Volumetric growth tracking of patient-derived cancer organoids using optical coherence tomography.

Patient-derived cancer organoids (PCOs) are in vitro organotypic models that reflect in vivo drug response, thus PCOs are an accessible model for cancer drug screening in a clinically relevant timeframe. However, current methods to assess the response of PCOs are limited. Here, a custom swept-source optical coherence tomography (OCT) system was used to rapidly evaluate volumetric growth and drug response in PCOs. This system was optimized for an inverted imaging geometry to enable high-throughput imaging of PCOs. An automated image analysis framework was developed to perform 3D single-organoid tracking of PCOs across multiple time points over 48 hours. Metabolic inhibitors and cancer therapies decreased PCOs volumetric growth rate compared to control PCOs. Single-organoid tracking improved sensitivity to drug treatment compared to a pooled analysis of changes in organoid volume. OCT provided a more accurate assessment of organoid volume compared to a volume estimation method based on 2D projections. Single-organoid tracking with OCT also identified heterogeneity in drug response between solid and hollow PCOs. This work demonstrates that OCT and 3D single-organoid tracking are attractive tools to monitor volumetric growth and drug response in PCOs, providing rapid, non-destructive methods to quantify heterogeneity in PCOs.