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Time, Dose, and Volume Responses in a Mouse Pulmonary Injury Model Following Ablative Irradiation

 Zhen-Yu Hong  ;  Chang Geol Lee  ;  Hyo Sup Shim  ;  Eun Jung Lee  ;  Kwang Hyun Song  ;  Byoung Wook Choi  ;  Jaeho Cho  ;  Michael D. Story 
 LUNG, Vol.194(1) : 81-90, 2016 
Journal Title
Issue Date
Acute Lung Injury/diagnostic imaging ; Acute Lung Injury/pathology* ; Animals ; Dose-Response Relationship, Radiation ; Female ; Fibrosis ; Lung/diagnostic imaging ; Lung/pathology* ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Organ Size ; Radiation Dosage ; Radiation Injuries, Experimental/diagnostic imaging ; Radiation Injuries, Experimental/pathology* ; Radiosurgery/adverse effects ; Time Factors ; X-Ray Microtomography
Fibrosis ; SABR ; Small animal model
PURPOSE: We aimed to determine the time, dose, and volume responses in a mouse pulmonary injury model following ablative dose focal irradiation (ADFIR) in order to better understand normal lung injury. METHODS AND MATERIALS: ADFIR was administered to the left lung of mice using a small animal micro-irradiator. Histopathological evaluation and micro-computed tomography (micro-CT) analyses were performed at 1, 2, 6, and 12 weeks after irradiation. Dose responses were tested at doses of 0-90 Gy in C57BL/6 and C3H/HeJCr mice at 6 weeks after irradiation. The volume effect was evaluated with 1-, 3-, and 5-mm diameter collimators at 1-4 weeks after 90-Gy irradiation. RESULTS: ADFIR caused gross local lung injury of the inflated lung in just 1 week, with extensive hyaline material visible in the irradiated area. The fibrosing process was initiated as early as 2 weeks after irradiation. C3H and C57 mice did not show significant differences in dose response. Six weeks after irradiation, the radiation dose-response curve had a sigmoidal shape, where the lag, log, and stationary phases occurred at <40, 50-70, and >80 Gy, respectively. ADFIR induced substantial volume-dependent structural and functional damage to the lungs, and the volume changes of lung consolidation on micro-CT correlated inversely with lung fibrosis over time. CONCLUSIONS: We determined the time, dose, and volume responses in our established small animal model, and found that lung injury was substantially accelerated and phenotypically different from that of prior studies using non-ablative hemi-thorax and complete thorax irradiation schemes.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Lee, Eun Jung(이은정)
Lee, Chang Geol(이창걸) ORCID logo https://orcid.org/0000-0002-8702-881X
Cho, Jae Ho(조재호) ORCID logo https://orcid.org/0000-0001-9966-5157
Choi, Byoung Wook(최병욱) ORCID logo https://orcid.org/0000-0002-8873-5444
Hong, Zhen-Yu(홍진우)
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