正常肺组织大分割照射全肺平均耐受剂量与生物学效应研究

Normal lung tissue response following hypofractionated radiation based on radiological parameters

目的建立正常组织分次照射基于肺纤维化影像学改变的全肺平均剂量-效应模型,定量分析分割照射相比单次照射的生物学效应及耐受剂量关系.方法采用8~10周龄C57BL6雌性小鼠按随机数表法分组进行X射线全肺野照射,分别给予梯度剂量0、2.0Gy×5次、4.0Gy×5次、6.0Gy×5次、7.0Gy×5次、8.5Gy×5次.照射后24周行CT扫描成像,CT图像三维重建后经三维分割算法获得肺部平均密度与肺部体积值,并分别据此进行Boltzmann模型放射生物学建模.结果照射后24周CT图像三维重建冠状位图像提示剂量依赖的肺部影像学改变.同一时间点肺组织全基因组芯片与组织病理学研究均提示与影像学改变高度吻合.经放射生物学建模,分次照射诱导肺密度改变的全肺平均剂量(Dmean)中位剂量为(30.80±0.80)Gy(校正R2=0.97);引起肺体积减小的中位剂量为(31.31±7.07)Gy(校正R2=0.92).基于影像学参数的剂量-效应曲线提示,肺组织对分次照射的耐受性相比单次照射显著提高.结论纤维化进展过程中,肺密度与肺体积改变对X射线的依赖性不仅取决于总剂量大小,也与分割次数、分次剂量存在一定关联.

Objective To study dose-response relationships of fractionated irradiation induced pulmonary fibrosis in mice according to radiological imaging changes of lung. Methods A total of 8-10 week old-female C57BL6 mice were randomized into different groups for whole thoracic irradiation. The prescribed doses were 0, 2.0, 4.0, 6.0, 7.0, 8.5 Gy per fraction in a total of 5 fractions. CT imaging was performed at 24 weeks post irradiation. The averaged lung density and volume changes were obtained by the three-dimensional segmentation algorithm, and further analyzed in Boltzmann regression modeling. Results At the endpoint of 24 weeks, the dose-dependent pulmonary radiological alternations were revealed by coronal view of CT images. Translational analysis of fibrosis-related gene-signatures as well as histological collagen stainings further corroborated the radiological findings. According to Boltzmann modeling, the E50 of radiation-induced lung density changes was found to be (30.80±0.80)Gy (adjusted R2=0.97);whereas the E50 for radiation-induced lung volume reduction was determined as (31.31±7.07)Gy (adjusted R2=0.92). Both outcomes indicated a remarkable enhancement of tolerance to normal lung tissues after exposure with 5-fraction versus single fraction scheme. Conclusions The radiation-induced lung density and volume changes depend not only on total dose, but also the number and dose of fractions.