Search

Weakly-supervised classification of histopathology slides is a computationally intensive task, with a typical whole slide image (WSI) containing billions of pixels to process. We propose Discriminative Region Active Sampling for Multiple Instance Learning (DRAS-MIL), a computationally efficient slide classification method using attention scores to focus sampling on highly discriminative regions. We apply this to the diagnosis of ovarian cancer histological subtypes, which is an essential part of the patient care pathway as different subtypes have different genetic and molecular profiles, treatment options, and patient outcomes. We use a dataset of 714 WSIs acquired from 147 epithelial ovarian cancer patients at Leeds Teaching Hospitals NHS Trust to distinguish the most common subtype, high-grade serous carcinoma, from the other four subtypes (low-grade serous, endometrioid, clear cell, and mucinous carcinomas) combined. We demonstrate that DRAS-MIL can achieve similar classification performance to exhaustive slide analysis, with a 3-fold cross-validated AUC of 0.8679 compared to 0.8781 with standard attention-based MIL classification. Our approach uses at most 18% as much memory as the standard approach, while taking 33% of the time when evaluating on a GPU and only 14% on a CPU alone. Reducing prediction time and memory requirements may benefit clinical deployment and the democratisation of AI, reducing the extent to which computational hardware limits end-user adoption.

This study explores the use of the Dirichlet Variational Autoencoder (DirVAE) for learning disentangled latent representations of chest X-ray (CXR) images. Our working hypothesis is that distributional sparsity, as facilitated by the Dirichlet prior, will encourage disentangled feature learning for the complex task of multi-label classification of CXR images. The DirVAE is trained using CXR images from the CheXpert database, and the predictive capacity of multi-modal latent representations learned by DirVAE models is investigated through implementation of an auxiliary multi-label classification task, with a view to enforce separation of latent factors according to class-specific features. The predictive performance and explainability of the latent space learned using the DirVAE were quantitatively and qualitatively assessed, respectively, and compared with a standard Gaussian prior-VAE (GVAE). We introduce a new approach for explainable multi-label classification in which we conduct gradient-guided latent traversals for each class of interest. Study findings indicate that the DirVAE is able to disentangle latent factors into class-specific visual features, a property not afforded by the GVAE, and achieve a marginal increase in predictive performance relative to GVAE. We generate visual examples to show that our explainability method, when applied to the trained DirVAE, is able to highlight regions in CXR images that are clinically relevant to the class(es) of interest and additionally, can identify cases where classification relies on spurious feature correlations., 13 pages, 8 figures, to be published in SPIE Medical Imaging 2023

Purpose - To characterise and assess the quality of published research evaluating artificial intelligence (AI) methods for ovarian cancer diagnosis or prognosis using histopathology data. Methods - A search of PubMed, Scopus, Web of Science, CENTRAL, and WHO-ICTRP was conducted up to 19/05/2023. The inclusion criteria required that research evaluated AI on histopathology images for diagnostic or prognostic inferences in ovarian cancer. The risk of bias was assessed using PROBAST. Information about each model of interest was tabulated and summary statistics were reported. PRISMA 2020 reporting guidelines were followed. Results - 1573 records were identified, of which 45 were eligible for inclusion. There were 80 models of interest, including 37 diagnostic models, 22 prognostic models, and 21 models with other diagnostically relevant outcomes. Models were developed using 1-1375 slides from 1-776 ovarian cancer patients. Model outcomes included treatment response (11/80), malignancy status (10/80), stain quantity (9/80), and histological subtype (7/80). All models were found to be at high or unclear risk of bias overall, with most research having a high risk of bias in the analysis and a lack of clarity regarding participants and predictors in the study. Research frequently suffered from insufficient reporting and limited validation using small sample sizes. Conclusion - Limited research has been conducted on the application of AI to histopathology images for diagnostic or prognostic purposes in ovarian cancer, and none of the associated models have been demonstrated to be ready for real-world implementation. Key aspects to help ensure clinical translation include more transparent and comprehensive reporting of data provenance and modelling approaches, as well as improved quantitative performance evaluation using cross-validation and external validations.