Structure Prediction for Gland Segmentation with Hand-Crafted and Deep Convolutional Features

We present a novel method to segment instances of glandular structures from colon histopathology images. We use a structure learning approach which represents local spatial configurations of class labels, capturing structural information normally ignored by sliding-window methods. This allows us to reveal different spatial structures of pixel labels (e.g., locations between adjacent glands, or far from glands), and to identify correctly neighboring glandular structures as separate instances. Exemplars of label structures are obtained via clustering and used to train support vector machine classifiers. The label structures predicted are then combined and post-processed to obtain segmentation maps. We combine hand-crafted, multi-scale image features with features computed by a deep convolutional network trained to map images to segmentation maps. We evaluate the proposed method on the public domain GlaS data set, which allows extensive comparisons with recent, alternative methods. Using the GlaS contest protocol, our method achieves the overall best performance

Gland segmentation in gastric histology images: detection of intestinal metaplasia

Gastric cancer is one of the most frequent causes of cancer-related deaths worldwide. Gastric intestinal metaplasia (IM) of the mucosa of the stomach has been found to increase the risk of gastric cancer and is considered as one of the precancerous lesions. Therefore, early detection of IM may have a valuable role in histopathological risk assessment regarding the possibility of progression to cancer. Accurate segmentation and analysis of gastric glands from the histological images plays an important role in the diagnostic confirmation of IM. Thus, in this paper, we propose a framework for segmentation of gastric glands and detection of IM. More specifically, we propose the GAGL-Net for the segmentation of glands. Then, based on two features of the extracted glands we classify the tissues into normal and IM cases. The results showed that the proposed gland segmentation approach achieves an F1 score equal to 0.914. Furthermore, the proposed methodology shows great potential for the IM detection achieving an accuracy score equal to 96.6%. To evaluate the efficiency of the proposed methodology we used a publicly available dataset and we created the GAGL dataset consisting of 59 Whole Slide Images (WSI) including both IM and normal cases

Micro-Net: A unified model for segmentation of various objects in microscopy images

Object segmentation and structure localization are important steps in automated image analysis pipelines for microscopy images. We present a convolution neural network (CNN) based deep learning architecture for segmentation of objects in microscopy images. The proposed network can be used to segment cells, nuclei and glands in fluorescence microscopy and histology images after slight tuning of input parameters. The network trains at multiple resolutions of the input image, connects the intermediate layers for better localization and context and generates the output using multi-resolution deconvolution filters. The extra convolutional layers which bypass the max-pooling operation allow the network to train for variable input intensities and object size and make it robust to noisy data. We compare our results on publicly available data sets and show that the proposed network outperforms recent deep learning algorithms

Gland Instance Segmentation in Colon Histology Images

This thesis looks at approaches to gland instance segmentation in histology images. The aim is to find suitable local image representations to describe the gland structures in images with benign tissue and those with malignant tissue and subsequently use them for design of accurate, scalable and flexible gland instance segmentation methods. The gland instance segmentation is a clinically important and technically challenging problem as the morphological structure and visual appearance of gland tissue is highly variable and complex. Glands are one of the most common organs in the human body. The glandular features are present in many cancer types and histopathologists use these features to predict tumour grade. Accurate tumour grading is critical for prescribing suitable cancer treatment resulting in improved outcome and survival rate. Different cancer grades are reflected by differences in glands morphology and structure. It is therefore important to accurately segment glands in histology images in order to get a valid prediction of tumour grade. Several segmentation methods, including segmentation with and without pre-classification, have been proposed and investigated as part of the research reported in this thesis. A number of feature spaces, including hand-crafted and deep features, have been investigated and experimentally validated to find a suitable set of image attributes for representation of benign and malignant gland tissue for the segmentation task. Furthermore, an exhaustive experimental examination of different combinations of features and classification methods have been carried out using both qualitative and quantitative assessments, including detection, shape and area fidelity metrics. It has been shown that the proposed hybrid method combining image level classification, to identify images with benign and malignant tissue, and pixel level classification, to perform gland segmentation, achieved the best results. It has been further shown that modelling benign glands using a three-class model, i.e. inside, outside and gland boundary, and malignant tissue using a two-class model is the best combination for achieving accurate and robust gland instance segmentation results. The deep learning features have been shown to overall outperform handcrafted features, however proposed ring-histogram features still performed adequately, particularly for segmentation of benign glands. The adopted transfer-learning model with proposed image augmentation has proven very successful with 100% image classification accuracy on the available test dataset. It has been shown that the modified object- level Boundary Jaccard metric is more suitable for measuring shape similarity than the previously used object-level Hausdorff distance, as it is not sensitive to outliers and could be easily integrated with region- based metrics such as the object-level Dice index, as contrary to the Hausdorff distance it is bounded between 0 and 1. Dissimilar to most of the other reported research, this study provides comprehensive comparative results for gland segmentation, with a large collection of diverse types of image features, including hand-crafted and deep features. The novel contributions include hybrid segmentation model superimposing image and pixel level classification, data augmentation for re-training deep learning models for the proposed image level classification, and the object- level Boundary Jaccard metric adopted for evaluation of instance segmentation methods

Topology and attention in computational pathology

Histopathology serves as the gold standard in the process of cancer diagnosis and unravelling the disease heterogeneity. In routine practice, a trained histopathologist performs visual examination of tissue glass slides under the microscope. The objective of the visual examination is to observe the morphological appearance of tissue sections, analyse the density of tumour rich areas, spatial arrangement, and architecture of diferent types of cells. However, careful visual examination of tissue slides is a demanding task especially when workloads are high, and the subjective nature of the histological grading inevitably leads to inter- and even intra-observer variability. Attaining high accuracy and objective quantification of tissue specimens in cancer diagnosis are some of the ongoing challenges in modern histopathology. With the recent advent of digital pathology, tissue glass slides can now be scanned with digital slides scanners to produce whole slide images (WSIs). A WSI contains a high-resolution pixel representation of tissue slide, stored in a pyramidal structure and typically containing 1010 pixels. Automated algorithms are generally based on the concepts of digital image analysis which can analyse WSIs to improve the precision and reproducibility in cancer diagnostics. The reliability of the results of an algorithm can be objectively measured and improved against an objective standard. In this thesis, we focus on developing automated methods for quantitative assessment of histology WSIs with the aim of improving the precision and reproducibility of cancer diagnosis. More specifically, the designed automated computational pathology algorithms are based on deep learning models in conjunction with algebraic topology and visual attention mechanisms. To the best of our knowledge, the applicability of attention and topology based methods have not been explored in the domain of computational pathology. In this regard, we propose an algorithm for computing persistent homology profiles (topological features) and propose two variants for effective and reliable tumour segmentation of colorectal cancer WSIs. We show that incorporation of deep features along with topological features improves the overall performance for tumour segmentation. We then present the first-ever systematic study (contest) for scoring the human epidermal growth factor receptor 2 (HER2) biomarker on breast cancer histology WSIs. Further, we devise a reinforcement learning based attention mechanism for HER2 scoring that sequentially identifies and analyses the diagnostically relevant regions within a given image, mimicking the histopathologist who would not usually analyse every part of the slide at the highest magnification. We demonstrate the proposed model outperforms other methods participated in our systematic study, most of them were using state-of-the-art deep convolutional networks. Finally, we propose a multi-task learning framework for simultaneous cell detection and classifi- cation, which we named as Hydra-Net. We then compute an image based biomarker which we refer as digital proximity signature (DPS), to predict overall survival in diffuse large B-cell lymphoma (DLBCL) patients. Our results suggest that patients with high collagen-tumour proximity are likely to experience better overall survival