Esther Puyol-Antón

Yiyang Xu, Hao Xu, Matthew Sinclair et al.

Cardiac magnetic resonance (CMR) imaging and computed tomography (CT) are two common non-invasive imaging methods for assessing patients with cardiovascular disease. CMR typically acquires multiple sparse 2D slices, with unavoidable respiratory motion artefacts between slices, whereas CT acquires isotropic dense data but uses ionising radiation. In this study, we explore the combination of Slice Shifting Algorithm (SSA), Spatial Transformer Network (STN), and Label Transformer Network (LTN) to: 1) correct respiratory motion between segmented slices, and 2) transform sparse segmentation data into dense segmentation. All combinations were validated using synthetic motion-corrupted CMR slice segmentation generated from CT in 1699 cases, where the dense CT serves as the ground truth. In 199 testing cases, SSA-LTN achieved the best results for Dice score and Huasdorff distance (94.0% and 4.7 mm respectively, average over 5 labels) but gave topological errors in 8 cases. STN was effective as a plug-in tool for correcting all topological errors with minimal impact on overall performance (93.5% and 5.0 mm respectively). SSA also proves to be a valuable plug-in tool, enhancing performance over both STN-based and LTN-based models. The code for these different combinations is available at https://github.com/XESchong/STACOM2024.

Cosmin I. Bercea, Esther Puyol-Antón, Benedikt Wiestler et al.

Unsupervised anomaly detection methods offer a promising and flexible alternative to supervised approaches, holding the potential to revolutionize medical scan analysis and enhance diagnostic performance. In the current landscape, it is commonly assumed that differences between a test case and the training distribution are attributed solely to pathological conditions, implying that any disparity indicates an anomaly. However, the presence of other potential sources of distributional shift, including scanner, age, sex, or race, is frequently overlooked. These shifts can significantly impact the accuracy of the anomaly detection task. Prominent instances of such failures have sparked concerns regarding the bias, credibility, and fairness of anomaly detection. This work presents a novel analysis of biases in unsupervised anomaly detection. By examining potential non-pathological distributional shifts between the training and testing distributions, we shed light on the extent of these biases and their influence on anomaly detection results. Moreover, this study examines the algorithmic limitations that arise due to biases, providing valuable insights into the challenges encountered by anomaly detection algorithms in accurately learning and capturing the entire range of variability present in the normative distribution. Through this analysis, we aim to enhance the understanding of these biases and pave the way for future improvements in the field. Here, we specifically investigate Alzheimer's disease detection from brain MR imaging as a case study, revealing significant biases related to sex, race, and scanner variations that substantially impact the results. These findings align with the broader goal of improving the reliability, fairness, and effectiveness of anomaly detection in medical imaging.

Esther Puyol-Antón, Bram Ruijsink, Baldeep S. Sidhu et al.

Left ventricular (LV) function is an important factor in terms of patient management, outcome, and long-term survival of patients with heart disease. The most recently published clinical guidelines for heart failure recognise that over reliance on only one measure of cardiac function (LV ejection fraction) as a diagnostic and treatment stratification biomarker is suboptimal. Recent advances in AI-based echocardiography analysis have shown excellent results on automated estimation of LV volumes and LV ejection fraction. However, from time-varying 2-D echocardiography acquisition, a richer description of cardiac function can be obtained by estimating functional biomarkers from the complete cardiac cycle. In this work we propose for the first time an AI approach for deriving advanced biomarkers of systolic and diastolic LV function from 2-D echocardiography based on segmentations of the full cardiac cycle. These biomarkers will allow clinicians to obtain a much richer picture of the heart in health and disease. The AI model is based on the 'nn-Unet' framework and was trained and tested using four different databases. Results show excellent agreement between manual and automated analysis and showcase the potential of the advanced systolic and diastolic biomarkers for patient stratification. Finally, for a subset of 50 cases, we perform a correlation analysis between clinical biomarkers derived from echocardiography and CMR and we show excellent agreement between the two modalities.

Emily Chan, Ciaran O'Hanlon, Carlota Asegurado Marquez et al.

