In mathematical imaging a vast variety of different models and methods exists to track cells with fluorescence markers. Fluorescence imaging has the advantage of excellent signal to noise ratio, which allows for simple tracking algorithms to be applied. The disadvantage of fluorescence imaging methods is the adverse effect of fluorescent illumination on especially mammalian cells during mitosis. Cells often are arrested in mitosis when light levels are too high. One specific problem, which has wide applications, is the development of tools for automatic mitosis detection and tracking. This is particularly important for different types of cancer cells when using phase contrast microscopy. Phase contrast is the most widely-used contrast method in light microscopy. Every tissue culture microscope is equipped with phase contrast. Time-lapse observations of cell divisions are a measurement to determine the percentage of cells undergoing mitosis (mitotic index analysis). The mitotic index is an important prognostic factor predicting both overall survival and response to chemotherapy in most types of cancer. Duration of the cell cycle and mitosis vary in different cell types. An elevated mitotic index indicates more cells are dividing, and thus is one of the key measurements in cancer drug development studies.