A Fourier-based Approach for Iterative 3D Reconstruction from Cryo-EM Images

A major challenge in single particle reconstruction methods using cryo-electron microscopy is to attain a resolution sufficient to interpret fine details in three-dimensional (3D) macromolecular structures. Obtaining high resolution 3D reconstructions is difficult due to unknown orientations and positions of the imaged particles, possible incomplete coverage of the viewing directions, high level of noise in the projection images, and limiting effects of the contrast transfer function of the electron microscope. In this paper, we focus on the 3D reconstruction problem from projection images assuming an existing estimate for their orientations and positions. We propose a fast and accurate Fourier-based Iterative Reconstruction Method (FIRM) that exploits the Toeplitz structure of the operator A∗A, where A is the forward projector and A∗ is the back projector. The operator A∗A is equivalent to a convolution with a kernel. The kernel is pre-computed using the non-uniform Fast Fourier Transform and is efficiently applied in each iteration step. The iterations by FIRM are therefore considerably faster than those of traditional iterative algebraic approaches, while maintaining the same accuracy even when the viewing directions are unevenly distributed. The time complexity of FIRM is comparable to the direct Fourier inversion method. Moreover, FIRM combines images from different defocus groups simultaneously and can handle a wide range of regularization terms. We provide experimental results on simulated data that demonstrate the speed and accuracy of FIRM in comparison with current methods.