Restoration of high-tilt electron micrographs using a focus series

Electron microscopy tomography requires high-tilt projections. However, the variation in defocus over a highly tilted specimen results in a blurred micrograph, where the blur is spatially varying blur can cause the micrograph to deviate from an acceptable approximation of the projection of the specimen's density function. In practice, this has been one factor limiting reconstructions of large cellular areas. We derive an algorithm to restore, or deblur, high-tilt electron micrographs using multiple defocused versions of the micrograph. This algorithm consists of digitization and registration of the micrographs, identification of the defocus blur using either a theoretical model or a zero-tilt focus series, and spatially varying restoration using the multiple high-tilt defocused micrographs. Numerical results using simulated and real data are presented, demonstrating the effectiveness of this algorithm.