Non-rigid multi-frame registration of cell nuclei in live cell microscopy image data

To gain a better understanding of cellular and molecular processes it is important to quantitatively analyze the motion of subcellular particles in live cell microscopy image sequences. For accurate quantification of the subcellular particle motion, compensation of the motion and deformation of the cell nucleus is required. This thesis deals with non-rigid registration of cell nuclei in 2D and 3D live cell fluorescence microscopy images. We developed two multi-frame non-rigid registration approaches which simultaneously exploit information from multiple consecutive frames of an image sequence to improve the registration accuracy. The multi-frame registration approaches are based on local optic flow estimation, use information from multiple consecutive images, and take into account computed transformations from previous time steps. The first approach comprises three intensity-based variants and two different temporal weighting schemes. The second approach determines diffeomorphic transformations in the log-domain which allows efficient computation of the inverse transformations. We use a temporally weighted mean image which is constructed based on inverse transformations and multiple consecutive frames. In addition, we employ a flow boundary preserving method for regularization of computed deformation vector fields. Both multi-frame registration approaches have been successfully applied to 2D and 3D synthetic as well as real live cell microscopy image sequences. We have performed an extensive quantitative evaluation of our approaches and compared their performance with previous non-rigid pairwise, multi-frame, and temporal groupwise registration approaches