ABSTRACT For routine pathology diagnosis and imaging based biomedical research, Whole-Slide Image (WSI) analyses have been largely limited to a 2D tissue image space. For a more definitive tissue representation to support fine-resolution spatial and integrative analyses, it is critical to extend such tissue based investigations to a 3D tissue space with spatially aligned serial tissue WSIs in different stains, such as Hematoxylin and Eosin (H&amp;E) and Immunohistochemistry (IHC) biomarkers. However, such WSI registration is technically challenged by the overwhelming image scale, the complex histology structure change, and the significant difference in tissue appearances in different stains. We propose a novel translation based deep learning registration network CycGANRegNet that spatially aligns serial WSIs stained in H&amp;E and by IHC biomarkers without prior deformation information for the model training. First, synthetic IHC images are produced from H&amp;E slides through a robust image synthesis algorithm. Next, the synthetic and the real IHC images are registered through a Fully Convolutional Network with multi-scaled deformable vector fields and a joint loss optimization. We perform the registration at the full image resolution, retaining the tissue details in the results. Evaluated with a dataset of 76 breast cancer patients with one H&amp;E and two IHC serial WSIs for each patient, CycGANRegNet outperforms multiple state-of-the-art deep learning based and conventional pathology image registration methods. Our results suggest that CycGAN-RegNet can produce promising registration results with serial WSIs in different stains, enabling integrative 3D tissue-based biomedical investigations.

Deep Learning Based Registration of Serial Whole-slide Histopathology Images in Different Stains