Deep learning models can perform well in complex medical imaging classification tasks, even when basing their conclusions on spurious correlations (i.e. confounders), should they be prevalent in the training dataset, rather than on the causal image markers of interest. This would thereby limit their ability to generalize across the population. Explainability based on counterfactual image generation can be used to expose the confounders but does not provide a strategy to mitigate the bias. In this work, we introduce the first end-to-end training framework that integrates both (i) popular debiasing classifiers (e.g. distributionally robust optimization (DRO)) to avoid latching onto the spurious correlations and (ii) counterfactual image generation to unveil generalizable imaging markers of relevance to the task. Additionally, we propose a novel metric, Spurious Correlation Latching Score (SCLS), to quantify the extent of the classifier reliance on the spurious correlation as exposed by the counterfactual images. Through comprehensive experiments on two public datasets (with the simulated and real visual artifacts), we demonstrate that the debiasing method: (i) learns generalizable markers across the population, and (ii) successfully ignores spurious correlations and focuses on the underlying disease pathology.
The discovery of patient-specific imaging markers that are predictive of future disease outcomes can help us better understand individual-level heterogeneity of disease evolution. In fact, deep learning models that can provide data-driven personalized markers are much more likely to be adopted in medical practice. In this work, we demonstrate that data-driven biomarker discovery can be achieved through a counterfactual synthesis process. We show how a deep conditional generative model can be used to perturb local imaging features in baseline images that are pertinent to subject-specific future disease evolution and result in a counterfactual image that is expected to have a different future outcome. Candidate biomarkers, therefore, result from examining the set of features that are perturbed in this process. Through several experiments on a large-scale, multi-scanner, multi-center multiple sclerosis (MS) clinical trial magnetic resonance imaging (MRI) dataset of relapsing-remitting (RRMS) patients, we demonstrate that our model produces counterfactuals with changes in imaging features that reflect established clinical markers predictive of future MRI lesional activity at the population level. Additional qualitative results illustrate that our model has the potential to discover novel and subject-specific predictive markers of future activity.