Flow analysis carried out using phase contrast cardiac magnetic resonance imaging (PC-CMR) enables the quantification of important parameters that are used in the assessment of cardiovascular function. An essential part of this analysis is the identification of the correct CMR views and quality control (QC) to detect artefacts that could affect the flow quantification. We propose a novel deep learning based framework for the fully-automated analysis of flow from full CMR scans that first carries out these view selection and QC steps using two sequential convolutional neural networks, followed by automatic aorta and pulmonary artery segmentation to enable the quantification of key flow parameters. Accuracy values of 0.958 and 0.914 were obtained for view classification and QC, respectively. For segmentation, Dice scores were $>$0.969 and the Bland-Altman plots indicated excellent agreement between manual and automatic peak flow values. In addition, we tested our pipeline on an external validation data set, with results indicating good robustness of the pipeline. This work was carried out using multivendor clinical data consisting of 986 cases, indicating the potential for the use of this pipeline in a clinical setting.

Tiarna Lee, Esther Puyol-Antón, Bram Ruijsink et al.

In medical imaging, artificial intelligence (AI) is increasingly being used to automate routine tasks. However, these algorithms can exhibit and exacerbate biases which lead to disparate performances between protected groups. We investigate the impact of model choice on how imbalances in subject sex and race in training datasets affect AI-based cine cardiac magnetic resonance image segmentation. We evaluate three convolutional neural network-based models and one vision transformer model. We find significant sex bias in three of the four models and racial bias in all of the models. However, the severity and nature of the bias varies between the models, highlighting the importance of model choice when attempting to train fair AI-based segmentation models for medical imaging tasks.

Inês P. Machado, Esther Puyol-Antón, Kerstin Hammernik et al.

Cine cardiac magnetic resonance (CMR) imaging is considered the gold standard for cardiac function evaluation. However, cine CMR acquisition is inherently slow and in recent decades considerable effort has been put into accelerating scan times without compromising image quality or the accuracy of derived results. In this paper, we present a fully-automated, quality-controlled integrated framework for reconstruction, segmentation and downstream analysis of undersampled cine CMR data. The framework enables active acquisition of radial k-space data, in which acquisition can be stopped as soon as acquired data are sufficient to produce high quality reconstructions and segmentations. This results in reduced scan times and automated analysis, enabling robust and accurate estimation of functional biomarkers. To demonstrate the feasibility of the proposed approach, we perform realistic simulations of radial k-space acquisitions on a dataset of subjects from the UK Biobank and present results on in-vivo cine CMR k-space data collected from healthy subjects. The results demonstrate that our method can produce quality-controlled images in a mean scan time reduced from 12 to 4 seconds per slice, and that image quality is sufficient to allow clinically relevant parameters to be automatically estimated to within 5% mean absolute difference.

Jorge Mariscal-Harana, Clint Asher, Vittoria Vergani et al.

Artificial intelligence (AI) techniques have been proposed for automating analysis of short axis (SAX) cine cardiac magnetic resonance (CMR), but no CMR analysis tool exists to automatically analyse large (unstructured) clinical CMR datasets. We develop and validate a robust AI tool for start-to-end automatic quantification of cardiac function from SAX cine CMR in large clinical databases. Our pipeline for processing and analysing CMR databases includes automated steps to identify the correct data, robust image pre-processing, an AI algorithm for biventricular segmentation of SAX CMR and estimation of functional biomarkers, and automated post-analysis quality control to detect and correct errors. The segmentation algorithm was trained on 2793 CMR scans from two NHS hospitals and validated on additional cases from this dataset (n=414) and five external datasets (n=6888), including scans of patients with a range of diseases acquired at 12 different centres using CMR scanners from all major vendors. Median absolute errors in cardiac biomarkers were within the range of inter-observer variability: <8.4mL (left ventricle volume), <9.2mL (right ventricle volume), <13.3g (left ventricular mass), and <5.9% (ejection fraction) across all datasets. Stratification of cases according to phenotypes of cardiac disease and scanner vendors showed good performance across all groups. We show that our proposed tool, which combines image pre-processing steps, a domain-generalisable AI algorithm trained on a large-scale multi-domain CMR dataset and quality control steps, allows robust analysis of (clinical or research) databases from multiple centres, vendors, and cardiac diseases. This enables translation of our tool for use in fully-automated processing of large multi-centre databases.

