Predicting risk of cardiovascular disease using retinal OCT imaging

We investigated the potential of optical coherence tomography (OCT) as an additional imaging technique to predict future cardiovascular disease (CVD). We utilised a self-supervised deep learning approach based on Variational Autoencoders (VAE) to learn low-dimensional representations of high-dimensional 3D OCT images and to capture distinct characteristics of different retinal layers within the OCT image. A Random Forest (RF) classifier was subsequently trained using the learned latent features and participant demographic and clinical data, to differentiate between patients at risk of CVD events (MI or stroke) and non-CVD cases. Our predictive model, trained on multimodal data, was assessed based on its ability to correctly identify individuals likely to suffer from a CVD event(MI or stroke), within a 5-year interval after image acquisition. Our self-supervised VAE feature selection and multimodal Random Forest classifier differentiate between patients at risk of future CVD events and the control group with an AUC of 0.75, outperforming the clinically established QRISK3 score (AUC= 0.597). The choroidal layer visible in OCT images was identified as an important predictor of future CVD events using a novel approach to model explanability. Retinal OCT imaging provides a cost-effective and non-invasive alternative to predict the risk of cardiovascular disease and is readily accessible in optometry practices and hospitals.

Source Matters: Source Dataset Impact on Model Robustness in Medical Imaging

Transfer learning has become an essential part of medical imaging classification algorithms, often leveraging ImageNet weights. However, the domain shift from natural to medical images has prompted alternatives such as RadImageNet, often demonstrating comparable classification performance. However, it remains unclear whether the performance gains from transfer learning stem from improved generalization or shortcut learning. To address this, we investigate potential confounders -- whether synthetic or sampled from the data -- across two publicly available chest X-ray and CT datasets. We show that ImageNet and RadImageNet achieve comparable classification performance, yet ImageNet is much more prone to overfitting to confounders. We recommend that researchers using ImageNet-pretrained models reexamine their model robustness by conducting similar experiments. Our code and experiments are available at https://github.com/DovileDo/source-matters.

Multi-view Hybrid Graph Convolutional Network for Volume-to-mesh Reconstruction in Cardiovascular MRI

Cardiovascular magnetic resonance imaging is emerging as a crucial tool to examine cardiac morphology and function. Essential to this endeavour are anatomical 3D surface and volumetric meshes derived from CMR images, which facilitate computational anatomy studies, biomarker discovery, and in-silico simulations. However, conventional surface mesh generation methods, such as active shape models and multi-atlas segmentation, are highly time-consuming and require complex processing pipelines to generate simulation-ready 3D meshes. In response, we introduce HybridVNet, a novel architecture for direct image-to-mesh extraction seamlessly integrating standard convolutional neural networks with graph convolutions, which we prove can efficiently handle surface and volumetric meshes by encoding them as graph structures. To further enhance accuracy, we propose a multiview HybridVNet architecture which processes both long axis and short axis CMR, showing that it can increase the performance of cardiac MR mesh generation. Our model combines traditional convolutional networks with variational graph generative models, deep supervision and mesh-specific regularisation. Experiments on a comprehensive dataset from the UK Biobank confirm the potential of HybridVNet to significantly advance cardiac imaging and computational cardiology by efficiently generating high-fidelity and simulation ready meshes from CMR images.

Unsupervised bias discovery in medical image segmentation

It has recently been shown that deep learning models for anatomical segmentation in medical images can exhibit biases against certain sub-populations defined in terms of protected attributes like sex or ethnicity. In this context, auditing fairness of deep segmentation models becomes crucial. However, such audit process generally requires access to ground-truth segmentation masks for the target population, which may not always be available, especially when going from development to deployment. Here we propose a new method to anticipate model biases in biomedical image segmentation in the absence of ground-truth annotations. Our unsupervised bias discovery method leverages the reverse classification accuracy framework to estimate segmentation quality. Through numerical experiments in synthetic and realistic scenarios we show how our method is able to successfully anticipate fairness issues in the absence of ground-truth labels, constituting a novel and valuable tool in this field.

CheXmask: a large-scale dataset of anatomical segmentation masks for multi-center chest x-ray images

The development of successful artificial intelligence models for chest X-ray analysis relies on large, diverse datasets with high-quality annotations. While several databases of chest X-ray images have been released, most include disease diagnosis labels but lack detailed pixel-level anatomical segmentation labels. To address this gap, we introduce an extensive chest X-ray multi-center segmentation dataset with uniform and fine-grain anatomical annotations for images coming from six well-known publicly available databases: CANDID-PTX, ChestX-ray8, Chexpert, MIMIC-CXR-JPG, Padchest, and VinDr-CXR, resulting in 676,803 segmentation masks. Our methodology utilizes the HybridGNet model to ensure consistent and high-quality segmentations across all datasets. Rigorous validation, including expert physician evaluation and automatic quality control, was conducted to validate the resulting masks. Additionally, we provide individualized quality indices per mask and an overall quality estimation per dataset. This dataset serves as a valuable resource for the broader scientific community, streamlining the development and assessment of innovative methodologies in chest X-ray analysis. The CheXmask dataset is publicly available at: \url{https://physionet.org/content/chexmask-cxr-segmentation-data/}.

