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Medical imaging cohorts are often confounded by factors such as acquisition devices, hospital sites, patient backgrounds, and many more. As a result, deep learning models tend to learn spurious correlations instead of causally related features, limiting their generalizability to new and unseen data. This problem can be addressed by minimizing dependence measures between intermediate representations of task-related and non-task-related variables. These measures include mutual information, distance correlation, and the performance of adversarial classifiers. Here, we benchmark such dependence measures for the task of preventing shortcut learning. We study a simplified setting using Morpho-MNIST and a medical imaging task with CheXpert chest radiographs. Our results provide insights into how to mitigate confounding factors in medical imaging., Comment: Accepted to the 15th International Workshop on Machine Learning in Medical Imaging (MLMI 2024); new version: appendix moved to the end, after the references

Recent works have introduced methods to estimate segmentation performance without ground truth, relying solely on neural network softmax outputs. These techniques hold potential for intuitive output quality control. However, such performance estimates rely on calibrated softmax outputs, which is often not the case in modern neural networks. Moreover, the estimates do not take into account inherent uncertainty in segmentation tasks. These limitations may render precise performance predictions unattainable, restricting the practical applicability of performance estimation methods. To address these challenges, we develop a novel approach for predicting performance ranges with statistical guarantees of containing the ground truth with a user specified probability. Our method leverages sampling-based segmentation uncertainty estimation to derive heuristic performance ranges, and applies split conformal prediction to transform these estimates into rigorous prediction ranges that meet the desired guarantees. We demonstrate our approach on the FIVES retinal vessel segmentation dataset and compare five commonly used sampling-based uncertainty estimation techniques. Our results show that it is possible to achieve the desired coverage with small prediction ranges, highlighting the potential of performance range prediction as a valuable tool for output quality control., Comment: Accepted as an oral presentation at MICCAI UNSURE 2024

Interpretability is crucial for machine learning algorithms in high-stakes medical applications. However, high-performing neural networks typically cannot explain their predictions. Post-hoc explanation methods provide a way to understand neural networks but have been shown to suffer from conceptual problems. Moreover, current research largely focuses on providing local explanations for individual samples rather than global explanations for the model itself. In this paper, we propose Attri-Net, an inherently interpretable model for multi-label classification that provides local and global explanations. Attri-Net first counterfactually generates class-specific attribution maps to highlight the disease evidence, then performs classification with logistic regression classifiers based solely on the attribution maps. Local explanations for each prediction can be obtained by interpreting the attribution maps weighted by the classifiers' weights. Global explanation of whole model can be obtained by jointly considering learned average representations of the attribution maps for each class (called the class centers) and the weights of the linear classifiers. To ensure the model is ``right for the right reason", we further introduce a mechanism to guide the model's explanations to align with human knowledge. Our comprehensive evaluations show that Attri-Net can generate high-quality explanations consistent with clinical knowledge while not sacrificing classification performance., Comment: Extension of paper: Inherently Interpretable Multi-Label Classification Using Class-Specific Counterfactuals (Sun et al., MIDL 2023)

Retinal fundus images play a crucial role in the early detection of eye diseases. However, the impact of technical factors on these images can pose challenges for reliable AI applications in ophthalmology. For example, large fundus cohorts are often confounded by factors like camera type, bearing the risk of learning shortcuts rather than the causal relationships behind the image generation process. Here, we introduce a population model for retinal fundus images that effectively disentangles patient attributes from camera effects, enabling controllable and highly realistic image generation. To achieve this, we propose a disentanglement loss based on distance correlation. Through qualitative and quantitative analyses, we show that our models encode desired information in disentangled subspaces and enable controllable image generation based on the learned subspaces, demonstrating the effectiveness of our disentanglement loss. The project's code is publicly available: https://github.com/berenslab/disentangling-retinal-images.

