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% to 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.

Doppler imaging detects bacterial infection of living tissue

“…An important application of the living tissue sentinels is to serve as a dynamic substrate for the study of antibiotic sensitivity and resistance. Previous studies of BDI in drug development and personalized medicine classified the response of living biopsy samples from patients enrolled in clinical trials into sensitive or resistant cohorts 22 . In the current microbiology context, the test samples are the immortalized DLD-1 sentinels that perform as dynamic substrates on which to observe the dynamic effects of infection and to observe how the infection responds to antibiotic treatments.…”

“…(For a detailed analysis of intracellular Doppler light scattering see ref. 19 ) BDI of living tissues has been used for drug screening 20 , for the assessment of chemoresistance for canine and human patients 21,22 , and for oocyte and embryo viability in artificial reproductive technology 23 . In this article, we describe the first application of BDI to probe subtle changes in the intracellular motions of in vitro living host tissue induced by an earlystage bacterial infection.…”

Temporal Non-Uniform Compressive Sampling for Dynamic Optical Coherence Tomography

“…Often times it is desired to contrast these dynamic features volumetrically, such as for quantitative retinal blood flow imaging [9], airway tissue surface dynamics [10], and imaging of organoid motility [11], which require high dimensional (3+1)D imaging. Even if only cross-sectional (2+1)D imaging is needed, screening applications such as personalizing cancer chemotherapies [12] and toxicant assays [13] require additional dimensions of study conditions. The development of compressive sampling techniques would be beneficial for reducing OCT scanning requirements and memory overhead, and favorable toward such high-throughput applications.…”

Temporal Non-Uniform Compressive Sampling for Dynamic Optical Coherence Tomography

“…Often times it is desired to contrast these dynamic features volumetrically, such as for quantitative retinal blood flow imaging [9], airway tissue surface dynamics [10], and imaging of organoid motility [11], which require high dimensional (3+1)D imaging. Even if only cross-sectional (2+1)D imaging is needed, screening applications such as personalizing cancer chemotherapies [12] and toxicant assays [13] require additional dimensions of study conditions. The development of compressive sampling techniques would be beneficial for reducing OCT scanning requirements and memory overhead, and favorable toward such high-throughput applications.…”