Description
- Abstract:
- The systemic shift in healthcare towards precision medicine has prompted the alignment of anticancer drug selection with a more individualized approach. Moreover, advancements in 3D microtissue spheroids could enable a more robust in vitro tumor model. However, the use of spheroids has been curbed by limitations in chemotherapy and resistance assays as many use staining agents and are primarily suited for 2D cultures. In utilizing its label-free, volumetric imaging capabilities, optical coherence tomography (OCT) techniques could circumvent the present limitations in traditional assays in addition to providing a means for high-throughput, functional testing of chemotherapeutic agents. As part of a long-term goal to develop and validate OCT techniques as a label-free, 3D viability assay for anticancer drug selection, the main research objectives were derived. A pilot study was conducted using HepG2 spheroids treated with ethanol as a preliminary investigation into the OCT system and metric dynamics. Significant time-dependent changes in intensity, decorrelation, and normalized decorrelation were observed. Additionally, limitations in focus shift, experiment time, spheroid region of interest selection, and metrics were identified, and improvements were implemented into the main study. The main cell viability study used neurospheroids treated with metabolism inhibitors, Oligomycin A and 2-Deoxy-D-glucose, to establish and characterize OCT metrics that are potentially sensitive to pathway-dependent viability disruptions, and specifically through targeting metabolic inhibition. Analysis of spheroid geometry, intensity, decorrelation, and normalized decorrelation metrics confirmed OCT was sensitive to different stages and pathways of cell viability disruption, although not all trends were fully palatable yet. Additionally, localized differences in intensity and decorrelation were observed, supporting the technical feasibility of OCT to detect subregion-specific drug sensitivities. Altogether, the results provide a rationale and proof of technical feasibility for further developing OCT as a label-free, 3D assay for functional precision medicine.
- Notes:
- Thesis (Sc. M.)--Brown University, 2020
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Citation
Woo, Madison,
"Label-free functional imaging of cell viability response to disruptive agents in 3D spheroids using optical coherence tomography"
(2020).
Biomedical Engineering Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.26300/czbh-0f26
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Biomedical Engineering Theses and Dissertations
Theses and Dissertations for the Biomedical Engineering department....