Gil Daniel A, Deming Dustin A, Skala Melissa C
Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53704, USA.
Morgridge Institute for Research, Madison, WI 53704, USA.
Biomed Opt Express. 2021 Jun 3;12(7):3789-3805. doi: 10.1364/BOE.428197. eCollection 2021 Jul 1.
Patient-derived cancer organoids (PCOs) are organotypic models that reflect 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.
患者来源的癌症类器官（PCOs）是反映药物反应的器官型模型，因此PCOs是在临床相关时间范围内进行癌症药物筛选的一种可及模型。然而，目前评估PCOs反应的方法有限。在此，使用定制的扫频光学相干断层扫描（OCT）系统来快速评估PCOs的体积生长和药物反应。该系统针对倒置成像几何结构进行了优化，以实现PCOs的高通量成像。开发了一个自动图像分析框架，用于在48小时内对多个时间点的PCOs进行三维单类器官跟踪。与对照PCOs相比，代谢抑制剂和癌症疗法降低了PCOs的体积生长速率。与对类器官体积变化的汇总分析相比，单类器官跟踪提高了对药物治疗的敏感性。与基于二维投影的体积估计方法相比，OCT对类器官体积的评估更准确。使用OCT进行单类器官跟踪还发现了实体和空心PCOs之间药物反应的异质性。这项工作表明，OCT和三维单类器官跟踪是监测PCOs体积生长和药物反应的有吸引力的工具，提供了快速、无损的方法来量化PCOs中的异质性。
