Tissue dynamics spectroscopy for phenotypic profiling of drug effects in three-dimensional culture

Abstract

Coherence-gated dynamic light scattering captures cellular dynamics through ultra-low-frequency (0.005–5 Hz) speckle fluctuations and Doppler shifts that encode a broad range of cellular and subcellular motions. The dynamic physiological response of tissues to applied drugs is the basis for a new type of phenotypic profiling for drug screening on multicellular tumor spheroids. Volumetrically resolved tissue-response fluctuation spectrograms act as fingerprints that are segmented through feature masks into high-dimensional feature vectors. Drug-response clustering is achieved through multidimensional scaling with simulated annealing to construct phenotypic drug profiles that cluster drugs with similar responses. Hypoxic vs. normoxic tissue responses present two distinct phenotypes with differentiated responses to environmental perturbations and to pharmacological doses.

Quantitative Phase Imaging for Label-Free Analysis of Cancer Cells—Focus on Digital Holographic Microscopy

“…Consequently, a successful analysis of individual cells will require some degree of automation. Cellular and tissue dynamics were measured nearly ten years ago by studying speckle fluctuations caused by cellular and sub-cellular motions [94,95], and several studies have since investigated the characterization and separation of blood cells [96,97]. Abnormalities of erythrocytes are important markers for disease.…”

Development and Application of Optical Coherence Tomography (OCT)

“…Such combinations may not only improve the contrast for vascular tissue components but also provide additional, complementary insight into disease patterns [30,103,105,106]. In order to perform PS-OCT beneath the body surface, endoscopic and needle-based PS-OCT was developed [28,29,[107][108][109][110][111][112]. To further increase the contrast and image range, PS-OCT has been combined with other technologies such as ultrasound and fluorescence imaging [113,114].…”

“…Several groups also successfully studied PS-OCT for imaging breast cancer [112,186,187]. Figure 8 shows exciting results of PS-OCT imaging, which enabled the differentiation of tumor from surrounding tissue.…”

Biodynamic imaging of live porcine oocytes, zygotes and blastocysts for viability assessment in assisted reproductive technologies

“…Tissue dynamics spectroscopy [23,24] separates the motion into frequency bands related to Doppler frequencies of the scattered light. It has been used extensively in applications related to phenotypic drug discovery [23,25,26].…”