Interpretable multimodal retrieval augmented diagnosis for breast ultrasound with multinational clinical validation and reader study

Breast ultrasound is central to breast cancer diagnosis but suffers from substantial inter-observer variability in Breast Imaging Reporting and Data System (BI-RADS) assessment, and existing deep learning models remain opaque. Multimodal large language models promise interpretable report-based reasoning, yet scarce paired image-report data yields weak visual-semantic alignment. We propose B-RAD, a BI-RADS-aware retrieval-augmented diagnosis framework that mirrors the radiologist workflow of retrieving exemplars, localizing lesions, and determining the BI-RADS category. Its retrieval module learns BI-RADS-aware alignment from unpaired data by jointly minimizing cross-modal mismatch and ordinal prediction error. Retrieved exemplars guide few-shot detection of the lesion together with its margin and posterior acoustic features, and the detected region prompts a segmentation model whose mask drives training-free foveal attention for classification. We validated B-RAD on eleven cohorts from seven countries totaling 8311 images, spanning internal validation and three external cohorts including an independent institutional cohort. The full pipeline reached a biopsy triage AUROC of 0.952 on that institutional cohort without fine-tuning, outperforming existing vision-language models. In a four-reader study, B-RAD assistance improved accuracy, raised inter-reader agreement from moderate to substantial, and reduced missed malignancies across all readers. These findings show that retrieval-augmented diagnosis can narrow the expertise gap and support accessible breast cancer screening in resource-limited settings.