RadDiff: Describing Differences in Radiology Image Sets with Natural Language

Understanding how two radiology image sets differ is critical for generating clinical insights and for interpreting medical AI systems. We introduce RadDiff, a multimodal agentic system that performs radiologist-style comparative reasoning to describe clinically meaningful differences between paired radiology studies. RadDiff builds on a proposer-ranker framework from VisDiff, and incorporates four innovations inspired by real diagnostic workflows: (1) medical knowledge injection through domain-adapted vision-language models; (2) multimodal reasoning that integrates images with their clinical reports; (3) iterative hypothesis refinement across multiple reasoning rounds; and (4) targeted visual search that localizes and zooms in on salient regions to capture subtle findings. To evaluate RadDiff, we construct RadDiffBench, a challenging benchmark comprising 57 expert-validated radiology study pairs with ground-truth difference descriptions. On RadDiffBench, RadDiff achieves 47% accuracy, and 50% accuracy when guided by ground-truth reports, significantly outperforming the general-domain VisDiff baseline. We further demonstrate RadDiff's versatility across diverse clinical tasks, including COVID-19 phenotype comparison, racial subgroup analysis, and discovery of survival-related imaging features. Together, RadDiff and RadDiffBench provide the first method-and-benchmark foundation for systematically uncovering meaningful differences in radiological data.