A General Bézier Tree Encoding Counterfactual Framework for Retinal-Vessel-Mediated Disease Analysis

Visual Counterfactual Explanations (VCEs) aim to explain image classifiers by generating minimally edited and realistic versions of an input image that change the classifier's prediction. Existing VCE methods are inherently classifier-dependent and therefore susceptible to classifier biases and failure modes, such as sensitivity to shortcut features and calibration errors. In this paper, we propose a classifier-free approach for visual counterfactual generation based on Contrastive Analysis (CA). Given two datasets corresponding to different classes (e.g., healthy and patients), we disentangle the generative factors that are common across the two datasets from those that are salient to each dataset, and generate counterfactual images by swapping only the salient factors. By operating directly on data distributions rather than decision boundaries, our method provides model-agnostic VCEs that are less sensitive to classifier biases. Our approach leverages the high-quality synthesis and well-structured latent space of StyleGAN2. We use the feature space F, instead than the usual W-space, to improve detail preservation. Unlike conventional CA approaches, which typically assume salient factors in only one dataset, we introduce an adapted framework and loss functions for VCE that allow multiple salient factors in each dataset. We evaluate our method on three medical imaging datasets and demonstrate superior counterfactual generation quality compared to existing approaches.

Counterfactual image generation answers questions about how a subject would have looked under retrospective, hypothetical scenarios. Recent methods have improved perceptual quality, identity preservation and faithfulness to an underlying causal model, but their adoption in healthcare is limited by scarce annotated data, distribution shift between datasets, and mismatches between pretrained generative models and those required for counterfactual inference. We propose specialisation, a data and parameter-efficient framework for adapting pretrained, non-causal generative models into causal mechanisms under distribution shift. Based on this framework, we train a radiology counterfactual image generation model, called RadCF, using latent flow matching. We validate our approach on three chest X-ray datasets spanning different dataset shifts, data volumes, and counterfactual questions, associated with challenging, highly-localised interventions. Our results show that RadCF and specialisation improve counterfactual soundness over existing methods while being data and parameter efficient, and that the resulting counterfactuals can detect and mitigate shortcut learning in a downstream medical classifier. Code is available at https://github.com/GSK-AI/RadCF/.

Automatic extraction of retinal vascular biomarkers from color fundus images (CFI) is crucial for large-scale studies of the retinal vasculature. We present VascX, an open-source Python toolbox that extracts biomarkers from CFI artery-vein segmentations. VascX starts from vessel segmentation masks, extracts their skeletons, builds undirected and directed vessel graphs, and resolves vessel segments into longer vessels. A comprehensive set of biomarkers is derived, including vascular density, central retinal equivalents (CREs), and tortuosity. Spatially localized biomarkers may be calculated over grids placed relative to the fovea and optic disc. VascX is released via GitHub and PyPI with comprehensive documentation and examples. Our test-retest reproducibility analysis on repeat imaging of the same eye by different devices shows that most VascX biomarkers have moderate to excellent agreement (ICC > 0.5), with important differences in the level of robustness of different biomarkers. Our analyses of biomarker sensitivity to image perturbations and heuristic parameter values support these differences and further characterize VascX biomarkers. Ultimately, VascX provides an explainable and easily modifiable feature-extraction toolbox that complements segmentation to produce reliable retinal vascular biomarkers. Our graph-based biomarker computation stages support reproducible, region-aware measurements suited for large-scale clinical and epidemiological research. By enabling easy extraction of existing biomarkers and rapid experimentation with new ones, VascX supports oculomics research. Its robustness and computational efficiency facilitate scalable deployment in large databases, while open-source distribution lowers barriers to adoption for ophthalmic researchers and clinicians.