Medical expert annotators are scarce, and blind reliance on artificial intelligence (AI) can be misleading, motivating approaches in which humans, particularly junior medical trainees or even non-medical personnel, collaborate with AI to achieve robust medical segmentation. Although the Segment Anything Model (SAM) shows promise for general-purpose image segmentation, its performance in human-AI collaboration for specialized medical tasks has not been thoroughly evaluated. Here we present Hi-Seg, a human-in-the-loop segmentation framework for pulmonary nodules built on SAM. Humans iteratively refine prompts through trial-and-error learning and semantic reasoning, progressively guiding SAM toward higher-quality masks. Using chest CT scans from 1,179 patients across 12 centers, we conducted the first large-scale external validation of collaborative human-SAM segmentation. Across all annotator groups, Hi-Seg achieved a mean Dice score of almost 85%, outperforming five state-of-the-art deep learning models by 10-22% and 13 SAM variants by 1-29%. Hi-Seg improved segmentation accuracy while reducing annotation time for medical annotators, and briefly trained non-medical annotators achieved performance comparable to that of the junior medical student. These findings suggest that human-in-the-loop segmentation can reduce clinician workload, enable scalable crowdsourced annotation, and transform clinical workflows by facilitating the safe and efficient integration of foundation models into routine clinical practice.
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