Abstract: Accurate histopathological image segmentation is crucial for precise disease diagnosis and prognosis. Yet, challenges like staining variations, imaging conditions, and tissue diversity impede model generalization across domains, such as different institutes or organs. Traditional domain generalization (DG) techniques, such as data augmentation and feature alignment, excel in classification tasks but face challenges in segmentation tasks due to their dense prediction requirements. These tasks are particularly computationally demanding, and are complicated due to the fine-grained feature variability that arises from the domain differences in histopathological images. To tackle this, we propose the Shallow-Deep Synergy (SDS) approach for the U-Net-based segmentation framework, which capitalizes on the distinctive characteristics of both shallow and deep layers of the U-Net. Specifically, we introduce the fine-grained domain variations in image intensities and textures for shallow layers, while focusing on aligning the pixel-level classification decision boundaries in deep layers by adjusting the optimization trajectory through class-wise gradient and feature alignment. Moreover, the SDS is equipped with a big-batch strategy further boosting alignment efficiency, achieving high accuracy without substantial GPU memory. Extensive experiments conducted on two histopathological segmentation datasets, each representing different domain types, demonstrate that the proposed SDS achieves superior generalization performance compared to existing domain generalization methods, even being competitive with intra-domain models in some cases.
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