Recent advances in murine cardiac studies with three-dimensional cone beam micro-computed tomography (CT) have used either prospective or retrospective gating technique. While prospective gating ensures the best image quality and the highest resolution, it involves longer sampling times and higher radiation dose. Sampling is faster and the radiation dose can be reduced with retrospective gating but the image quality is affected by the limited number of projections with an irregular angular distribution which complicate the reconstruction process, causing significant streaking artifacts. This work involves both prospective and retrospective gating in sampling. Deformable registration is used between a high quality image set acquired with prospective gating with the multiple data sets during the cardiac cycle obtained using retrospective gating. Tests were conducted on a four-dimensional (4D) cardiac mouse phantom and after optimization, the method was applied to in vivo cardiac micro-CT data. Results indicate that, by using our method, the sampling time can be reduced by a factor of 2.5 and the radiation dose can be reduced 35% compared to the prospective sampling while the image quality can be maintained. In conclusion, we proposed a novel solution to 4D cine cardiac micro-CT based on a combined prospective with retrospective gating in sampling and deformable registration post reconstruction that mixed the advantages of both strategies.