title: Time, Dose, and Volume Responses in a Mouse Pulmonary Injury Model Following Ablative Irradiation.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.|Department of Medical Oncology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China.
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: Chang Geol
authors.initials: CG
authors.lastname: Lee
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Hyo Sup
authors.initials: HS
authors.lastname: Shim
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: Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, 2201 Inwood Rd, Dallas, TX, 75093, USA.
authors.forename: Kwang Hyun
authors.initials: KH
authors.lastname: Song
authors.affiliation: Department of Radiology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Byoung Wook
authors.initials: BW
authors.lastname: Choi
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
authors.affiliation: Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, 2201 Inwood Rd, Dallas, TX, 75093, USA. Michael.Story@UTSouthwestern.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Story
mesh_terms: D055371:Acute Lung Injury / Q000000981:diagnostic imaging / Q000473:pathology*; D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005355:Fibrosis; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009929:Organ Size; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000000981:diagnostic imaging / Q000473:pathology*; D016634:Radiosurgery / Q000009:adverse effects; D013997:Time Factors; D055114:X-Ray Microtomography
keywords: Fibrosis; SABR; Small animal model