Gradient projection for regularized cryo-electron tomographic reconstruction

Cryo-ET has recently emerged as a leading technique to investigate the three-dimensional (3D) structure of biological specimens at close-to-native state. The technique consists of acquiring many two-dimensional (2D) projections of the structure under scrutiny at various tilt angles under cryogenic conditions. The 3D structure is recovered through a number of steps including projection alignment and reconstruction. However, the resolution currently achieved by cryo-ET is well below the instrumental resolution mainly due to the contrast transfer function of the microscope, the limited tilt range and the high noise power. These limitations make the 3D reconstruction procedure very challenging. Here, we propose a new regularized reconstruction technique based on projected gradient algorithm. Using the gold-standard method for resolution assessment, the Fourier Shell Correlation, we show that the proposed technique outperforms the commonly used reconstruction methods in ET, including the filtered back projection and the algebraic reconstruction techniques.