Abstract:4D medical image interpolation is essential for improving temporal resolution and diagnostic precision in clinical applications. Previous works ignore the problem of distribution shifts, resulting in poor generalization under different distribution. A natural solution would be to adapt the model to a new test distribution, but this cannot be done if the test input comes without a ground truth label. In this paper, we propose a novel test time training framework which uses self-supervision to adapt the model to a new distribution without requiring any labels. Indeed, before performing frame interpolation on each test video, the model is trained on the same instance using a self-supervised task, such as rotation prediction or image reconstruction. We conduct experiments on two publicly available 4D medical image interpolation datasets, Cardiac and 4D-Lung. The experimental results show that the proposed method achieves significant performance across various evaluation metrics on both datasets. It achieves higher peak signal-to-noise ratio values, 33.73dB on Cardiac and 34.02dB on 4D-Lung. Our method not only advances 4D medical image interpolation but also provides a template for domain adaptation in other fields such as image segmentation and image registration.