Dose-response relationship of radiation-induced pulmonary fibrosis in mouse models based on CT-derived parameters

Objective To investigate the radiation induced pulmonary fibrosis with a dose-response mouse model, based on the CT image changes of pulmonary fibrosis. Methods Female C57BL6 mice aged 8-10 weeks were randomly divided into 20 Gy or escalated doses of X-ray whole thoracic irradiation (WTI) groups. CT scan was performed at different time points before and after radiation. The average lung density and lung volume changes were obtained by three-dimensional segmentation algorithm. After gene chip and pathological validation, the parameters of CT scan were subject to the establishment of logistic regression model. Results At the endpoint of 24 weeks post-irradiation, the lung density in the 20 Gy irradiation group was (-289.81±12.06) HU, significantly increased compared with (-377.97±6.24) HU in the control group (P<0.001). The lung volume was (0.66±0.01) cm3 in the control group, significantly larger than (0.44±0.03) cm3 in the irradiated mice (P<0.001). The results of quantitative imaging analysis were in accordance with the findings of HE and Mason staining, which were positively correlated with the fibrosis-related biomarkers at the transcriptional level (all R2=0.75, all P<0.001). The ED50 for increased lung density was found to be (13.64±0.14) Gy (R2=0.99, P<0.001) and (16.17±4.36) Gy (R2=0.89, P<0.001) for decreased lung volume according to the logistic regression model. Conclusions Quantitative CT measurement of lung density and volume are reliable imaging parameters to evaluate the degree of radiation-induced pulmonary fibrosis in mouse models. The dose-response mouse models with pulmonary fibrosis changes can provide experimental basis for comparative analysis of high-dose hypofractioned irradiation-and half-lung irradiation-induced pulmonary fibrosis. Key words: Radiation-induced lung fibrosis; Radiological assessment; Radiobiology; Dose-response effect; Mouse