Generative Adversarial Domain Adaptation for Nucleus Quantification in Images of Tissue Immunohistochemically Stained for Ki-67

PURPOSE: We focus on the problem of scarcity of annotated training data for nucleus recognition in Ki-67 immunohistochemistry (IHC)–stained pancreatic neuroendocrine tumor (NET) images. We hypothesize that deep learning–based domain adaptation is helpful for nucleus recognition when image annotations are unavailable in target data sets. METHODS: We considered 2 different institutional pancreatic NET data sets: one (ie, source) containing 38 cases with 114 annotated images and the other (ie, target) containing 72 cases with 20 annotated images. The gold standards were manually annotated by 1 pathologist. We developed a novel deep learning–based domain adaptation framework to count different types of nuclei (ie, immunopositive tumor, immunonegative tumor, nontumor nuclei). We compared the proposed method with several recent fully supervised deep learning models, such as fully convolutional network-8s (FCN-8s), U-Net, fully convolutional regression network (FCRN) A, FCRNB, and fully residual convolutional network (FRCN). We also evaluated the proposed method by learning with a mixture of converted source images and real target annotations. RESULTS: Our method achieved an F(1) score of 81.3% and 62.3% for nucleus detection and classification in the target data set, respectively. Our method outperformed FCN-8s (53.6% and 43.6% for nucleus detection and classification, respectively), U-Net (61.1% and 47.6%), FCRNA (63.4% and 55.8%), and FCRNB (68.2% and 60.6%) in terms of F(1) score and was competitive with FRCN (81.7% and 70.7%). In addition, learning with a mixture of converted source images and only a small set of real target labels could further boost the performance. CONCLUSION: This study demonstrates that deep learning–based domain adaptation is helpful for nucleus recognition in Ki-67 IHC stained images when target data annotations are not available. It would improve the applicability of deep learning models designed for downstream supervised learning tasks on different data sets.