Ghostbuster: A phase retrieval diffraction tomography algorithm for cryo-EM

Ewald sphere curvature correction, which extends beyond the projection approximation, stretches the shallow depth of field in cryo-EM reconstructions of thick particles. Here we show that even for previously assumed thin particles, reconstruction artifacts which we refer to as ghosts can appear. By retrieving the lost phases of the electron exitwaves and accounting for the first Born approximation scattering within the particle, we show that these ghosts can be effectively eliminated. Our simulations demonstrate how such ghostbusting can improve reconstructions as compared to existing state-of-the-art software. Like ptychographic cryo-EM, our Ghostbuster algorithm uses phase retrieval to improve reconstructions, but unlike the former, we do not need to modify the existing data acquisition pipelines. •Ewald sphere curvature correction methods for cryo-EM have had limited success due to lost phase information in measured micrographs.•Phase retrieval algorithms can recover these phases.•Backpropagating these phase-retrieved exitwaves through the sample can computationally stretch a cryo-EM reconstruction’s depth of field.