Abstract:Weakly supervised medical image segmentation (MIS) using generative models is crucial for clinical diagnosis. However, the accuracy of the segmentation results is often limited by insufficient supervision and the complex nature of medical imaging. Existing models also only provide a single outcome, which does not allow for the measurement of uncertainty. In this paper, we introduce DiffSeg, a segmentation model for skin lesions based on diffusion difference which exploits diffusion model principles to ex-tract noise-based features from images with diverse semantic information. By discerning difference between these noise features, the model identifies diseased areas. Moreover, its multi-output capability mimics doctors' annotation behavior, facilitating the visualization of segmentation result consistency and ambiguity. Additionally, it quantifies output uncertainty using Generalized Energy Distance (GED), aiding interpretability and decision-making for physicians. Finally, the model integrates outputs through the Dense Conditional Random Field (DenseCRF) algorithm to refine the segmentation boundaries by considering inter-pixel correlations, which improves the accuracy and optimizes the segmentation results. We demonstrate the effectiveness of DiffSeg on the ISIC 2018 Challenge dataset, outperforming state-of-the-art U-Net-based methods.