Automated Tracking of Mouse Embryogenesis from Large-scale Fluorescence Microscopy Data

Recent breakthroughs in microscopy techniques and fluorescence probes enable the recording of mouse embryogenesis at the cellular level for days, easily generating terabyte-level 3D time-lapse data. Since millions of cells are involved, this information-rich data brings a natural demand for an automated tool for its comprehensive analysis. This tool should automatically (1) detect and segment cells at each time point and (2) track cell migration across time. Most existing cell tracking methods cannot scale to the data with such large size and high complexity. For those purposely designed for embryo data analysis, the accuracy is heavily sacrificed. Here, we present a new computational framework for the mouse embryo data analysis with high accuracy and efficiency. Our framework detects and segments cells with a fully probability-principled method, which not only has high statistical power but also helps determine the desired cell territories and increase the segmentation accuracy. With the cells detected at each time point, our framework reconstructs cell traces with a new minimum-cost circulation-based paradigm, CINDA (CIrculation Network-based DataAssociation). Compared with the widely used minimum-cost flow-based methods, CINDA guarantees the global optimal solution with the best-of-known theoretical worst-case complexity and hundreds to thousands of times practical efficiency improvement. Since the information extracted from a single time point is limited, our framework iteratively refines cell detection and segmentation results based on the cell traces which contain more information from other time points. Results show that this dramatically improves the accuracy of cell detection, segmentation, and tracking. To make our work easy to use, we designed a standalone software, MIVAQ (Microscopic Image Visualization, Annotation, and Quantification), with our framework as the backbone and a user-friendly interface. With MIVAQ, users can easily analyze their data and visually check the results.