BackgroundSynchrotron radiation computed tomography (SR-CT) holds promise for high-resolution in vivo imaging. Notably, the reconstruction of SR-CT images necessitates a large set of data to be captured with sufficient photons from multiple angles, resulting in high radiation dose received by the object. Reducing the number of projections and/or photon flux is a straightforward means to lessen the radiation dose, however, compromises data completeness, thus introducing noises and artifacts. Deep learning (DL)-based supervised methods effectively denoise and remove artifacts, but they heavily depend on high-quality paired data acquired at high doses. Although algorithms exist for training without high-quality references, they struggle to effectively eliminate persistent artifacts present in real-world data. MethodsThis work presents a novel low-dose imaging strategy namely Sparse2Noise, which combines the reconstruction data from paired sparse-view CT scan (normal-flux) and full-view CT scan (low-flux) using a convolutional neural network (CNN). Sparse2Noise does not require high-quality reconstructed data as references and allows for fresh training on data with very small size. Sparse2Noise was evaluated by both simulated and experimental data. ResultsSparse2Noise effectively reduces noise and ring artifacts while maintaining high image quality, outperforming state-of-the-art image denoising methods at same dose levels. Furthermore, Sparse2Noise produces impressive high image quality for ex vivo rat hindlimb imaging with the acceptable low radiation dose (i.e., 0.5 Gy with the isotropic voxel size of 26 μm). ConclusionsThis work represents a significant advance towards in vivo SR-CT imaging. It is noteworthy that Sparse2Noise can also be used for denoising in conventional CT and/or phase-contrast CT.