A joint alignment and reconstruction algorithm for electron tomography to visualize in-depth cell-to-cell interactions

Electron tomography allows one to obtain 3D reconstructions visualizing a tissue’s ultrastructure from a series of 2D projection images. An inherent problem with this imaging technique is that its projection images contain unwanted shifts, which must be corrected for to achieve reliable reconstructions. Commonly, the projection images are aligned with each other by means of fiducial markers prior to the reconstruction procedure. In this work, we propose a joint alignment and reconstruction algorithm that iteratively solves for both the unknown reconstruction and the unintentional shift and does not require any fiducial markers. We evaluate the approach first on synthetic phantom data where the focus is not only on the reconstruction quality but more importantly on the shift correction. Subsequently, we apply the algorithm to healthy C57BL/6J mice and then compare it with non-obese diabetic (NOD) mice, with the aim of visualizing the attack of immune cells on pancreatic beta cells within type 1 diabetic mice at a more profound level through 3D analysis. We empirically demonstrate that the proposed algorithm is able to compute the shift with a remaining error at only the sub-pixel level and yields high-quality reconstructions for the limited-angle inverse problem. By decreasing labour and material costs, the algorithm facilitates further research directed towards investigating the immune system’s attacks in pancreata of NOD mice for numerous samples at different stages of type 1 diabetes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00418-022-02095-z.