基于CT参数分析模型评估辐射诱导小鼠肺纤维化剂量-效应关系研究

摘要

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.%目的 基于肺纤维化影像学改变建立剂量-效应模型,定量分析辐射剂量与诱导肺纤维化间的关系.方法 8～10周龄C57BL6雌性小鼠随机分组接受单次20 Gy X线照射.照射前后不同时间点行CT扫描成像,图像经三维分割算法获得影像学肺密度与肺部体积值定量参数.经梯度剂量X线照射后,基于基因芯片与病理学验证后对CT参数进行逻辑回归建模.结果 20 Gy照射后24周受照鼠肺密度较空白对照组显著增加[(-289.81±12.06) HU ∶ (-377.97±6.24) HU,P<0.001].照射组小鼠平均肺体积较对照组明显缩小[(0.44±0.03) cm3 ∶ (0.66±0.01) cm3,P<0.001)].影像学定量分析结果与HE及Masson染色法观察到的肺纤维化结果相符,与肺纤维化基因标志物转录表达水平呈正相关( R2=0.75,P<0.001).经逻辑回归建模得到辐射诱导肺密度增加的剂量为( 13.64±0.14) Gy ( R2=0.99,P<0.001);引起肺体积减小的剂量为(16.17±4.36) Gy (R2=0.89,P<0.001).结论 CT肺密度与肺体积定量分析可作为评估小鼠放射性肺纤维化程度的可靠影像学参数,肺纤维化影像学改变剂量-效应模型可为进一步比较肺部大剂量低分割照射及半肺野照射致肺纤维化研究提供实验基础.