From Unsupervised to Zero-Shot: 3D Domain Adaptation for Cryo-Electron Tomography Segmentation.

With the refinement of 3D imaging modality, cryo-electron tomography (cryo-ET) has emerged as a powerful technique for the structural analysis of macromolecular complexes at near-atomic resolution. Recent advancements in volumetric segmentation methods applied to cryo-ET datasets have garnered significant attention within the biomedical sector. However, existing methods rely heavily on manually labeled data, which demands highly specialized expertise, making fully supervised approaches less feasible for cryo-ET images. To address this, a number of unsupervised domain adaptation (UDA) techniques have been developed to improve segmentation network performance using unlabeled data. Nevertheless, directly applying these methods to cryo-ET image segmentation presents two major challenges: 1) the source dataset, usually obtained through simulation, contains a fixed level of noise, while the target dataset, being directly collected from raw-data from the real-world scenario, has unpredictable noise levels; 2) the source data used for training typically consists of known macromolecules, in contrast, the target domain data are often unknown, causing the model to be biased towards those known macromolecules, leading to a domain shift problem. To address such challenges, in this paper, we introduce a voxel-wise unsupervised domain adaptation approach, termed Vox-UDA, specifically for cryo-ET subtomogram segmentation. Vox-UDA incorporates a noise generation module to simulate target-like noises in the source dataset for cross-noise level adaptation, and a denoised pseudo-labeling strategy based on the improved bilateral filter to alleviate the domain shift problem. Additionally, we further consider a scenario that is more in line with the real world, where the target (experimental) dataset might not be accessible during training or has a very small sample size, and we present a voxel-wise zero-shot domain adaptation (ZSDA) approach, named Vox-ZSDA. In Vox-ZSDA, we introduce a self-supervised graph learning strategy to eliminate any dependency on the target data, accompanied by a dynamic graph contrastive learning technique to enhance the model's sensitivity to macromolecular structures to boost the segmentation performance. More importantly, we construct the first UDA and ZSDA cryo-ET subtomogram segmentation benchmark on three experimental datasets. Extensive experimental results on multiple benchmarks and newly curated real-world datasets demonstrate the superiority of our proposed approach compared to state-of-the-art UDA and ZSDA methods.