Current deep-learning-based registration algorithms often exploit intensity-based similarity measures as the loss function, where dense correspondence between a pair of moving and fixed images is optimized through backpropagation during training. However, intensity-based metrics can be misleading when the assumption of intensity class correspondence is violated, especially in cross-modality or contrast-enhanced images. Moreover, existing learning-based registration methods are predominantly

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... icable to pairwise registration and are rarely extended to groupwise registration or simultaneous registration with multiple images. In this paper, we propose a new image registration framework based on multivariate mixture model (MvMM) and neural network estimation. A generative model consolidating both appearance and anatomical information is established to derive a novel loss function capable of implementing groupwise registration. We highlight the versatility of the proposed framework for various applications on multimodal cardiac images, including single-atlas-based segmentation (SAS) via pairwise registration and multi-atlas segmentation (MAS) unified by groupwise registration. We evaluated performance on two publicly available datasets, i.e. MM-WHS-2017 and MS-CMRSeg-2019. The results show that the proposed framework achieved an average Dice score of 0.871± 0.025 for whole-heart segmentation on MR images and 0.783± 0.082 for myocardium segmentation on LGE MR images.