virchows Archiv.

[18]  F. Offner,et al.  Tumor budding in colorectal cancer revisited: results of a multicenter interobserver study , 2015, Virchows Archiv.

[19]  Ron Wolterbeek,et al.  Interobserver agreement on histopathological lesions in class III or IV lupus nephritis. , 2015, Clinical journal of the American Society of Nephrology : CJASN.

[20]  Nassir Navab,et al.  Staingan: Stain Style Transfer for Digital Histological Images , 2018, 2019 IEEE 16th International Symposium on Biomedical Imaging (ISBI 2019).

[21]  Guigang Zhang,et al.  Deep Learning , 2016, Int. J. Semantic Comput..

[22]  Naveen Garg,et al.  DropConnect is effective in modeling uncertainty of Bayesian deep networks , 2019, Scientific Reports.