Automatic alignment of transmission electron microscope tilt series without fiducial markers.

Accurate image alignment is needed for computing three-dimensional reconstructions from transmission electron microscope tilt series. So far, the best results have been obtained by using colloidal gold beads as fiducial markers. If their use has not been possible for some reason, the only option has been the automatic cross-correlation-based registration methods. However, the latter methods are inaccurate and, as we will show, inappropriate for the whole problem. Conversely, we propose a novel method that uses the actual 3D motion model but works without any fiducial markers in the images. The method is based on matching and tracking some interest points of the intensity surface by first solving the underlying geometrical constraint of consecutive images in the tilt series. The results show that our method is near the gold marker alignment in the level of accuracy and hence opens the way for new opportunities in the analysis of electron tomography reconstructions, especially when markers cannot be used.