Virtual stain transfer in histology via cascaded deep neural networks

Pathological diagnosis relies on the visual inspection of histologically stained thin tissue specimens, where different types of stains are applied to bring contrast to and highlight various desired histological features. However, the destructive histochemical staining procedures are usually irreversible, making it very difficult to obtain multiple stains on the same tissue section. Here, we demonstrate a virtual stain transfer framework via a cascaded deep neural network (C-DNN) to digitally transform hematoxylin and eosin (H&E) stained tissue images into other types of histological stains. Unlike a single neural network structure which only takes one stain type as input to digitally output images of another stain type, C-DNN first uses virtual staining to transform autofluorescence microscopy images into H&E and then performs stain transfer from H&E to the domain of the other stain in a cascaded manner. This cascaded structure in the training phase allows the model to directly exploit histochemically stained image data on both H&E and the target special stain of interest. This advantage alleviates the challenge of paired data acquisition and improves the image quality and color accuracy of the virtual stain transfer from H&E to another stain. We validated the superior performance of this C-DNN approach using kidney needle core biopsy tissue sections and successfully transferred the H&E-stained tissue images into virtual PAS (periodic acid-Schiff) stain. This method provides high-quality virtual images of special stains using existing, histochemically stained slides and creates new opportunities in digital pathology by performing highly accurate stain-to-stain transformations.