Jeroen Veltman

Shreyasi Pathak, Jörg Schlötterer, Jeroen Geerdink et al.

Breast cancer prediction models for mammography assume that annotations are available for individual images or regions of interest (ROIs), and that there is a fixed number of images per patient. These assumptions do not hold in real hospital settings, where clinicians provide only a final diagnosis for the entire mammography exam (case). Since data in real hospital settings scales with continuous patient intake, while manual annotation efforts do not, we develop a framework for case-level breast cancer prediction that does not require any manual annotation and can be trained with case labels readily available at the hospital. Specifically, we propose a two-level multi-instance learning (MIL) approach at patch and image level for case-level breast cancer prediction and evaluate it on two public and one private dataset. We propose a novel domain-specific MIL pooling observing that breast cancer may or may not occur in both sides, while images of both breasts are taken as a precaution during mammography. We propose a dynamic training procedure for training our MIL framework on a variable number of images per case. We show that our two-level MIL model can be applied in real hospital settings where only case labels, and a variable number of images per case are available, without any loss in performance compared to models trained on image labels. Only trained with weak (case-level) labels, it has the capability to point out in which breast side, mammography view and view region the abnormality lies.

Shreyasi Pathak, Jörg Schlötterer, Jeroen Veltman et al.

Deep learning models have achieved high performance in medical applications, however, their adoption in clinical practice is hindered due to their black-box nature. Self-explainable models, like prototype-based models, can be especially beneficial as they are interpretable by design. However, if the learnt prototypes are of low quality then the prototype-based models are as good as black-box. Having high quality prototypes is a pre-requisite for a truly interpretable model. In this work, we propose a prototype evaluation framework for coherence (PEF-C) for quantitatively evaluating the quality of the prototypes based on domain knowledge. We show the use of PEF-C in the context of breast cancer prediction using mammography. Existing works on prototype-based models on breast cancer prediction using mammography have focused on improving the classification performance of prototype-based models compared to black-box models and have evaluated prototype quality through anecdotal evidence. We are the first to go beyond anecdotal evidence and evaluate the quality of the mammography prototypes systematically using our PEF-C. Specifically, we apply three state-of-the-art prototype-based models, ProtoPNet, BRAIxProtoPNet++ and PIP-Net on mammography images for breast cancer prediction and evaluate these models w.r.t. i) classification performance, and ii) quality of the prototypes, on three public datasets. Our results show that prototype-based models are competitive with black-box models in terms of classification performance, and achieve a higher score in detecting ROIs. However, the quality of the prototypes are not yet sufficient and can be improved in aspects of relevance, purity and learning a variety of prototypes. We call the XAI community to systematically evaluate the quality of the prototypes to check their true usability in high stake decisions and improve such models further.

Anindo Saha, Joeran S. Bosma, Jasper J. Twilt et al.

In this intercontinental, confirmatory study, we include a retrospective cohort of 22,481 MRI examinations (21,288 patients; 46 cities in 22 countries) to train and externally validate the PI-CAI-2B model, i.e., an efficient, next-generation iteration of the state-of-the-art AI system that was developed for detecting Gleason grade group $\geq$2 prostate cancer on MRI during the PI-CAI study. Of these examinations, 20,471 cases (19,278 patients; 26 cities in 14 countries) from two EU Horizon projects (ProCAncer-I, COMFORT) and 12 independent centers based in Europe, North America, Asia and Africa, are used for training and internal testing. Additionally, 2010 cases (2010 patients; 20 external cities in 12 countries) from population-based screening (STHLM3-MRI, IP1-PROSTAGRAM trials) and primary diagnostic settings (PRIME trial) based in Europe, North and South Americas, Asia and Australia, are used for external testing. Primary endpoint is the proportion of AI-based assessments in agreement with the standard of care diagnoses (i.e., clinical assessments made by expert uropathologists on histopathology, if available, or at least two expert urogenital radiologists in consensus; with access to patient history and peer consultation) in the detection of Gleason grade group $\geq$2 prostate cancer within the external testing cohorts. Our statistical analysis plan is prespecified with a hypothesis of diagnostic interchangeability to the standard of care at the PI-RADS $\geq$3 (primary diagnosis) or $\geq$4 (screening) cut-off, considering an absolute margin of 0.05 and reader estimates derived from the PI-CAI observer study (62 radiologists reading 400 cases). Secondary measures comprise the area under the receiver operating characteristic curve (AUROC) of the AI system stratified by imaging quality, patient age and patient ethnicity to identify underlying biases (if any).