Correlation of OCT-Based Radiomic Signatures With Dose-Associated Radiation Response in Tumor Spheroids

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Abstract Background Three-dimensional tumor spheroids are an established radiobiology model, but scalable, reproducible readouts of dose-dependent radiation response are lacking. We evaluated whether optical coherence tomography (OCT) radiomics can quantify dose-associated response in spheroids, and how it compares with conventional brightfield morphology. Methods This in vitro, cross-sectional study used SAS oral squamous cell carcinoma spheroids seeded at two densities (5000 and 10000 cells), irradiated at 0 to 12 Gy, and imaged on days 1 to 11 post-irradiation. Each OCT acquisition yielded co-registered structural-intensity and speckle-variance volumes. Radiomic features (shape, first-order, texture) were extracted with Radiomics.jl, filtered for repeatability, correlation-pruned, and ensemble-ranked. Dose correlation was assessed by repeated 5-fold cross-validation across five regressors, comparing brightfield-only (BF), OCT-only, and combined OCT+BF feature sets with paired Wilcoxon tests. Results OCT-only models consistently outperformed the BF baseline (median R 2 0.77 to 0.85 versus 0.61 to 0.69; p < 0.001 for all regressors). Adding brightfield to OCT gave no consistent benefit, reaching significance only for Random Forest ( p = 0.026 , power 0.62). A compact shared feature subset combined brightfield area dynamics with OCT texture, shape, and speckle-variance descriptors, all showing low repeat-scan variability relative to cohort variability. Conclusions OCT radiomics provides a sensitive, reproducible, label-free high-throughput readout of spheroid radiation dose response that outperforms the current brightfield-based approach, without requiring concurrent brightfield acquisition. Key points OCT radiomics quantifies dose-dependent radiation response in 3D tumor spheroids. OCT-only models outperformed brightfield imaging in radiation dose prediction. Selected radiomic features showed high repeatability across repeated acquisitions. Adding brightfield to OCT gave no consistent performance benefit. Label-free OCT enables reproducible, high-throughput spheroid radiation-response assessment.

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