Histopathology Stain-Color Normalization Using Deep Generative Models

Farhad G. Zanjani, Svitlana Zinger, Babak E. Bejnordi, Jeroen AWM van der Laak, Peter H.N. de With

Abstract: Performance of designed CAD algorithms for histopathology image analysis is affected by the amount of variations in the samples such as color and intensity of stained images. Stain-color normalization is a well-studied technique for compensating such effects at the input of CAD systems. In this paper, we introduce unsupervised generative neural networks for performing stain-color normalization. For color normalization in stained hematoxylin and eosin (H&E) images, we present three methods based on three frameworks for deep generative models: variational auto-encoder (VAE), generative adversarial networks (GAN) and deep convolutional Gaussian mixture models (DCGMM). Our contribution is defining the color normalization as a learning generative model that is able to generate various color copies of the input image through a nonlinear parametric transformation. In contrast to earlier generative models proposed for stain-color normalization, our approach does not need any labels for data or any other assumptions about the H&E image content. Furthermore, our models learn a parametric transformation during training and can convert the color information of an input image to resemble any arbitrary reference image. This property is essential in time-critical CAD systems in case of changing the reference image, since our approach does not need retraining in contrast to other proposed generative models for stain-color normalization. Experiments on histopathological H&E images with high staining variations, collected from different laboratories, show that our proposed models outperform quantitatively state-of-the-art methods in the measure of color constancy with at least 10-15%, while the converted images are visually in agreement with this performance improvement.

Author Affiliation: Eindhoven University of Technology

Keywords: Computational pathology, stain-color normalization, deep generative models, convolutional neural networks (CNN)