The widespread adoption of whole slide imaging has increased the demand for effective and efficient gigapixel image analysis. Deep learning is at the forefront of computer vision, showcasing significant improvements over previous methodologies on visual understanding. However, whole slide images have billions of pixels and suffer from high morphological heterogeneity as well as from different types of artefacts. Collectively, these impede the conventional use of deep learning. For the clinical translation of deep learning solutions to become a reality, these challenges need to be addressed. In this paper, we review work on the interdisciplinary attempt of training deep neural networks using whole slide images, and highlight the different ideas underlying these methodologies.Recently, NHS Greater Glasgow and Clyde, one of the largest single site pathology services in Europe, has begun proceedings to undergo full digitization. As the adoption of digital pathology becomes wider, automated image analysis of tissue morphology has the potential to further establish itself in pathology and ultimately decrease the workload of pathologists, reduce turnaround times for reporting, and standardise clinical practices. For example, known or novel biomarkers and histopathological features can be automatically quantified [22,23,26,8,11,3,36,40,20]. Furthermore, deep learning techniques can be employed to recognize morphological patterns within the specimen for diagnostic and triaging purposes [38,48,32,50].
Accurate prognosis is fundamental in planning an appropriate therapy for cancer patients. Consequent to the heterogeneity of the disease, intra- and inter-pathologist variability, and the inherent limitations of current pathological reporting systems, patient outcome varies considerably within similarly staged patient cohorts. This is particularly true when classifying stage II colorectal cancer patients using the current TNM guidelines. The aim of the present work is to address this problem through the use of machine learning. In particular, we introduce a data driven framework which makes use of a large number of diverse types of features, readily collected from immunofluorescence imagery. Its outstanding performance in predicting mortality in stage II patients (AUROC = 0:94), exceeds that of current clinical guidelines such as pT stage (AUROC = 0:65), and is demonstrated on a cohort of 173 colorectal cancer patients.
Digital pathology (DP) is a new research area which falls under the broad umbrella of health informatics. Owing to its potential for major public health impact, in recent years DP has been attracting much research attention. Nevertheless, a wide breadth of significant conceptual and technical challenges remain, few of them greater than those encountered in the field of oncology. The automatic analysis of digital pathology slides of cancerous tissues is particularly problematic due to the inherent heterogeneity of the disease, extremely large images, amongst numerous others. In this paper we introduce a novel machine learning based framework for the prediction of colorectal cancer outcome from whole digitized haematoxylin & eosin (H&E) stained histopathology slides. Using a real-world data set we demonstrate the effectiveness of the method and present a detailed analysis of its different elements which corroborate its ability to extract and learn salient, discriminative, and clinically meaningful content.
The clinical staging and prognosis of muscle-invasive bladder cancer (MIBC) routinely includes the assessment of patient tissue samples by a pathologist. Recent studies corroborate the importance of image analysis in identifying and quantifying immunological markers from tissue samples that can provide further insight into patient prognosis. In this paper, we apply multiplex immunofluorescence to MIBC tissue sections to capture whole-slide images and quantify potential prognostic markers related to lymphocytes, macrophages, tumour buds, and PD-L1. We propose a machine-learning-based approach for the prediction of 5 year prognosis with different combinations of image, clinical, and spatial features. An ensemble model comprising several functionally different models successfully stratifies MIBC patients into two risk groups with high statistical significance (p value < 1×10−5). Critical to improving MIBC survival rates, our method correctly classifies 71.4% of the patients who succumb to MIBC, which is significantly more than the 28.6% of the current clinical gold standard, the TNM staging system.
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