A Survey on Cell Nuclei Instance Segmentation and Classification: Leveraging Context and Attention

Manually annotating nuclei from the gigapixel Hematoxylin and Eosin (H&E)-stained Whole Slide Images (WSIs) is a laborious and costly task, meaning automated algorithms for cell nuclei instance segmentation and classification could alleviate the workload of pathologists and clinical researchers and at the same time facilitate the automatic extraction of clinically interpretable features. But due to high intra- and inter-class variability of nuclei morphological and chromatic features, as well as H&E-stains susceptibility to artefacts, state-of-the-art algorithms cannot correctly detect and classify instances with the necessary performance. In this work, we hypothesise context and attention inductive biases in artificial neural networks (ANNs) could increase the generalization of algorithms for cell nuclei instance segmentation and classification. We conduct a thorough survey on context and attention methods for cell nuclei instance segmentation and classification from H&E-stained microscopy imaging, while providing a comprehensive discussion of the challenges being tackled with context and attention. Besides, we illustrate some limitations of current approaches and present ideas for future research. As a case study, we extend both a general instance segmentation and classification method (Mask-RCNN) and a tailored cell nuclei instance segmentation and classification model (HoVer-Net) with context- and attention-based mechanisms, and do a comparative analysis on a multi-centre colon nuclei identification and counting dataset. Although pathologists rely on context at multiple levels while paying attention to specific Regions of Interest (RoIs) when analysing and annotating WSIs, our findings suggest translating that domain knowledge into algorithm design is no trivial task, but to fully exploit these mechanisms, the scientific understanding of these methods should be addressed.