title: Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture.
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.
authors.affiliation: Purdue University, Department of Physics, 525 Northwestern Avenue, West Lafayette, Indiana 47907, United States.
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.affiliation: Purdue University, Department of Physics, 525 Northwestern Avenue, West Lafayette, Indiana 47907, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Merrill
authors.affiliation: Animated Dynamics, Inc., 5770 Decatur Boulevard Suite A, Indianapolis, Indiana 46241, United States.
authors.forename: Ran
authors.initials: R
authors.lastname: An
authors.affiliation: Purdue University, Department of Basic Medical Sciences, West Lafayette, 625 Harrison Street, Indiana 47907, United States.
authors.forename: John
authors.initials: J
authors.lastname: Turek
authors.affiliation: Northwestern University School of Medicine, 303 East SuperiorChicago, Illinois 60611, United States.
authors.forename: Daniela
authors.initials: D
authors.lastname: Matei
authors.affiliation: Purdue University, Department of Physics, 525 Northwestern Avenue, West Lafayette, Indiana 47907, United States.
authors.forename: David D
authors.initials: DD
authors.lastname: Nolte
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D018929:Cell Culture Techniques; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006696:Holography / Q000379:methods*; D009369:Neoplasms; D061848:Optical Imaging / Q000379:methods*; D017239:Paclitaxel / Q000494:pharmacology; D010641:Phenotype; D018874:Spheroids, Cellular / Q000187:drug effects / Q000648:ultrastructure; D046509:Tissue Culture Techniques / Q000379:methods*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel