Deep Learning Model for Cell Nuclei Segmentation and Lymphocyte Identification in Whole Slide Histology Images

Abstract

Anti-cancer immunotherapy dramatically changes the clinical management of many types of tumours towards less harmful and more personalized treatment plans than conventional chemotherapy or radiation. Precise analysis of the spatial distribution of immune cells in the tumourous tissue is necessary to select patients that would best respond to the treatment. Here, we introduce a deep learning-based workflow for cell nuclei segmentation and subsequent immune cell identification in routine diagnostic images. We applied our workflow on a set of hematoxylin and eosin (H&E) stained breast cancer and colorectal cancer tissue images to detect tumour-infiltrating lymphocytes. Firstly, to segment all nuclei in the tissue, we applied the multiple-image input layer architecture (Micro-Net, Dice coefficient (DC) $0.79\pm 0.02$). We supplemented the Micro-Net with an introduced texture block to increase segmentation accuracy (DC = $0.80\pm 0.02$). We preserved the shallow architecture of the segmentation network with only 280 K trainable parameters (e.g. U-net with ∼1900 K parameters, DC = $0.78\pm 0.03$). Subsequently, we added an active contour layer to the ground truth images to further increase the performance (DC = $0.81\pm 0.02$). Secondly, to discriminate lymphocytes from the set of all segmented nuclei, we explored multilayer perceptron and achieved a 0.70 classification f-score. Remarkably, the binary classification of segmented nuclei was significantly improved (f-score = 0.80) by colour normalization. To inspect model generalization, we have evaluated trained models on a public dataset that was not put to use during training. We conclude that the proposed workflow achieved promising results and, with little effort, can be employed in multi-class nuclei segmentation and identification tasks.