Creating synthetic digital slides using conditional generative adversarial networks: application to Ki67 staining

Immunohistochemical staining (IHC) of tissue sections is routinely used in pathology to diagnose and characterize malignant tumors. Unfortunately, in the majority of cases, IHC stain interpretation is completed by a trained pathologist using a manual method, which consists of counting each positively and negatively stained cell under a microscope. Even in the hands of expert pathologists, the manual enumeration suffers from poor reproducibility. In this study, we propose a novel method to create artificial datasets in silico with known ground truth, allowing us to analyze the accuracy, precision, and intra- and inter-observer variability in a systematic manner and compare different computer analysis approaches. Our approach employs conditional Generative Adversarial Networks. We created our dataset by using 32 different breast cancer patients' Ki67 stained tissues. Our experiments indicated that synthetic images are indistinguishable from real images: The accuracy of five experts (3 pathologists and 2 image analysts) in distinguishing between 15 real and 15 synthetic images was only 47.3% (±8.5%).