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We report label-free, in vivo virtual histology of skin using reflectance confocal microscopy (RCM). We trained a deep neural network to transform in vivo RCM images of unstained skin into virtually stained H&E-like microscopic images with nuclear contrast. This framework successfully generalized to diverse skin conditions, e.g., normal skin, basal cell carcinoma, and melanocytic nevi, as well as distinct skin layers, including the epidermis, dermal-epidermal junction, and superficial dermis layers. This label-free in vivo skin virtual histology framework can be transformative for faster and more accurate diagnosis of malignant skin neoplasms, with the potential to significantly reduce unnecessary skin biopsies. 

Reflectance confocal microscopy (RCM) can provide in vivo images of the skin with cellular-level resolution; however, RCM images are grayscale, lack nuclear features and have a low correlation with histology. We present a deep learning-based virtual staining method to perform non-invasive virtual histology of the skin based on in vivo, label-free RCM images. This virtual histology framework revealed successful inference for various skin conditions, such as basal cell carcinoma, also covering distinct skin layers, including epidermis and dermal-epidermal junction. This method can pave the way for faster and more accurate diagnosis of malignant skin neoplasms while reducing unnecessary biopsies. 

We reportin vivovirtual histology of skin without a biopsy, where deep learning is used to virtually stain tissue and generate hematoxylin and eosin (H&E)-like microscopic images of skin using a reflectance confocal microscope. 

The immunohistochemical (IHC) staining of the human epidermal growth factor receptor 2 (HER2) biomarker is widely practiced in breast tissue analysis, preclinical studies, and diagnostic decisions, guiding cancer treatment and investigation of pathogenesis. HER2 staining demands laborious tissue treatment and chemical processing performed by a histotechnologist, which typically takes one day to prepare in a laboratory, increasing analysis time and associated costs. Here, we describe a deep learning-based virtual HER2 IHC staining method using a conditional generative adversarial network that is trained to rapidly transform autofluorescence microscopic images of unlabeled/label-free breast tissue sections into bright-field equivalent microscopic images, matching the standard HER2 IHC staining that is chemically performed on the same tissue sections. The efficacy of this virtual HER2 staining framework was demonstrated by quantitative analysis, in which three board-certified breast pathologists blindly graded the HER2 scores of virtually stained and immunohistochemically stained HER2 whole slide images (WSIs) to reveal that the HER2 scores determined by inspecting virtual IHC images are as accurate as their immunohistochemically stained counterparts. A second quantitative blinded study performed by the same diagnosticians further revealed that the virtually stained HER2 images exhibit a comparable staining quality in the level of nuclear detail, membrane clearness, and absence of staining artifacts with respect to their immunohistochemically stained counterparts. This virtual HER2 staining framework bypasses the costly, laborious, and time-consuming IHC staining procedures in laboratory and can be extended to other types of biomarkers to accelerate the IHC tissue staining used in life sciences and biomedical workflow. 

We present deep learning-based virtual immunohistochemical (IHC) HER2 staining of label-free breast tissue sections, matching the standard IHC HER2 staining performed by histotechnologists.