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Development of a small animal model to simulate clinical stereotactic body radiotherapy-induced central and peripheral lung injuries

 Zhen-Yu Hong  ;  Sung Ho Eun  ;  Kwangwoo Park  ;  Won Hoon Choi  ;  Jung Il Lee  ;  Eun-Jung Lee  ;  Ji Min Lee  ;  Michael D. Story  ;  Jaeho Cho 
 JOURNAL OF RADIATION RESEARCH, Vol.55(4) : 648-657, 2014 
Journal Title
Issue Date
Animals ; Disease Models, Animal ; Lung Injury/diagnostic imaging ; Lung Injury/etiology* ; Lung Injury/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Radiation Injuries, Experimental/diagnostic imaging ; Radiation Injuries, Experimental/etiology* ; Radiation Injuries, Experimental/pathology ; Radiosurgery/adverse effects* ; Radiosurgery/instrumentation ; Respiratory Mechanics/radiation effects ; Time Factors ; X-Ray Microtomography
SBRT ; animal model ; fibrosis ; pneumonitis
Given the tremendous potential of stereotactic body radiotherapy (SBRT), investigations of the underlying radiobiology associated with SBRT-induced normal tissue injury are of paramount importance. This study was designed to develop an animal model that simulates centrally and peripherally located clinical SBRT-induced lung injuries. A 90-Gy irradiation dose was focally delivered to the central and peripheral areas of the left mouse lung with an image-guided small-animal irradiation system. At 1, 2 and 4 weeks after irradiation, micro-computed tomography (micro-CT) images of the lung were taken. Lung function measurements were performed with the Flexivent® system (SCIREQ©, Montreal, Canada). For the histopathological analysis, the lungs were fixed by perfusing with formalin, and paraffin sections were stained with hematoxylin and eosin and Masson's Trichrome. Gross inspection clearly indicated local lung injury confined to the central and peripheral areas of the left lung. Typical histopathological alterations corresponding to clinical manifestations were observed. The micro-CT analysis results appeared to correlate with the histopathological findings. Mouse lung tissue damping increased dramatically at central settings, compared with that at the control or peripheral settings. An animal model to simulate clinical SBRT-induced central and peripheral lung injuries was developed and validated with histopathological, radiological and functional analyses. This model increases our understanding of SBRT-induced central and peripheral lung injuries and will help to improve radiation therapy in the future.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Park, Kwang Woo(박광우) ORCID logo https://orcid.org/0000-0002-9843-7985
Lee, Eun Jung(이은정)
Lee, Jung Il(이정일)
Lee, Ji Min(이지민)
Cho, Jae Ho(조재호) ORCID logo https://orcid.org/0000-0001-9966-5157
Choi, Won Hoon(최원훈)
Hong, Zhen-Yu(홍진우)
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