Milda Pocevičiūtė

Milda Pocevičiūtė, Gabriel Eilertsen, Stina Garvin et al.

Multiple-instance learning (MIL) is an attractive approach for digital pathology applications as it reduces the costs related to data collection and labelling. However, it is not clear how sensitive MIL is to clinically realistic domain shifts, i.e., differences in data distribution that could negatively affect performance, and if already existing metrics for detecting domain shifts work well with these algorithms. We trained an attention-based MIL algorithm to classify whether a whole-slide image of a lymph node contains breast tumour metastases. The algorithm was evaluated on data from a hospital in a different country and various subsets of this data that correspond to different levels of domain shift. Our contributions include showing that MIL for digital pathology is affected by clinically realistic differences in data, evaluating which features from a MIL model are most suitable for detecting changes in performance, and proposing an unsupervised metric named Fréchet Domain Distance (FDD) for quantification of domain shifts. Shift measure performance was evaluated through the mean Pearson correlation to change in classification performance, where FDD achieved 0.70 on 10-fold cross-validation models. The baselines included Deep ensemble, Difference of Confidence, and Representation shift which resulted in 0.45, -0.29, and 0.56 mean Pearson correlation, respectively. FDD could be a valuable tool for care providers and vendors who need to verify if a MIL system is likely to perform reliably when implemented at a new site, without requiring any additional annotations from pathologists.

Misgina Tsighe Hagos, Antti Suutala, Dmitrii Bychkov et al.

Deep learning based cervical cancer classification can potentially increase access to screening in low-resource regions. However, deep learning models are often overconfident and do not reliably reflect diagnostic uncertainty. Moreover, they are typically optimized to generate maximum-likelihood predictions, which fail to convey uncertainty or ambiguity in their results. Such challenges can be addressed using conformal prediction, a model-agnostic framework for generating prediction sets that contain likely classes for trained deep-learning models. The size of these prediction sets indicates model uncertainty, contracting as model confidence increases. However, existing conformal prediction evaluation primarily focuses on whether the prediction set includes or covers the true class, often overlooking the presence of extraneous classes. We argue that prediction sets should be truthful and valuable to end users, ensuring that the listed likely classes align with human expectations rather than being overly relaxed and including false positives or unlikely classes. In this study, we comprehensively validate conformal prediction sets using expert annotation sets collected from multiple annotators. We evaluate three conformal prediction approaches applied to three deep-learning models trained for cervical atypia classification. Our expert annotation-based analysis reveals that conventional coverage-based evaluations overestimate performance and that current conformal prediction methods often produce prediction sets that are not well aligned with human labels. Additionally, we explore the capabilities of the conformal prediction methods in identifying ambiguous and out-of-distribution data.

Milda Pocevičiūtė, Gabriel Eilertsen, Sofia Jarkman et al.

Deep learning (DL) has shown great potential in digital pathology applications. The robustness of a diagnostic DL-based solution is essential for safe clinical deployment. In this work we evaluate if adding uncertainty estimates for DL predictions in digital pathology could result in increased value for the clinical applications, by boosting the general predictive performance or by detecting mispredictions. We compare the effectiveness of model-integrated methods (MC dropout and Deep ensembles) with a model-agnostic approach (Test time augmentation, TTA). Moreover, four uncertainty metrics are compared. Our experiments focus on two domain shift scenarios: a shift to a different medical center and to an underrepresented subtype of cancer. Our results show that uncertainty estimates increase reliability by reducing a model's sensitivity to classification threshold selection as well as by detecting between 70\% and 90\% of the mispredictions done by the model. Overall, the deep ensembles method achieved the best performance closely followed by TTA.

Milda Pocevičiūtė, Gabriel Eilertsen, Claes Lundström

Machine learning (ML) algorithms are optimized for the distribution represented by the training data. For outlier data, they often deliver predictions with equal confidence, even though these should not be trusted. In order to deploy ML-based digital pathology solutions in clinical practice, effective methods for detecting anomalous data are crucial to avoid incorrect decisions in the outlier scenario. We propose a new unsupervised learning approach for anomaly detection in histopathology data based on generative adversarial networks (GANs). Compared to the existing GAN-based methods that have been used in medical imaging, the proposed approach improves significantly on performance for pathology data. Our results indicate that histopathology imagery is substantially more complex than the data targeted by the previous methods. This complexity requires not only a more advanced GAN architecture but also an appropriate anomaly metric to capture the quality of the reconstructed images.