Akshit Achara, Peter Triantafillou, Esther Puyol-Antón et al.

Deep neural networks often exploit shortcuts. These are spurious cues which are associated with output labels in the training data but are unrelated to task semantics. When the shortcut features are associated with sensitive attributes, shortcut learning can lead to biased model performance. Existing methods for localising and understanding shortcut learning are mostly based upon qualitative, image-level inspection and assume cues are human-visible, limiting their use in domains such as medical imaging. We introduce OSCAR (Ordinal Scoring Correlations for Attribution Representations), a model-agnostic framework for quantifying shortcut learning and localising shortcut features. OSCAR converts image-level task attribution maps into dataset-level rank profiles of image regions and compares them across three models: a balanced baseline model (BA), a test model (TS), and a sensitive attribute predictor (SA). By computing pairwise, partial, and deviation-based correlations on these rank profiles, we produce a set of quantitative metrics that characterise the degree of shortcut reliance for TS, together with a ranking of image-level regions that contribute most to it. Experiments on CelebA, CheXpert, and ADNI show that our correlations are (i) stable across seeds and partitions, (ii) sensitive to the level of association between shortcut features and output labels in the training data, and (iii) able to distinguish localised from diffuse shortcut features. As an illustration of the utility of our method, we show how worst-group performance disparities can be reduced using a simple test-time attenuation approach based on the identified shortcut regions. OSCAR provides a lightweight, pixel-space audit that yields statistical decision rules and spatial maps, enabling users to test, localise, and mitigate shortcut reliance. The code is available at https://github.com/acharaakshit/oscar

Tian Xia, Matthew Sinclair, Andreas Schuh et al.

Counterfactual image generation is a powerful tool for augmenting training data, de-biasing datasets, and modeling disease. Current approaches rely on external classifiers or regressors to increase the effectiveness of subject-level interventions (e.g., changing the patient's age). For structure-specific interventions (e.g., changing the area of the left lung in a chest radiograph), we show that this is insufficient, and can result in undesirable global effects across the image domain. Previous work used pixel-level label maps as guidance, requiring a user to provide hypothetical segmentations which are tedious and difficult to obtain. We propose Segmentor-guided Counterfactual Fine-Tuning (Seg-CFT), which preserves the simplicity of intervening on scalar-valued, structure-specific variables while producing locally coherent and effective counterfactuals. We demonstrate the capability of generating realistic chest radiographs, and we show promising results for modeling coronary artery disease. Code: https://github.com/biomedia-mira/seg-cft.

Dewmini Hasara Wickremasinghe, Yiyang Xu, Esther Puyol-Antón et al.

Quantification of cardiac biomarkers from cine cardiovascular magnetic resonance (CMR) data using deep learning (DL) methods offers many advantages, such as increased accuracy and faster analysis. However, only a few studies have focused on the scan-rescan precision of the biomarker estimates, which is important for reproducibility and longitudinal analysis. Here, we propose a cardiac biomarker estimation pipeline that not only focuses on achieving high segmentation accuracy but also on improving the scan-rescan precision of the computed biomarkers, namely left and right ventricular ejection fraction, and left ventricular myocardial mass. We evaluate two approaches to improve the apical-basal resolution of the segmentations used for estimating the biomarkers: one based on image interpolation and one based on segmentation interpolation. Using a database comprising scan-rescan cine CMR data acquired from 92 subjects, we compare the performance of these two methods against ground truth (GT) segmentations and DL segmentations obtained before interpolation (baseline). The results demonstrate that both the image-based and segmentation-based interpolation methods were able to narrow Bland-Altman scan-rescan confidence intervals for all biomarkers compared to the GT and baseline performances. Our findings highlight the importance of focusing not only on segmentation accuracy but also on the consistency of biomarkers across repeated scans, which is crucial for longitudinal analysis of cardiac function.

