Intracellular optical doppler phenotypes of chemosensitivity in human epithelial ovarian cancer

Abstract

Development of an assay to predict response to chemotherapy has remained an elusive goal in cancer research. We report a phenotypic chemosensitivity assay for epithelial ovarian cancer based on Doppler spectroscopy of infrared light scattered from intracellular motions in living three-dimensional tumor biopsy tissue measured in vitro. The study analyzed biospecimens from 20 human patients with epithelial ovarian cancer. Matched primary and metastatic tumor tissues were collected for 3 patients, and an additional 3 patients provided only metastatic tissues. Doppler fluctuation spectra were obtained using full-field optical coherence tomography through off-axis digital holography. Frequencies in the range from 10 mHz to 10 Hz are sensitive to changes in intracellular dynamics caused by platinum-based chemotherapy. Metastatic tumor tissues were found to display a biodynamic phenotype that was similar to primary tissue from patients who had poor clinical outcomes. The biodynamic phenotypic profile correctly classified 90% [88–91% c.i.] of the patients when the metastatic samples were characterized as having a chemoresistant phenotype. This work suggests that Doppler profiling of tissue response to chemotherapy has the potential to predict patient clinical outcomes based on primary, but not metastatic, tumor tissue.

Patient-derived cancer organoid tracking with wide-field one-photon redox imaging to assess treatment response

“…11,47 Diameter measurements are also limited because changes in PCO diameter or morphology often lag behind functional changes. [69][70][71][72] Here we provide the first demonstration of wide-field one-photon redox imaging for functional assessment of drug response in PCOs. Redox imaging improves on existing tools for PCO screening as it is non-destructive, rapid, and label-free, requiring no additional dyes or reagents.…”

Coherent light scattering from cellular dynamics in living tissues

“…The resistant phenotype is dominated by a mid-frequency enhancement, while the sensitive dogs were more likely to display a mid-frequency suppression with enhance organelle and membrane activities that are representative of apoptosis [401]. A similar study was completed for human ovarian cancer patients [396] and human bladder cancer patients [397]. In both studies, TDS signatures were found to be correlated with patient outcomes.…”

“…It has also been applied to studies of plasma flow [385,386], dermatology [387], eye drainage [388], and embryology [389][390][391]. For potential use for drug development and diagnostics, dynamic OCT has been used to characterize three-dimensional tissue culture [383,392,393], and for testing chemotherapy cancer drug efficacy in animal preclinical trials [394,395] and in human clinical trials [396,397]. Some of these applications are highlighted in figure 33.…”

Classifying tumor heterogeneity of human esophageal cancer biopsies by dynamic contrast OCT with deep learning

“…The highly variable character of OCT tissue dynamics spectra among the biopsy samples for a single patient presents an ideal opportunity for deep learning. Our previous work on tissue dynamics of cancer biopsies 5 used averaging approaches which suppressed the conditional dependences. Here, we retain the full well-to-well variability.…”