Medical image segmentation plays an important role in computer aided diagnosis, treatment planning, and disease monitoring. U-Net has been widely used for biomedical image segmentation because of its encoder decoder structure and skip connections. However, conventional convolution based U-Net models may have limited ability to capture long range dependencies and global contextual information, which can affect performance in complex segmentation tasks. This paper presents a comparative study of five U-Net based architectures: U-Net 3D, Residual U-Net, Attention U-Net, UNETR, and Swin UNETR. The models are evaluated on two benchmark datasets: BraTS 2023 for brain tumor segmentation and DRIVE for retinal vessel segmentation. Experimental results show that Swin UNETR achieves the best overall performance, with Dice scores of 0.8965 on BraTS 2023 and 0.8078 on DRIVE. The results suggest that transformer based U-Net variants are effective for segmentation tasks requiring global contextual modeling, while residual learning remains useful for fine structure segmentation. This study provides practical insights into model selection for medical image segmentation across volumetric MRI and retinal imaging tasks.

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