放射性肺炎是影响胸部肿瘤放疗及预后关键因素。开展动物模型研究是临床防治、新药研发、质子重离子剂量效应的重要工具；但目前国内外仍缺乏可精准量化评价小鼠肺炎的手段。我们前期研究发现：小鼠单次20Gy全肺X线照射后8~12周，虽肺部CT图像对小鼠肺炎无诊断价值，但借助计算机辅助诊断技术转换为像素热图后，可观察到明显“右移”现象；而此时正是显著炎症反应阶段，据此我们推测两者存在一定的相关性。本课题①拟用X线单次及多次分割照射方式建立小鼠肺炎模型，在照射后不同时间点跟踪获取CT图像，并尝试将“右移”现象转化为定量指标即“肺炎指数（PI）”，从而建立定量、无偏倚前临床肺炎评估手段；②在组织、转录、蛋白水平对PI的正确性进行验证及统计学分析，最终建立肺炎剂量-效应生物学预测模型及关键参数计算（α/β，ED50，BED阈剂量）；在此基础上定量比较大剂量低分割（立体定向）肺癌放疗致肺炎风险与剂量的耐受关系。

Normal lung tissue tolerance constitutes a limiting factor in delivering the required dose of radiotherapy to cure thoracic and chest wall malignancies. Radiation-induced lung injury (RILI) is considered the most critical determinant for estimating the late normal tissue complication probability (NTCP). Despite of RILI was extensively studied in past decades, neither standard criterion nor objective staging/scoring systems is available for preclinical models. This study aims to establish an unbiased and consensus evaluation to predicting pneumonitis development in vivo based on computer-assisted radiology. The preclinical C57BL/6 mouse model was established based on single and fractionated whole thoracic irradiation. A comprehensive longitudinal monitoring program will be performed on the basis of low dose CT imaging protocol by clinical CT. The pneumonitis index (PI) is to be determined utilizing CT histogram analysis based on 3D segmentation of the lungs. Intra-comparisons of PIs versus additional readouts known to be solid metrics (e.g., histopathology, transcriptional and molecular responses) were statistically analyzed. A systematic radiobiological characterization of RILI in the C57BL/6 mouse will be eventually established, with a panel of key parameters (e.g., α/β, ED50, threshold BED) to be determined. ..Characterized by intensified deposition of radiation doses, hypofractionated stereotactic body radiotherapy (SBRT) is increasingly used for early stage non-small cell lung cancer (NSCLC) and oligometastatic diseases. The present project marks an important step towards quantitative tolerance dose analysis and precise risk estimation for development of pneumonitis. In addition, the establish of PI will also facilitate mechanistic studies and novel drugs development in pneumonitis.