Multi-Agent Reasoning for Cardiovascular Imaging Phenotype Analysis

Abstract

Identifying associations between imaging phenotypes, disease risk factors, and clinical outcomes is essential for understanding disease mechanisms. However, traditional approaches rely on human-driven hypothesis testing and selection of association factors, often overlooking complex, non-linear dependencies among imaging phenotypes and other multi-modal data. To address this, we introduce Multi-agent Exploratory Synergy for the Heart (MESHAgents): a framework that leverages large language models as agents to dynamically elicit, surface, and decide confounders and phenotypes in association studies. Specifically, we orchestrate a multi-disciplinary team of AI agents, which spontaneously generate and converge on insights through iterative, self-organizing reasoning. The framework dynamically synthesizes statistical correlations with multi-expert consensus, providing an automated pipeline for phenome-wide association studies (PheWAS). We demonstrate the system's capabilities through a population-based study of imaging phenotypes of the heart and aorta. MESHAgents autonomously uncovered correlations between imaging phenotypes and a wide range of non-imaging factors, identifying additional confounder variables beyond standard demographic factors. Validation on diagnosis tasks reveals that MESHAgents-discovered phenotypes achieve performance comparable to expert-selected phenotypes, with mean AUC differences as small as $-0.004_{\pm0.010}$ on disease classification tasks. Notably, the recall score improves for 6 out of 9 disease types. Our framework provides clinically relevant imaging phenotypes with transparent reasoning, offering a scalable alternative to expert-driven methods.