Physics · Biology · Technique
Dose-response relationship of radiation-induced pulmonary fibrosis in mouse models based on CT-derived parameters
Meijuan Zhou, Zhaoming Zhou, Lei Wen, Hao Liu, Liji Cao, Shun Lu, Ziyao Li, Zhouguang Hui, Linbo Cai, Ming Chen, Longhua Chen, Cheng Zhou
Published 2019-08-15
Cite as Chin J Radiat Oncol, 2019, 28(8): 601-605. DOI: 10.3760/cma.j.issn.1004-4221.2019.08.010
Abstract
ObjectiveTo investigate the radiation induced pulmonary fibrosis with a dose-response mouse model, based on the CT image changes of pulmonary fibrosis.
MethodsFemale 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.
ResultsAt 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.
ConclusionsQuantitative 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
Contributor Information
Meijuan Zhou
Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou 510515, China
Zhaoming Zhou
Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou 510515, China
Lei Wen
Department of Oncology, Guangdong Sanjiu Brain Hospital, Guangzhou 510510, China
Hao Liu
Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou 510515, China
Liji Cao
Inviscan SAS, France Strasbourg 67200
Shun Lu
Department of Radiation Oncology, Sichuan Cancer Hospital &
Institute, University of Electronic Science and Technology of China, Chengdu 610041, China
Ziyao Li
Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
Zhouguang Hui
Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing 100021, China
Linbo Cai
Department of Oncology, Guangdong Sanjiu Brain Hospital, Guangzhou 510510, China
Ming Chen
Zhejiang Key Lab of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China
Longhua Chen
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
Cheng Zhou
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China