HEROHE Challenge: Predicting HER2 Status in Breast Cancer from Hematoxylin–Eosin Whole-Slide Imaging

Breast cancer is the most common malignancy in women worldwide, and is responsible for more than half a million deaths each year. The appropriate therapy depends on the evaluation of the expression of various biomarkers, such as the human epidermal growth factor receptor 2 (HER2) transmembrane protein, through specialized techniques, such as immunohistochemistry or in situ hybridization. In this work, we present the HER2 on hematoxylin and eosin (HEROHE) challenge, a parallel event of the 16th European Congress on Digital Pathology, which aimed to predict the HER2 status in breast cancer based only on hematoxylin–eosin-stained tissue samples, thus avoiding specialized techniques. The challenge consisted of a large, annotated, whole-slide images dataset (509), specifically collected for the challenge. Models for predicting HER2 status were presented by 21 teams worldwide. The best-performing models are presented by detailing the network architectures and key parameters. Methods are compared and approaches, core methodologies, and software choices contrasted. Different evaluation metrics are discussed, as well as the performance of the presented models for each of these metrics. Potential differences in ranking that would result from different choices of evaluation metrics highlight the need for careful consideration at the time of their selection, as the results show that some metrics may misrepresent the true potential of a model to solve the problem for which it was developed. The HEROHE dataset remains publicly available to promote advances in the field of computational pathology

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

An Aggregation of Aggregation Methods in Computational Pathology

Image analysis and machine learning algorithms operating on multi-gigapixel whole-slide images (WSIs) often process a large number of tiles (sub-images) and require aggregating predictions from the tiles in order to predict WSI-level labels. In this paper, we present a review of existing literature on various types of aggregation methods with a view to help guide future research in the area of computational pathology (CPath). We propose a general CPath workflow with three pathways that consider multiple levels and types of data and the nature of computation to analyse WSIs for predictive modelling. We categorize aggregation methods according to the context and representation of the data, features of computational modules and CPath use cases. We compare and contrast different methods based on the principle of multiple instance learning, perhaps the most commonly used aggregation method, covering a wide range of CPath literature. To provide a fair comparison, we consider a specific WSI-level prediction task and compare various aggregation methods for that task. Finally, we conclude with a list of objectives and desirable attributes of aggregation methods in general, pros and cons of the various approaches, some recommendations and possible future directions.Comment: 32 pages, 4 figure

Histopathological image analysis for breast cancer diagnosis by ensembles of convolutional neural networks and genetic algorithms

One of the most invasive cancer types which affect women is breast cancer. Unfortunately, it exhibits a high mortality rate. Automated histopathological image analysis can help to diagnose the disease. Therefore, computer aided diagnosis by intelligent image analysis can help in the diagnosis tasks associated with this disease. Here we propose an automated system for histopathological image analysis that is based on deep learning neural networks with convolutional layers. Rather than a single network, an ensemble of them is built so as to attain higher recognition rates, which are obtained by computing a consensus decision from the individual networks of the ensemble. A final step involves the optimization of the set of networks that are included in the ensemble by a genetic algorithm. Experimental results are provided with a set of benchmark images, with favorable outcomes.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech