title: Development of a small animal model to simulate clinical stereotactic body radiotherapy-induced central and peripheral lung injuries.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Hong
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Eun
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
authors.forename: Kwangwoo
authors.initials: K
authors.lastname: Park
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
authors.forename: Won Hoon
authors.initials: WH
authors.lastname: Choi
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
authors.forename: Jung Il
authors.initials: JI
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Story
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea jjhmd@yuhs.ac.
authors.forename: Jaeho
authors.initials: J
authors.lastname: Cho
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D055370:Lung Injury / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011833:Radiation Injuries, Experimental / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D016634:Radiosurgery / Q000009:adverse effects* / Q000295:instrumentation; D015656:Respiratory Mechanics / Q000528:radiation effects; D013997:Time Factors; D055114:X-Ray Microtomography
keywords: SBRT; animal model; fibrosis; pneumonitis