Quantifying the drug response of patient-derived organoid clusters by aggregated morphological indicators with multi-parameters based on optical coherence tomography.

Abstract

Patient-derived organoids (PDOs) serve as excellent tools for personalized drug screening to predict clinical outcomes of cancer treatment. However, current methods for efficient quantification of drug response are limited. Herein, we develop a method for label-free, continuous tracking imaging and quantitative analysis of drug efficacy using PDOs. A self-developed optical coherence tomography (OCT) system was used to monitor the morphological changes of PDOs within 6 days of drug administration. OCT image acquisition was performed every 24 h. An analytical method for organoid segmentation and morphological quantification was developed based on a deep learning network (EGO-Net) to simultaneously analyze multiple morphological organoid parameters under the drug's effect. Adenosine triphosphate (ATP) testing was conducted on the last day of drug treatment. Finally, a corresponding aggregated morphological indicator (AMI) was established using principal component analysis (PCA) based on the correlation analysis between OCT morphological quantification and ATP testing. Determining the AMI of organoids allowed quantitative evaluation of the PDOs responses to gradient concentrations and combinations of drugs. Results showed that there was a strong correlation (correlation coefficient >90%) between the results using the AMI of organoids and those from ATP testing, which is the standard test used for bioactivity measurement. Compared with single-time-point morphological parameters, the introduction of time-dependent morphological parameters can reflect drug efficacy with improved accuracy. Additionally, the AMI of organoids was found to improve the efficiency of 5-fluorouracil(5FU) against tumor cells by allowing the determination of the optimum concentration, and the discrepancies in response among different PDOs using the same drug combinations could also be measured. Collectively, the AMI established by OCT system combined with PCA could quantify the multidimensional morphological changes of organoids under the drug's effect, providing a simple and efficient tool for drug screening in PDOs.