Technologically advanced imaging techniques have allowed us to generate and study the internal part of a tissue over time by capturing serial optical images that contain spatio-temporal slices of hundreds of tightly packed cells. Image registration of such live-imaging datasets of developing multicelluar tissues is one of the essential components of all image analysis pipelines. In this paper, we present a fully automated 4D(X-Y-Z-T) registration method of live imaging stacks that takes care of both temporal and spatial misalignments. We present a novel landmark selection methodology where the shape features of individual cells are not of high quality and highly distinguishable. The proposed registration method finds the best image slice correspondence from consecutive image stacks to account for vertical growth in the tissue and the discrepancy in the choice of the starting focal point. Then, it uses local graph-based approach to automatically find corresponding landmark pairs, and finally the registration parameters are used to register the entire image stack. The proposed registration algorithm combined with an existing tracking method is tested on multiple image stacks of tightly packed cells of Arabidopsis shoot apical meristem and the results show that it significantly improves the accuracy of cell lineages and division statistics.
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