Fast, spatially varying CTF correction in TEM.

We have developed new methods for contrast transfer function (CTF) correction of tilted and/or thick specimens. In order to achieve higher resolutions in cryo-electron tomography (CryoET), it is necessary to account for the defocus gradient on a tilted specimen and possibly the defocus gradient within a thick specimen. CTF correction methods which account for these defocus differences have recently gained interest. However, there is no global CTF correction method available to this date (to process the entire field-of-view at once) which can use different inverse filters, e.g. phase-flipping or Wiener filter, and which can do so within a reasonable time for realistic image sizes. We show that the CTF correction methods presented in this paper correctly account for the spatially varying defocus, can employ different inverse filters and are significantly faster (>50×) than existing methods. We provide proof-of-principle implementations of all the presented CTF correction methods online.