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Nuclei segmentation is a fundamental task that is critical for various computational pathology applications including nuclei morphology analysis, cell type classification, and cancer grading. Conventional vision-based methods for nuclei segmentation struggle in challenging cases and deep learning approaches have proven to be more robust and generalizable. However, CNNs require large amounts of labeled histopathology data. Moreover, conventional CNN-based approaches lack structured prediction capabilities which are required to distinguish overlapping and clumped nuclei. Here, we present an approach to nuclei segmentation that overcomes these challenges by utilizing a conditional generative adversarial network (cGAN) trained with synthetic and real data. We generate a large dataset of H&E training images with perfect nuclei segmentation labels using an unpaired GAN framework. This synthetic data along with real histopathology data from six different organs are used to train a conditional GAN with spectral normalization and gradient penalty for nuclei segmentation. This adversarial regression framework enforces higher order consistency when compared to conventional CNN models. We demonstrate that this nuclei segmentation approach generalizes across different organs, sites, patients and disease states, and outperforms conventional approaches, especially in isolating individual and overlapping nuclei.

Colorectal cancer is the second leading cause of cancer deaths in the United States and causes over 50,000 deaths annually. The standard of care for colorectal cancer detection and prevention is an optical colonoscopy and polypectomy. However, over 20% of the polyps are typically missed during a standard colonoscopy procedure and 60% of colorectal cancer cases are attributed to these missed polyps. Surface topography plays a vital role in identification and characterization of lesions, but topographic features often appear subtle to a conventional endoscope. Chromoendoscopy can highlight topographic features of the mucosa and has shown to improve lesion detection rate, but requires dedicated training and increases procedure time. Photometric stereo endoscopy captures this topography but is qualitative due to unknown working distances from each point of mucosa to the endoscope. In this work, we use deep learning to estimate a depth map from an endoscope camera with four alternating light sources. Since endoscopy videos with ground truth depth maps are challenging to attain, we generated synthetic data using graphical rendering from an anatomically realistic 3D colon model and a forward model of a virtual endoscope with alternating light sources. We propose an encoder-decoder style deep network, where the encoder is split into four branches of sub-encoder networks that simultaneously extract features from each of the four sources and fuse these feature maps as the network goes deeper. This is complemented by skip connections, which maintain spatial consistency when the features are decoded. We demonstrate that, when compared to monocular depth estimation, this setup can reduce the average NRMS error for depth estimation in a silicone colon phantom by 38% and in a pig colon by 31%.