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Generalization capabilities of learning-based medical image segmentation across domains are currently limited by the performance degradation caused by the domain shift, particularly for ultrasound (US) imaging. The quality of US images heavily relies on carefully tuned acoustic parameters, which vary across sonographers, machines, and settings. To improve the generalizability on US images across domains, we propose MI-SegNet, a novel mutual information (MI) based framework to explicitly disentangle the anatomical and domain feature representations; therefore, robust domain-independent segmentation can be expected. Two encoders are employed to extract the relevant features for the disentanglement. The segmentation only uses the anatomical feature map for its prediction. In order to force the encoders to learn meaningful feature representations a cross-reconstruction method is used during training …