In the cell cycle, mitosis is the most dramatic phase, especially in Telophase and Cytokinesis. For single cells and cell
monolayer, there are precise microscopic studies of mitosis, while for 3-D tissue such as tumor spheroids the light signal
is obscured by the high background of diffusely scattered light. Therefore, the mitosis phase cannot be detected deep
inside 3-D tissue using conventional microscopic techniques. In this work, we detect mitosis in living tissue using Tissue
Dynamic Imaging (TDI). We trace depth-gated dynamic speckles from a tumor spheroid (up to 1mm in diameter) using
coherence-gated digital holography imaging. Frequency-versus-time spectrograms depend on specific types of
perturbation such as cell shape change, membrane undulation and cell organelles movements. By using these spectral
responses as functional finger prints, we can identify mitosis events from different voxels at a specified depth inside
tumor spheroids. By performing B-scans of the tumor spheroid, we generate 3-D mitosis maps (or movies) for the entire
tumor spheroids. We show that for healthy tumor spheroids, the mitosis events only happen within the proliferating shell.
We also compare results when anti-cancer drugs are applied to arrest, release and synchronize mitosis. This shows the
application of TDI for drug screening. The technique can identify and monitor complex motilities inside 3-D tissue with
a strong potential for drug diagnosis and developmental biology studies.