Tareen Dawood, Bram Ruijsink, Reza Razavi et al.

Improving calibration performance in deep learning (DL) classification models is important when planning the use of DL in a decision-support setting. In such a scenario, a confident wrong prediction could lead to a lack of trust and/or harm in a high-risk application. We evaluate the impact on accuracy and calibration of two types of approach that aim to improve DL classification model calibration: deterministic uncertainty methods (DUM) and uncertainty-aware training. Specifically, we test the performance of three DUMs and two uncertainty-aware training approaches as well as their combinations. To evaluate their utility, we use two realistic clinical applications from the field of cardiac imaging: artefact detection from phase contrast cardiac magnetic resonance (CMR) and disease diagnosis from the public ACDC CMR dataset. Our results indicate that both DUMs and uncertainty-aware training can improve both accuracy and calibration in both of our applications, with DUMs generally offering the best improvements. We also investigate the combination of the two approaches, resulting in a novel deterministic uncertainty-aware training approach. This provides further improvements for some combinations of DUMs and uncertainty-aware training approaches.

Zhen Yuan, David Stojanovski, Lei Li et al.

Splenomegaly, the enlargement of the spleen, is an important clinical indicator for various associated medical conditions, such as sickle cell disease (SCD). Spleen length measured from 2D ultrasound is the most widely used metric for characterising spleen size. However, it is still considered a surrogate measure, and spleen volume remains the gold standard for assessing spleen size. Accurate spleen volume measurement typically requires 3D imaging modalities, such as computed tomography or magnetic resonance imaging, but these are not widely available, especially in the Global South which has a high prevalence of SCD. In this work, we introduce a deep learning pipeline, DeepSPV, for precise spleen volume estimation from single or dual 2D ultrasound images. The pipeline involves a segmentation network and a variational autoencoder for learning low-dimensional representations from the estimated segmentations. We investigate three approaches for spleen volume estimation and our best model achieves 86.62%/92.5% mean relative volume accuracy (MRVA) under single-view/dual-view settings, surpassing the performance of human experts. In addition, the pipeline can provide confidence intervals for the volume estimates as well as offering benefits in terms of interpretability, which further support clinicians in decision-making when identifying splenomegaly. We evaluate the full pipeline using a highly realistic synthetic dataset generated by a diffusion model, achieving an overall MRVA of 83.0% from a single 2D ultrasound image. Our proposed DeepSPV is the first work to use deep learning to estimate 3D spleen volume from 2D ultrasound images and can be seamlessly integrated into the current clinical workflow for spleen assessment.

Iman Islam, Esther Puyol-Antón, Bram Ruijsink et al.

Echocardiography (echo) is the first imaging modality used when assessing cardiac function. The measurement of functional biomarkers from echo relies upon the segmentation of cardiac structures and deep learning models have been proposed to automate the segmentation process. However, in order to translate these tools to widespread clinical use it is important that the segmentation models are robust to a wide variety of images (e.g. acquired from different scanners, by operators with different levels of expertise etc.). To achieve this level of robustness it is necessary that the models are trained with multiple diverse datasets. A significant challenge faced when training with multiple diverse datasets is the variation in label presence, i.e. the combined data are often partially-labelled. Adaptations of the cross entropy loss function have been proposed to deal with partially labelled data. In this paper we show that training naively with such a loss function and multiple diverse datasets can lead to a form of shortcut learning, where the model associates label presence with domain characteristics, leading to a drop in performance. To address this problem, we propose a novel label dropout scheme to break the link between domain characteristics and the presence or absence of labels. We demonstrate that label dropout improves echo segmentation Dice score by 62% and 25% on two cardiac structures when training using multiple diverse partially labelled datasets.

Partha Shah, Durva Sankhe, Maariyah Rashid et al.

