Katie Allen

Jack Breen, Kieran Zucker, Katie Allen et al.

The rapid growth of digital pathology in recent years has provided an ideal opportunity for the development of artificial intelligence-based tools to improve the accuracy and efficiency of clinical diagnoses. One of the significant roadblocks to current research is the high level of visual variability across digital pathology images, causing models to generalise poorly to unseen data. Stain normalisation aims to standardise the visual profile of digital pathology images without changing the structural content of the images. In this chapter, we explore different techniques which have been used for stain normalisation in digital pathology, with a focus on approaches which utilise generative adversarial networks (GANs). Typically, GAN-based methods outperform non-generative approaches but at the cost of much greater computational requirements. However, it is not clear which method is best for stain normalisation in general, with different GAN and non-GAN approaches outperforming each other in different scenarios and according to different performance metrics. This is an ongoing field of study as researchers aim to identify a method which efficiently and effectively normalises pathology images to make AI models more robust and generalisable.

Jack Breen, Katie Allen, Kieran Zucker et al.

For many patients, current ovarian cancer treatments offer limited clinical benefit. For some therapies, it is not possible to predict patients' responses, potentially exposing them to the adverse effects of treatment without any therapeutic benefit. As part of the automated prediction of treatment effectiveness in ovarian cancer using histopathological images (ATEC23) challenge, we evaluated the effectiveness of deep learning to predict whether a course of treatment including the antiangiogenic drug bevacizumab could contribute to remission or prevent disease progression for at least 6 months in a set of 282 histopathology whole slide images (WSIs) from 78 ovarian cancer patients. Our approach used a pretrained Hierarchical Image Pyramid Transformer (HIPT) to extract region-level features and an attention-based multiple instance learning (ABMIL) model to aggregate features and classify whole slides. The optimal HIPT-ABMIL model had an internal balanced accuracy of 60.2% +- 2.9% and an AUC of 0.646 +- 0.033. Histopathology-specific model pretraining was found to be beneficial to classification performance, though hierarchical transformers were not, with a ResNet feature extractor achieving similar performance. Due to the dataset being small and highly heterogeneous, performance was variable across 5-fold cross-validation folds, and there were some extreme differences between validation and test set performance within folds. The model did not generalise well to tissue microarrays, with accuracy worse than random chance. It is not yet clear whether ovarian cancer WSIs contain information that can be used to accurately predict treatment response, with further validation using larger, higher-quality datasets required.

Jack Breen, Katie Allen, Kieran Zucker et al.

Computer vision models are increasingly capable of classifying ovarian epithelial cancer subtypes, but they differ from pathologists by processing small tissue patches at a single resolution. Multi-resolution graph models leverage the spatial relationships of patches at multiple magnifications, learning the context for each patch. In this study, we conduct the most thorough validation of a graph model for ovarian cancer subtyping to date. Seven models were tuned and trained using five-fold cross-validation on a set of 1864 whole slide images (WSIs) from 434 patients treated at Leeds Teaching Hospitals NHS Trust. The cross-validation models were ensembled and evaluated using a balanced hold-out test set of 100 WSIs from 30 patients, and an external validation set of 80 WSIs from 80 patients in the Transcanadian Study. The best-performing model, a graph model using 10x+20x magnification data, gave balanced accuracies of 73%, 88%, and 99% in cross-validation, hold-out testing, and external validation, respectively. However, this only exceeded the performance of attention-based multiple instance learning in external validation, with a 93% balanced accuracy. Graph models benefitted greatly from using the UNI foundation model rather than an ImageNet-pretrained ResNet50 for feature extraction, with this having a much greater effect on performance than changing the subsequent classification approach. The accuracy of the combined foundation model and multi-resolution graph network offers a step towards the clinical applicability of these models, with a new highest-reported performance for this task, though further validations are still required to ensure the robustness and usability of the models.