Prototype-based Interpretable Breast Cancer Prediction Models:Analysis and Challenges

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

Prototype-Based Interpretable Breast Cancer Prediction Models:Analysis and Challenges

Deep learning models have achieved high performance in medical applications, however, their adoption in clinical practice is hindered due to their black-box nature. Using explainable AI (XAI) in high-stake medical decisions could increase their usability in clinical settings. 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-Coh) for quantitatively evaluating the quality of the prototypes based on domain knowledge. We show the use of PEF-Coh 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-Coh. 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.</p

Case-level Breast Cancer Prediction for Real Hospital Settings

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

Accurate and Reliable Classification of Unstructured Reports on Their Diagnostic Goal Using BERT Models

Understanding the diagnostic goal of medical reports is valuable information for understanding patient flows. This work focuses on extracting the reason for taking an MRI scan of Multiple Sclerosis (MS) patients using the attached free-form reports: Diagnosis, Progression or Monitoring. We investigate the performance of domain-dependent and general state-of-the-art language models and their alignment with domain expertise. To this end, eXplainable Artificial Intelligence (XAI) techniques are used to acquire insight into the inner workings of the model, which are verified on their trustworthiness. The verified XAI explanations are then compared with explanations from a domain expert, to indirectly determine the reliability of the model. BERTje, a Dutch Bidirectional Encoder Representations from Transformers (BERT) model, outperforms RobBERT and MedRoBERTa.nl in both accuracy and reliability. The latter model (MedRoBERTa.nl) is a domain-specific model, while BERTje is a generic model, showing that domain-specific models are not always superior. Our validation of BERTje in a small prospective study shows promising results for the potential uptake of the model in a practical setting.</p

Accurate and Reliable Classification of Unstructured Reports on Their Diagnostic Goal Using BERT Models

Understanding the diagnostic goal of medical reports is valuable information for understanding patient flows. This work focuses on extracting the reason for taking an MRI scan of Multiple Sclerosis (MS) patients using the attached free-form reports: Diagnosis, Progression or Monitoring. We investigate the performance of domain-dependent and general state-of-the-art language models and their alignment with domain expertise. To this end, eXplainable Artificial Intelligence (XAI) techniques are used to acquire insight into the inner workings of the model, which are verified on their trustworthiness. The verified XAI explanations are then compared with explanations from a domain expert, to indirectly determine the reliability of the model. BERTje, a Dutch Bidirectional Encoder Representations from Transformers (BERT) model, outperforms RobBERT and MedRoBERTa.nl in both accuracy and reliability. The latter model (MedRoBERTa.nl) is a domain-specific model, while BERTje is a generic model, showing that domain-specific models are not always superior. Our validation of BERTje in a small prospective study shows promising results for the potential uptake of the model in a practical setting.</p

Interpreting and Correcting Medical Image Classification with PIP-Net

Part-prototype models are explainable-by-design image classifiers, and a promising alternative to black box AI. This paper explores the applicability and potential of interpretable machine learning, in particular PIP-Net, for automated diagnosis support on real-world medical imaging data. PIP-Net learns human-understandable prototypical image parts and we evaluate its accuracy and interpretability for fracture detection and skin cancer diagnosis. We find that PIP-Net's decision making process is in line with medical classification standards, while only provided with image-level class labels. Because of PIP-Net's unsupervised pretraining of prototypes, data quality problems such as undesired text in an X-ray or labelling errors can be easily identified. Additionally, we are the first to show that humans can manually correct the reasoning of PIP-Net by directly disabling undesired prototypes. We conclude that part-prototype models are promising for medical applications due to their interpretability and potential for advanced model debugging

Interpreting and Correcting Medical Image Classification with PIP-Net

Part-prototype models are explainable-by-design image classifiers, and a promising alternative to black box AI. This paper explores the applicability and potential of interpretable machine learning, in particular PIP-Net, for automated diagnosis support on real-world medical imaging data. PIP-Net learns human-understandable prototypical image parts and we evaluate its accuracy and interpretability for fracture detection and skin cancer diagnosis. We find that PIP-Net’s decision making process is in line with medical classification standards, while only provided with image-level class labels. Because of PIP-Net’s unsupervised pretraining of prototypes, data quality problems such as undesired text in an X-ray or labelling errors can be easily identified. Additionally, we are the first to show that humans can manually correct the reasoning of PIP-Net by directly disabling undesired prototypes. We conclude that part-prototype models are promising for medical applications due to their interpretability and potential for advanced model debugging.</p

Feature importance to explain multimodal prediction models. A clinical use case

Surgery to treat elderly hip fracture patients may cause complications that can lead to early mortality. An early warning system for complications could provoke clinicians to monitor high-risk patients more carefully and address potential complications early, or inform the patient. In this work, we develop a multimodal deep-learning model for post-operative mortality prediction using pre-operative and per-operative data from elderly hip fracture patients. Specifically, we include static patient data, hip and chest images before surgery in pre-operative data, vital signals, and medications administered during surgery in per-operative data. We extract features from image modalities using ResNet and from vital signals using LSTM. Explainable model outcomes are essential for clinical applicability, therefore we compute Shapley values to explain the predictions of our multimodal black box model. We find that i) Shapley values can be used to estimate the relative contribution of each modality both locally and globally, and ii) a modified version of the chain rule can be used to propagate Shapley values through a sequence of models supporting interpretable local explanations. Our findings imply that a multimodal combination of black box models can be explained by propagating Shapley values through the model sequence