A deep learning model (FociRad) for automated detection of γ-H2AX foci and radiation dose estimation

DNA double-strand breaks (DSBs) are the most lethal form of damage to cells from irradiation. γ-H2AX (phosphorylated form of H2AX histone variant) has become one of the most reliable and sensitive biomarkers of DNA DSBs. However, the γ-H2AX foci assay still has limitations in the time consumed for manual scoring and possible variability between scorers. This study proposed a novel automated foci scoring method using a deep convolutional neural network based on a You-Only-Look-Once (YOLO) algorithm to quantify γ-H2AX foci in peripheral blood samples. FociRad, a two-stage deep learning approach, consisted of mononuclear cell (MNC) and γ-H2AX foci detections. Whole blood samples were irradiated with X-rays from a 6 MV linear accelerator at 1, 2, 4 or 6 Gy. Images were captured using confocal microscopy. Then, dose-response calibration curves were established and implemented with unseen dataset. The results of the FociRad model were comparable with manual scoring. MNC detection yielded 96.6% accuracy, 96.7% sensitivity and 96.5% specificity. γ-H2AX foci detection showed very good F1 scores (> 0.9). Implementation of calibration curve in the range of 0-4 Gy gave mean absolute difference of estimated doses less than 1 Gy compared to actual doses. In addition, the evaluation times of FociRad were very short (< 0.5 min per 100 images), while the time for manual scoring increased with the number of foci. In conclusion, FociRad was the first automated foci scoring method to use a YOLO algorithm with high detection performance and fast evaluation time, which opens the door for large-scale applications in radiation triage.