Label-free mitosis detection in tumor spheroids using tissue dynamics imaging

Ran An; Kwan Jeong; John Turek; David Nolte

doi:10.1117/12.907658

13 February 2012 Label-free mitosis detection in tumor spheroids using tissue dynamics imaging

Ran An, Kwan Jeong, John Turek, David Nolte

Proceedings Volume 8230, Biomedical Applications of Light Scattering VI; 823006 (2012) https://doi.org/10.1117/12.907658
Event: SPIE BiOS, 2012, San Francisco, California, United States

Abstract

The detection of cellular mitosis inside three-dimensional living tissue at depths up to 1 mm has been beyond the detection limits of conventional microscopies. In this paper, we demonstrate the use of motility contrast imaging and fluctuation spectroscopy to detect motional signatures that we attribute to mitotic events within groups of 100 cells in multicellular tumor spheroids. Motility contrast imaging is a coherence-domain speckle-imaging technique that uses low-coherence off-axis holography as a coherence gate to localize dynamic light scattering from selected depths inside tissue. Fluctuation spectroscopy is performed on a pervoxel basis to generate micro-spectrograms that display frequency content vs. time. Mitosis, especially in Telophase and Cytokinesis, is a relatively fast and high-amplitude phenomenon that should display energetic features within the micro-spectrograms. By choosing an appropriate frequency range and threshold, we detect energetic events with a density and rate that are comparable to the expected mitotic fraction in the UMR cell line. By studying these mitotic events in tumors of two different sizes, we show that micro-spectrograms contain characteristically different information content than macro-spectrograms (averaged over many voxels) in which the mitotic signatures (which are overall a low-probability event) are averaged out. The detection of mitotic fraction in thick living tissue has important consequences for the use of tissue-based assays for drug discovery.

Citation Download Citation

Ran An, Kwan Jeong, John Turek, and David Nolte "Label-free mitosis detection in tumor spheroids using tissue dynamics imaging", Proc. SPIE 8230, Biomedical Applications of Light Scattering VI, 823006 (13 February 2012); https://doi.org/10.1117/12.907658

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KEYWORDS

Tumors

Tissues

Tissue optics

Imaging spectroscopy

Spectroscopy

Coherence imaging

Beam splitters

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