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Updated: Jul 17, 2026
Multiparametric Tumor Organoid Drug Screening Using Widefield Live-Cell Imaging for Bulk and Single-Organoid Analysis
Published on: December 23, 2022
Longitudinal drug response assessment of tumor organoids based on optical attenuation coefficient and
Shanshan Yang1,2, Jing Guo1, Wanli Wang1
1School of Automation, Hangzhou Dianzi University, Hangzhou, Zhejiang 310018, China.
Abstract:
Patient-derived tumor organoids (PDTOs) are vital for precision oncology, but standard drug screening methods, including adenosine triphosphate (ATP) assays, are destructive and prevent longitudinal monitoring. Optical coherence tomography (OCT) offers non-destructive 3D imaging, capturing morphological features and tissue attenuation characteristics via the optical attenuation coefficient (OAC). Here, we propose a non-destructive evaluation framework for tumor organoids that fuses OAC and multi-dimensional morphological features. Using intrahepatic cholangiocarcinoma (iCCA) PDTOs treated with icaritin, we found that OAC exhibited a significant dose-dependent increase (up to 32.8% at 80 μM compared to control), accompanied by a morphological transition of cystic organoids into solid phenotypes. By integrating these features via K-means++ clustering and principal component analysis, we constructed a relative growth score. This fusion score correlated strongly with the ATP gold standard (Pearson correlation coefficient r = 0.938), outperforming a morphology-only model (r = 0.906). Furthermore, independent experiments with first-line chemotherapeutics (e.g., 5-Fluorouracil, Gemcitabine) and combinatorial regimens indicated the model's potential generalizability (r = 0.887). This method overcomes the limitations of destructive, single-metric evaluations, providing a quantitative and non-destructive platform for high-throughput drug screening and personalized treatment decision-making.
Insights
This study introduces a non-destructive method using Optical Coherence Tomography to evaluate tumor organoids for precision oncology. The new framework accurately predicts drug response, overcoming limitations of current destructive assays.
Area of Science:
- Biomedical Imaging
- Oncology
- Drug Discovery
Background:
- Patient-derived tumor organoids (PDTOs) are crucial for precision oncology.
- Current drug screening methods, like ATP assays, are destructive and limit longitudinal studies.
- Optical Coherence Tomography (OCT) provides non-destructive 3D imaging and quantitative tissue properties.
Purpose of the Study:
- To develop a non-destructive evaluation framework for PDTOs.
- To integrate Optical Attenuation Coefficient (OAC) and morphological features for drug response assessment.
- To enable longitudinal monitoring and high-throughput drug screening in oncology.
Main Methods:
- Utilized OCT to capture OAC and morphological data from intrahepatic cholangiocarcinoma (iCCA) PDTOs treated with icaritin.
- Fused OAC and morphological features using K-means++ clustering and Principal Component Analysis to create a relative growth score.
- Validated the framework against ATP assays and tested generalizability with standard chemotherapeutics (5-Fluorouracil, Gemcitabine).
Main Results:
- OAC significantly increased with icaritin dose, correlating with a shift from cystic to solid organoid phenotypes.
- The fused feature score showed a strong correlation with ATP assay results (r=0.938), outperforming morphology-only analysis (r=0.906).
- The model demonstrated good generalizability with other chemotherapeutics (r=0.887).
Conclusions:
- The proposed non-destructive framework effectively assesses PDTO response to drugs.
- This method overcomes limitations of destructive assays, enabling quantitative, longitudinal monitoring.
- The technology supports high-throughput drug screening and aids personalized treatment decisions in oncology.
