OCT2Hist: Non-Invasive Virtual Biopsy Using Optical Coherence Tomography

Histological haematoxylin and eosin-stained (H&E) tissue sections are used as the gold standard for pathologic detection of cancer, tumour margin detection, and disease diagnosis1. Producing H&E sections, however, is invasive and time-consuming. Non-invasive optical imaging modalities, such as optical coherence tomography (OCT), permit label-free, micron-scale 3D imaging of biological tissue microstructure with significant depth (up to 1mm) and large fields-of-view2, but are difficult to interpret and correlate with clinical ground truth without specialized training3. Here we introduce the concept of a virtual biopsy, using generative neural networks to synthesize virtual H&E sections from OCT images. To do so we have developed a novel technique, "optical barcoding", which has allowed us to repeatedly extract the 2D OCT slice from a 3D OCT volume that corresponds to a given H&E tissue section, with very high alignment precision down to 25 microns. Using 1,005 prospectively collected human skin sections from Mohs surgery operations of 71 patients, we constructed the largest dataset of H&E images and their corresponding precisely aligned OCT images, and trained a conditional generative adversarial network4 on these image pairs. Our results demonstrate the ability to use OCT images to generate high-fidelity virtual H&E sections and entire 3D H&E volumes. Applying this trained neural network to in vivo OCT images should enable physicians to readily incorporate OCT imaging into their clinical practice, reducing the number of unnecessary biopsy procedures.