Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture

Abstract

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 highcontent 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.

Imaging intracellular motion with dynamic micro-optical coherence tomography

“…While intact tissue is an excellent substrate for d-µOCT, this technique could also be of great use for additional assays including two-and three-dimensional cell culture, spheroids, organoids, and organs-on-chips, among others [3,8,[26][27][28][29]. The advantage of d-µOCT as a cell viability assay would be the ability to determine the metabolic or pathobiologic state of cells in these platforms without destroying the sample for viability staining or cell-type characterization.…”

Intracellular optical doppler phenotypes of chemosensitivity in human epithelial ovarian cancer

“…By penetrating volumetrically into tissue up to 1 mm deep, BDI maps out heterogeneous tissue layers. BDI has previously been applied to drug screening 20 – 22 , phenotypic profiling 23 , and preclinical chemosensitivity testing on ovarian xenografts in mice and canine B-cell lymphoma 19 , 24 , 25 . Light scattering of near-infrared light from living ex vivo tissue biopsies displays Doppler frequency shifts caused by intracellular motion 9 .…”

“…By penetrating volumetrically into tissue up to 1 mm deep, BDI maps out heterogeneous tissue layers. BDI has previously been applied to drug screening [20][21][22] , phenotypic profiling 23 , and preclinical chemosensitivity testing on ovarian…”

Intracellular Optical Doppler Phenotypes of Chemosensitivity in Human Epithelial Ovarian Cancer

“…By penetrating volumetrically into tissue up to 1 mm deep, BDI maps out heterogeneous tissue layers. BDI has previously been applied to drug screening [20][21][22] , phenotypic profiling 23 , and preclinical chemosensitivity testing on ovarian xenografts in mice and canine B-cell lymphoma 19,24,25 . Light scattering of near-infrared light from living ex vivo tissue biopsies displays Doppler frequency shifts caused by intracellular motion 9 .…”