Artificial intelligence (AI) models to automatically classify skin lesions from dermatology images have shown promising performance but also susceptibility to bias by skin tone. The most common way of representing skin tone information is the Fitzpatrick Skin Tone (FST) scale. The FST scale has been criticised for having greater granularity in its skin tone categories for lighter-skinned subjects. This paper conducts an investigation of the impact (on performance and bias) on AI classification models of granularity in the FST scale. By training multiple AI models to classify benign vs. malignant lesions using FST-specific data of differing granularity, we show that: (i) when training models using FST-specific data based on three groups (FST 1/2, 3/4 and 5/6), performance is generally better for models trained on FST-specific data compared to a general model trained on FST-balanced data; (ii) reducing the granularity of FST scale information (from 1/2 and 3/4 to 1/2/3/4) can have a detrimental effect on performance. Our results highlight the importance of the granularity of FST groups when training lesion classification models. Given the question marks over possible human biases in the choice of categories in the FST scale, this paper provides evidence for a move away from the FST scale in fair AI research and a transition to an alternative scale that better represents the diversity of human skin tones.

Tiarna Lee, Esther Puyol-Antón, Bram Ruijsink et al.

Artificial intelligence (AI) is increasingly being used for medical imaging tasks. However, there can be biases in AI models, particularly when they are trained using imbalanced training datasets. One such example has been the strong ethnicity bias effect in cardiac magnetic resonance (CMR) image segmentation models. Although this phenomenon has been reported in a number of publications, little is known about the effectiveness of bias mitigation algorithms in this domain. We aim to investigate the impact of common bias mitigation methods to address bias between Black and White subjects in AI-based CMR segmentation models. Specifically, we use oversampling, importance reweighing and Group DRO as well as combinations of these techniques to mitigate the ethnicity bias. Second, motivated by recent findings on the root causes of AI-based CMR segmentation bias, we evaluate the same methods using models trained and evaluated on cropped CMR images. We find that bias can be mitigated using oversampling, significantly improving performance for the underrepresented Black subjects whilst not significantly reducing the majority White subjects' performance. Using cropped images increases performance for both ethnicities and reduces the bias, whilst adding oversampling as a bias mitigation technique with cropped images reduces the bias further. When testing the models on an external clinical validation set, we find high segmentation performance and no statistically significant bias.

Tareen Dawood, Chen Chen, Robin Andlauer et al.

Evaluation of predictive deep learning (DL) models beyond conventional performance metrics has become increasingly important for applications in sensitive environments like healthcare. Such models might have the capability to encode and analyse large sets of data but they often lack comprehensive interpretability methods, preventing clinical trust in predictive outcomes. Quantifying uncertainty of a prediction is one way to provide such interpretability and promote trust. However, relatively little attention has been paid to how to include such requirements into the training of the model. In this paper we: (i) quantify the data (aleatoric) and model (epistemic) uncertainty of a DL model for Cardiac Resynchronisation Therapy response prediction from cardiac magnetic resonance images, and (ii) propose and perform a preliminary investigation of an uncertainty-aware loss function that can be used to retrain an existing DL image-based classification model to encourage confidence in correct predictions and reduce confidence in incorrect predictions. Our initial results are promising, showing a significant increase in the (epistemic) confidence of true positive predictions, with some evidence of a reduction in false negative confidence.

Jorge Mariscal-Harana, Naomi Kifle, Reza Razavi et al.

Current artificial intelligence (AI) algorithms for short-axis cardiac magnetic resonance (CMR) segmentation achieve human performance for slices situated in the middle of the heart. However, an often-overlooked fact is that segmentation of the basal and apical slices is more difficult. During manual analysis, differences in the basal segmentations have been reported as one of the major sources of disagreement in human interobserver variability. In this work, we aim to investigate the performance of AI algorithms in segmenting basal and apical slices and design strategies to improve their segmentation. We trained all our models on a large dataset of clinical CMR studies obtained from two NHS hospitals (n=4,228) and evaluated them against two external datasets: ACDC (n=100) and M&Ms (n=321). Using manual segmentations as a reference, CMR slices were assigned to one of four regions: non-cardiac, base, middle, and apex. Using the nnU-Net framework as a baseline, we investigated two different approaches to reduce the segmentation performance gap between cardiac regions: (1) non-uniform batch sampling, which allows us to choose how often images from different regions are seen during training; and (2) a cardiac-region classification model followed by three (i.e. base, middle, and apex) region-specific segmentation models. We show that the classification and segmentation approach was best at reducing the performance gap across all datasets. We also show that improvements in the classification performance can subsequently lead to a significantly better performance in the segmentation task.

Katarína Tóthová, Sarah Parisot, Matthew Lee et al.

Surface reconstruction from magnetic resonance (MR) imaging data is indispensable in medical image analysis and clinical research. A reliable and effective reconstruction tool should: be fast in prediction of accurate well localised and high resolution models, evaluate prediction uncertainty, work with as little input data as possible. Current deep learning state of the art (SOTA) 3D reconstruction methods, however, often only produce shapes of limited variability positioned in a canonical position or lack uncertainty evaluation. In this paper, we present a novel probabilistic deep learning approach for concurrent 3D surface reconstruction from sparse 2D MR image data and aleatoric uncertainty prediction. Our method is capable of reconstructing large surface meshes from three quasi-orthogonal MR imaging slices from limited training sets whilst modelling the location of each mesh vertex through a Gaussian distribution. Prior shape information is encoded using a built-in linear principal component analysis (PCA) model. Extensive experiments on cardiac MR data show that our probabilistic approach successfully assesses prediction uncertainty while at the same time qualitatively and quantitatively outperforms SOTA methods in shape prediction. Compared to SOTA, we are capable of properly localising and orientating the prediction via the use of a spatially aware neural network.

Esther Puyol-Antón, Chen Chen, James R. Clough et al.

Advances in deep learning (DL) have resulted in impressive accuracy in some medical image classification tasks, but often deep models lack interpretability. The ability of these models to explain their decisions is important for fostering clinical trust and facilitating clinical translation. Furthermore, for many problems in medicine there is a wealth of existing clinical knowledge to draw upon, which may be useful in generating explanations, but it is not obvious how this knowledge can be encoded into DL models - most models are learnt either from scratch or using transfer learning from a different domain. In this paper we address both of these issues. We propose a novel DL framework for image-based classification based on a variational autoencoder (VAE). The framework allows prediction of the output of interest from the latent space of the autoencoder, as well as visualisation (in the image domain) of the effects of crossing the decision boundary, thus enhancing the interpretability of the classifier. Our key contribution is that the VAE disentangles the latent space based on `explanations' drawn from existing clinical knowledge. The framework can predict outputs as well as explanations for these outputs, and also raises the possibility of discovering new biomarkers that are separate (or disentangled) from the existing knowledge. We demonstrate our framework on the problem of predicting response of patients with cardiomyopathy to cardiac resynchronization therapy (CRT) from cine cardiac magnetic resonance images. The sensitivity and specificity of the proposed model on the task of CRT response prediction are 88.43% and 84.39% respectively, and we showcase the potential of our model in enhancing understanding of the factors contributing to CRT response.

Esther Puyol-Antón, Bram Ruijsink, James R. Clough et al.

Maintaining good cardiac function for as long as possible is a major concern for healthcare systems worldwide and there is much interest in learning more about the impact of different risk factors on cardiac health. The aim of this study is to analyze the impact of systolic blood pressure (SBP) on cardiac function while preserving the interpretability of the model using known clinical biomarkers in a large cohort of the UK Biobank population. We propose a novel framework that combines deep learning based estimation of interpretable clinical biomarkers from cardiac cine MR data with a variational autoencoder (VAE). The VAE architecture integrates a regression loss in the latent space, which enables the progression of cardiac health with SBP to be learnt. Results on 3,600 subjects from the UK Biobank show that the proposed model allows us to gain important insight into the deterioration of cardiac function with increasing SBP, identify key interpretable factors involved in this process, and lastly exploit the model to understand patterns of positive and adverse adaptation of cardiac function.

Katarína Tóthová, Sarah Parisot, Matthew C. H. Lee et al.

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.