Intracellular optical doppler phenotypes of chemosensitivity in human epithelial ovarian cancer

Zhe Li,Wendy M. Swetzig,Ran An,Margaux Kanis,John Turek,David Nolte,Daniela Matei,Nkechiyere Nwani

doi:10.1038/s41598-020-74336-x

Zhe Li, Wendy M. Swetzig + Show 6 more

Open Access

https://doi.org/10.1038/s41598-020-74336-x

Copy DOI

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.

Highlights

Development of an assay to predict response to chemotherapy has remained an elusive goal in cancer research
A Doppler fluctuation spectroscopy approach to chemosensitivity testing, called biodynamic imaging (BDI), was developed as the first coherence-domain imaging technique to use intracellular motion as functional image contrast[8]
Biodynamic imaging is a form of full-frame optical coherence tomography (FF-OCT)[17,18] based on off-axis digital holography that uses principles of coherent laser ranging that can quantify the dynamic response of tumors to chemotherapy treatment[19]

Summary

Introduction

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. 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. A need exists for a phenotypic assay that maintains the three-dimensional microenvironment and tests the functional response of living tissue to selected therapies To meet this need, a Doppler fluctuation spectroscopy approach to chemosensitivity testing, called biodynamic imaging (BDI), was developed as the first coherence-domain imaging technique to use intracellular motion as functional image contrast[8]. The work presented here is the first application of BDI to naturally-occurring cancer in human patients

Methods

Results

Conclusion