While deep neural network models offer unmatched classification performance, they are prone to learning spurious correlations in the data. Such dependencies on confounding information can be difficult to detect using performance metrics if the test data comes from the same distribution as the training data. Interpretable ML methods such as post-hoc explanations or inherently interpretable classifiers promise to identify faulty model reasoning. However, there is mixed evidence whether many of these techniques are actually able to do so. In this paper, we propose a rigorous evaluation strategy to assess an explanation technique's ability to correctly identify spurious correlations. Using this strategy, we evaluate five post-hoc explanation techniques and one inherently interpretable method for their ability to detect three types of artificially added confounders in a chest x-ray diagnosis task. We find that the post-hoc technique SHAP, as well as the inherently interpretable Attri-Net provide the best performance and can be used to reliably identify faulty model behavior., Comment: Accepted to MICCAI 2023

Distribution shifts remain a fundamental problem for the safe application of machine learning systems. If undetected, they may impact the real-world performance of such systems or will at least render original performance claims invalid. In this paper, we focus on the detection of subgroup shifts, a type of distribution shift that can occur when subgroups have a different prevalence during validation compared to the deployment setting. For example, algorithms developed on data from various acquisition settings may be predominantly applied in hospitals with lower quality data acquisition, leading to an inadvertent performance drop. We formulate subgroup shift detection in the framework of statistical hypothesis testing and show that recent state-of-the-art statistical tests can be effectively applied to subgroup shift detection on medical imaging data. We provide synthetic experiments as well as extensive evaluation on clinically meaningful subgroup shifts on histopathology as well as retinal fundus images. We conclude that classifier-based subgroup shift detection tests could be a particularly useful tool for post-market surveillance of deployed ML systems., Comment: Under review

Interpretability is essential for machine learning algorithms in high-stakes application fields such as medical image analysis. However, high-performing black-box neural networks do not provide explanations for their predictions, which can lead to mistrust and suboptimal human-ML collaboration. Post-hoc explanation techniques, which are widely used in practice, have been shown to suffer from severe conceptual problems. Furthermore, as we show in this paper, current explanation techniques do not perform adequately in the multi-label scenario, in which multiple medical findings may co-occur in a single image. We propose Attri-Net, an inherently interpretable model for multi-label classification. Attri-Net is a powerful classifier that provides transparent, trustworthy, and human-understandable explanations. The model first generates class-specific attribution maps based on counterfactuals to identify which image regions correspond to certain medical findings. Then a simple logistic regression classifier is used to make predictions based solely on these attribution maps. We compare Attri-Net to five post-hoc explanation techniques and one inherently interpretable classifier on three chest X-ray datasets. We find that Attri-Net produces high-quality multi-label explanations consistent with clinical knowledge and has comparable classification performance to state-of-the-art classification models., Comment: Accepted to MIDL 2023

Surface reconstruction is a vital tool in a wide range of areas of medical image analysis and clinical research. Despite the fact that many methods have proposed solutions to the reconstruction problem, most, due to their deterministic nature, do not directly address the issue of quantifying uncertainty associated with their predictions. We remedy this by proposing a novel probabilistic deep learning approach capable of simultaneous surface reconstruction and associated uncertainty prediction. The method incorporates prior shape information in the form of a principal component analysis (PCA) model. Experiments using the UK Biobank data show that our probabilistic approach outperforms an analogous deterministic PCA-based method in the task of 2D organ delineation and quantifies uncertainty by formulating distributions over predicted surface vertex positions., Comment: Accepted to ShapeMI MICCAI 2018: Workshop on Shape in Medical Imaging

Semantic segmentation of medical images is a crucial step for the quantification of healthy anatomy and diseases alike. The majority of the current state-of-the-art segmentation algorithms are based on deep neural networks and rely on large datasets with full pixel-wise annotations. Producing such annotations can often only be done by medical professionals and requires large amounts of valuable time. Training a medical image segmentation network with weak annotations remains a relatively unexplored topic. In this work we investigate training strategies to learn the parameters of a pixel-wise segmentation network from scribble annotations alone. We evaluate the techniques on public cardiac (ACDC) and prostate (NCI-ISBI) segmentation datasets. We find that the networks trained on scribbles suffer from a remarkably small degradation in Dice of only 2.9% (cardiac) and 4.5% (prostate) with respect to a network trained on full annotations., Comment: Accepted for presentation at DLMIA 2018

Attributing the pixels of an input image to a certain category is an important and well-studied problem in computer vision, with applications ranging from weakly supervised localisation to understanding hidden effects in the data. In recent years, approaches based on interpreting a previously trained neural network classifier have become the de facto state-of-the-art and are commonly used on medical as well as natural image datasets. In this paper, we discuss a limitation of these approaches which may lead to only a subset of the category specific features being detected. To address this problem we develop a novel feature attribution technique based on Wasserstein Generative Adversarial Networks (WGAN), which does not suffer from this limitation. We show that our proposed method performs substantially better than the state-of-the-art for visual attribution on a synthetic dataset and on real 3D neuroimaging data from patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). For AD patients the method produces compellingly realistic disease effect maps which are very close to the observed effects., Comment: Accepted to CVPR 2018

