Segmentation of Pathology Images: A Deep Learning Strategy with Annotated Data

Abstract

Cancer has significantly threatened human life and health for many years. In the clinic, histopathology image segmentation is the golden stand for evaluating the prediction of patient prognosis and treatment outcome. Generally, manually labelling tumour regions in hundreds of high-resolution histopathological images is time-consuming and expensive for pathologists. Recently, the advancements in hardware and computer vision have allowed deep-learning-based methods to become mainstream to segment tumours automatically, significantly reducing the workload of pathologists. However, most current methods rely on large-scale labelled histopathological images. Therefore, this research studies label-effective tumour segmentation methods using deep-learning paradigms to relieve the annotation limitations. Chapter 3 proposes an ensemble framework for fully-supervised tumour segmentation. Usually, the performance of an individual-trained network is limited by significant morphological variances in histopathological images. We propose a fully-supervised learning ensemble fusion model that uses both shallow and deep U-Nets, trained with images of different resolutions and subsets of images, for robust predictions of tumour regions. Noise elimination is achieved with Convolutional Conditional Random Fields. Two open datasets are used to evaluate the proposed method: the ACDC@LungHP challenge at ISBI2019 and the DigestPath challenge at MICCAI2019. With a dice coefficient of 79.7 %, the proposed method takes third place in ACDC@LungHP. In DigestPath 2019, the proposed method achieves a dice coefficient 77.3 %. Well-annotated images are an indispensable part of training fully-supervised segmentation strategies. However, large-scale histopathology images are hardly annotated finely in clinical practice. It is common for labels to be of poor quality or for only a few images to be manually marked by experts. Consequently, fully-supervised methods cannot perform well in these cases. Chapter 4 proposes a self-supervised contrast learning for tumour segmentation. A self-supervised cancer segmentation framework is proposed to reduce label dependency. An innovative contrastive learning scheme is developed to represent tumour features based on unlabelled images. Unlike a normal U-Net, the backbone is a patch-based segmentation network. Additionally, data augmentation and contrastive losses are applied to improve the discriminability of tumour features. A convolutional Conditional Random Field is used to smooth and eliminate noise. Three labelled, and fourteen unlabelled images are collected from a private skin cancer dataset called BSS. Experimental results show that the proposed method achieves better tumour segmentation performance than other popular self-supervised methods. However, by evaluated on the same public dataset as chapter 3, the proposed self-supervised method is hard to handle fine-grained segmentation around tumour boundaries compared to the supervised method we proposed. Chapter 5 proposes a sketch-based weakly-supervised tumour segmentation method. To segment tumour regions precisely with coarse annotations, a sketch-supervised method is proposed, containing a dual CNN-Transformer network and a global normalised class activation map. CNN-Transformer networks simultaneously model global and local tumour features. With the global normalised class activation map, a gradient-based tumour representation can be obtained from the dual network predictions. We invited experts to mark fine and coarse annotations in the private BSS and the public PAIP2019 datasets to facilitate reproducible performance comparisons. Using the BSS dataset, the proposed method achieves 76.686 % IOU and 86.6 % Dice scores, outperforming state-of-the-art methods. Additionally, the proposed method achieves a Dice gain of 8.372 % compared with U-Net on the PAIP2019 dataset. The thesis presents three approaches to segmenting cancers from histology images: fully-supervised, unsupervised, and weakly supervised methods. This research effectively segments tumour regions based on histopathological annotations and well-designed modules. Our studies comprehensively demonstrate label-effective automatic histopathological image segmentation. Experimental results prove that our works achieve state-of-the-art segmentation performances on private and public datasets. In the future, we plan to integrate more tumour feature representation technologies with other medical modalities and apply them to clinical research

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