Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture

Hao Sun; Daniel Merrill; Ran An; John Turek; Daniela Matei; David D. Nolte

doi:10.1117/1.JBO.22.1.016007

9 January 2017 Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture

Hao Sun, Daniel Merrill, Ran An, John Turek, Daniela Matei, David D. Nolte

Author Affiliations +

Journal of Biomedical Optics, Vol. 22, Issue 1, 016007 (January 2017). https://doi.org/10.1117/1.JBO.22.1.016007

Abstract

Three-dimensional (3-D) tissue culture represents a more biologically relevant environment for testing new drugs compared to conventional two-dimensional cancer cell culture models. Biodynamic imaging is a high-content 3-D optical imaging technology based on low-coherence interferometry and digital holography that uses dynamic speckle as high-content image contrast to probe deep inside 3-D tissue. Speckle contrast is shown to be a scaling function of the acquisition time relative to the persistence time of intracellular transport and hence provides a measure of cellular activity. Cellular responses of 3-D multicellular spheroids to paclitaxel are compared among three different growth techniques: rotating bioreactor (BR), hanging-drop (HD), and nonadherent (U-bottom, UB) plate spheroids, compared with ex vivo living tissues. HD spheroids have the most homogeneous tissue, whereas BR spheroids display large sample-to-sample variability as well as spatial heterogeneity. The responses of BR-grown tumor spheroids to paclitaxel are more similar to those of ex vivo biopsies than the responses of spheroids grown using HD or plate methods. The rate of mitosis inhibition by application of taxol is measured through tissue dynamics spectroscopic imaging, demonstrating the ability to monitor antimitotic chemotherapy. These results illustrate the potential use of low-coherence digital holography for 3-D pharmaceutical screening applications.

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Hao Sun, Daniel Merrill, Ran An, John Turek, Daniela Matei, and David D. Nolte "Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture," Journal of Biomedical Optics 22(1), 016007 (9 January 2017). https://doi.org/10.1117/1.JBO.22.1.016007

Received: 12 September 2016; Accepted: 28 November 2016; Published: 9 January 2017

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KEYWORDS

Tissues

3D image processing

Tissue optics

Tumors

Profiling

3D metrology

Biopsy

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