Accurate segmentation of the heart is an important step towards evaluating cardiac function. In this paper, we present a fully automated framework for segmentation of the left (LV) and right (RV) ventricular cavities and the myocardium (Myo) on short-axis cardiac MR images. We investigate various 2D and 3D convolutional neural network architectures for this task. We investigate the suitability of various state-of-the art 2D and 3D convolutional neural network architectures, as well as slight modifications thereof, for this task. Experiments were performed on the ACDC 2017 challenge training dataset comprising cardiac MR images of 100 patients, where manual reference segmentations were made available for end-diastolic (ED) and end-systolic (ES) frames. We find that processing the images in a slice-by-slice fashion using 2D networks is beneficial due to a relatively large slice thickness. However, the exact network architecture only plays a minor role. We report mean Dice coefficients of $0.950$ (LV), $0.893$ (RV), and $0.899$ (Myo), respectively with an average evaluation time of 1.1 seconds per volume on a modern GPU., Comment: to appear in STACOM 2017 proceedings

To efficiently establish training databases for machine learning methods, collaborative and crowdsourcing platforms have been investigated to collectively tackle the annotation effort. However, when this concept is ported to the medical imaging domain, reading expertise will have a direct impact on the annotation accuracy. In this study, we examine the impact of expertise and the amount of available annotations on the accuracy outcome of a liver segmentation problem in an abdominal computed tomography (CT) image database. In controlled experiments, we study this impact for different types of weak annotations. To address the decrease in accuracy associated with lower expertise, we propose a method for outlier correction making use of a weakly labelled atlas. Using this approach, we demonstrate that weak annotations subject to high error rates can achieve a similarly high accuracy as state-of-the-art multi-atlas segmentation approaches relying on a large amount of expert manual segmentations. Annotations of this nature can realistically be obtained from a non-expert crowd and can potentially enable crowdsourcing of weak annotation tasks for medical image analysis.

Identifying and interpreting fetal standard scan planes during 2D ultrasound mid-pregnancy examinations are highly complex tasks which require years of training. Apart from guiding the probe to the correct location, it can be equally difficult for a non-expert to identify relevant structures within the image. Automatic image processing can provide tools to help experienced as well as inexperienced operators with these tasks. In this paper, we propose a novel method based on convolutional neural networks which can automatically detect 13 fetal standard views in freehand 2D ultrasound data as well as provide a localisation of the fetal structures via a bounding box. An important contribution is that the network learns to localise the target anatomy using weak supervision based on image-level labels only. The network architecture is designed to operate in real-time while providing optimal output for the localisation task. We present results for real-time annotation, retrospective frame retrieval from saved videos, and localisation on a very large and challenging dataset consisting of images and video recordings of full clinical anomaly screenings. We found that the proposed method achieved an average F1-score of 0.798 in a realistic classification experiment modelling real-time detection, and obtained a 90.09% accuracy for retrospective frame retrieval. Moreover, an accuracy of 77.8% was achieved on the localisation task., Comment: 12 pages, 8 figures, published in IEEE Transactions in Medical Imaging

Multi-atlas segmentation is a widely used tool in medical image analysis, providing robust and accurate results by learning from annotated atlas datasets. However, the availability of fully annotated atlas images for training is limited due to the time required for the labelling task. Segmentation methods requiring only a proportion of each atlas image to be labelled could therefore reduce the workload on expert raters tasked with annotating atlas images. To address this issue, we first re-examine the labelling problem common in many existing approaches and formulate its solution in terms of a Markov Random Field energy minimisation problem on a graph connecting atlases and the target image. This provides a unifying framework for multi-atlas segmentation. We then show how modifications in the graph configuration of the proposed framework enable the use of partially annotated atlas images and investigate different partial annotation strategies. The proposed method was evaluated on two Magnetic Resonance Imaging (MRI) datasets for hippocampal and cardiac segmentation. Experiments were performed aimed at (1) recreating existing segmentation techniques with the proposed framework and (2) demonstrating the potential of employing sparsely annotated atlas data for multi-atlas segmentation.