When the Edit Changes the Patient: Measuring Identity Preservation in Counterfactual Retinal Images

Counterfactual medical image generation have emerged as a critical tool for enhancing AI-driven systems in medical domain by answering "what-if" questions. However, existing approaches face two fundamental limitations: First, they fail to prevent unintended modifications, resulting collateral changes in demographic attributes when only disease features should be affected. Second, they lack interpretability in their editing process, which significantly limits their utility in real-world medical applications. To address these limitations, we present InstructX2X, a novel interpretable local editing model for counterfactual medical image generation featuring Region-Specific Editing. This approach restricts modifications to specific regions, effectively preventing unintended changes while simultaneously providing a Guidance Map that offers inherently interpretable visual explanations of the editing process. Additionally, we introduce MIMIC-EDIT-INSTRUCTION, a dataset for counterfactual medical image generation derived from expert-verified medical VQA pairs. Through extensive experiments, InstructX2X achieve state-of-the-art performance across all major evaluation metrics. Our model successfully generates high-quality counterfactual chest X-ray images along with interpretable explanations.

Medical image analysis is often hindered by biased datasets, which can lead to biased models and limited clinical applicability. A promising strategy for mitigating such biases is to augment training data with synthetic images. Counterfactual (CF) generation is one such strategy, though the term is used in two different senses: in some works, CFs are produced through causality-based interventions derived from structural causal models, whereas in others, they are produced by non-causal image edits or conventional conditional generative models, such as altering anatomy or adding pathologies. In this work, we study this distinction and evaluate its practical consequences for medical image augmentation. We compare three conditioning strategies: $\textit{Deterministic}$, which changes selected variables while holding the remaining variables fixed; $\textit{Undirected}$, which updates variables according to learned statistical associations without assigning causal directions; and $\textit{Causal}$, which propagates interventions along a directed causal graph. We analyse how these choices affect the resulting images, and explore when causally grounded methods improve dataset augmentation or bring limited benefit. In particular, we assess downstream performance and fairness, where fairness refers to reduced sensitivity to dataset biases across sensitive subgroups. Our experiments demonstrate that using a causal approach to synthetic training data generation can lead to tangible benefits, with these insights offering valuable guidance to machine learning practitioners for the effective design of data generation protocols.

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/.