Towards unraveling calibration biases in medical image analysis

In recent years the development of artificial intelligence (AI) systems for automated medical image analysis has gained enormous momentum. At the same time, a large body of work has shown that AI systems can systematically and unfairly discriminate against certain populations in various application scenarios. These two facts have motivated the emergence of algorithmic fairness studies in this field. Most research on healthcare algorithmic fairness to date has focused on the assessment of biases in terms of classical discrimination metrics such as AUC and accuracy. Potential biases in terms of model calibration, however, have only recently begun to be evaluated. This is especially important when working with clinical decision support systems, as predictive uncertainty is key for health professionals to optimally evaluate and combine multiple sources of information. In this work we study discrimination and calibration biases in models trained for automatic detection of malignant dermatological conditions from skin lesions images. Importantly, we show how several typically employed calibration metrics are systematically biased with respect to sample sizes, and how this can lead to erroneous fairness analysis if not taken into consideration. This is of particular relevance to fairness studies, where data imbalance results in drastic sample size differences between demographic sub-groups, which, if not taken into account, can act as confounders.

Are demographically invariant models and representations in medical imaging fair?

Medical imaging models have been shown to encode information about patient demographics (age, race, sex) in their latent representation, raising concerns about their potential for discrimination. Here, we ask whether it is feasible and desirable to train models that do not encode demographic attributes. We consider different types of invariance with respect to demographic attributes - marginal, class-conditional, and counterfactual model invariance - and lay out their equivalence to standard notions of algorithmic fairness. Drawing on existing theory, we find that marginal and class-conditional invariance can be considered overly restrictive approaches for achieving certain fairness notions, resulting in significant predictive performance losses. Concerning counterfactual model invariance, we note that defining medical image counterfactuals with respect to demographic attributes is fraught with complexities. Finally, we posit that demographic encoding may even be considered advantageous if it enables learning a task-specific encoding of demographic features that does not rely on human-constructed categories such as 'race' and 'gender'. We conclude that medical imaging models may need to encode demographic attributes, lending further urgency to calls for comprehensive model fairness assessments in terms of predictive performance.

Unsupervised ensemble-based phenotyping helps enhance the discoverability of genes related to heart morphology

Recent genome-wide association studies (GWAS) have been successful in identifying associations between genetic variants and simple cardiac parameters derived from cardiac magnetic resonance (CMR) images. However, the emergence of big databases including genetic data linked to CMR, facilitates investigation of more nuanced patterns of shape variability. Here, we propose a new framework for gene discovery entitled Unsupervised Phenotype Ensembles (UPE). UPE builds a redundant yet highly expressive representation by pooling a set of phenotypes learned in an unsupervised manner, using deep learning models trained with different hyperparameters. These phenotypes are then analyzed via (GWAS), retaining only highly confident and stable associations across the ensemble. We apply our approach to the UK Biobank database to extract left-ventricular (LV) geometric features from image-derived three-dimensional meshes. We demonstrate that our approach greatly improves the discoverability of genes influencing LV shape, identifying 11 loci with study-wide significance and 8 with suggestive significance. We argue that our approach would enable more extensive discovery of gene associations with image-derived phenotypes for other organs or image modalities.

Multi-center anatomical segmentation with heterogeneous labels via landmark-based models

Learning anatomical segmentation from heterogeneous labels in multi-center datasets is a common situation encountered in clinical scenarios, where certain anatomical structures are only annotated in images coming from particular medical centers, but not in the full database. Here we first show how state-of-the-art pixel-level segmentation models fail in naively learning this task due to domain memorization issues and conflicting labels. We then propose to adopt HybridGNet, a landmark-based segmentation model which learns the available anatomical structures using graph-based representations. By analyzing the latent space learned by both models, we show that HybridGNet naturally learns more domain-invariant feature representations, and provide empirical evidence in the context of chest X-ray multiclass segmentation. We hope these insights will shed light on the training of deep learning models with heterogeneous labels from public and multi-center datasets.

Improving anatomical plausibility in medical image segmentation via hybrid graph neural networks: applications to chest x-ray analysis

Anatomical segmentation is a fundamental task in medical image computing, generally tackled with fully convolutional neural networks which produce dense segmentation masks. These models are often trained with loss functions such as cross-entropy or Dice, which assume pixels to be independent of each other, thus ignoring topological errors and anatomical inconsistencies. We address this limitation by moving from pixel-level to graph representations, which allow to naturally incorporate anatomical constraints by construction. To this end, we introduce HybridGNet, an encoder-decoder neural architecture that leverages standard convolutions for image feature encoding and graph convolutional neural networks (GCNNs) to decode plausible representations of anatomical structures. We also propose a novel image-to-graph skip connection layer which allows localized features to flow from standard convolutional blocks to GCNN blocks, and show that it improves segmentation accuracy. The proposed architecture is extensively evaluated in a variety of domain shift and image occlusion scenarios, and audited considering different types of demographic domain shift. Our comprehensive experimental setup compares HybridGNet with other landmark and pixel-based models for anatomical segmentation in chest x-ray images, and shows that it produces anatomically plausible results in challenging scenarios where other models tend to fail.