On geometric artifacts in cryo electron tomography.

Single-tilt scheme is nowadays the prevalent acquisition geometry in electron tomography and subtomogram averaging experiments. Being an incomplete scheme that induces ill-posedness in the sense of the X-ray or Radon transform inverse problem, it introduces a number of artifacts that directly influence the quality of tomographic reconstructions. Though individually described by different authors before, a systematic study of these acquisition geometry-related artifacts in one place and across representative set of reconstruction methods has not been, to our knowledge, performed before. Moreover, the effects of these artifacts on the reconstructed density are sometimes misinterpreted, attributing them to the wrong cause, especially if their effects accumulate. In this work, we systematically study the major artifacts of single-tilt geometry known as the missing wedge (incomplete projection set problem), the missing information and the specimen-level interior problem (long-object problem). First, we illustratively describe, using a unified terminology, how and why these artifacts arise and when they can be avoided. Next, we describe the effects of these artifacts on the reconstructions across all major classes of reconstruction methods, including newly-appeared methods like the Iterative Nonuniform fast Fourier transform based Reconstruction method (INFR) and the Progressive Stochastic Reconstruction Technique (PSRT). Finally, we draw conclusions and recommendations on numerous points, especially regarding the mutual influence of the geometric artifacts, ability of different reconstruction methods to suppress them as well as implications to the interpretation of both electron tomography and subtomogram averaging experiments.