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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)81-90
Number of pages10
JournalLung
Volume194
Issue number1
DOIs
Publication statusPublished - 2016 Feb 1

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Lung Injury
Lung
Inbred C3H Mouse
Thorax
Tomography
Hyalin
Fibrosis
Animal Models
Radiation

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine

Cite this

Hong, Z. Y., Lee, C. G., Shim, H. S., Lee, E. J., Song, K. H., Choi, B. W., ... Story, M. D. (2016). Time, Dose, and Volume Responses in a Mouse Pulmonary Injury Model Following Ablative Irradiation. Lung, 194(1), 81-90. https://doi.org/10.1007/s00408-015-9825-4
Hong, Zhen Yu ; Lee, Chang Geol ; Shim, Hyo Sup ; Lee, Eun Jung ; Song, Kwang Hyun ; Choi, Byoung Wook ; Cho, Jaeho ; Story, Michael D. / Time, Dose, and Volume Responses in a Mouse Pulmonary Injury Model Following Ablative Irradiation. In: Lung. 2016 ; Vol. 194, No. 1. pp. 81-90.
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abstract = "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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Hong, ZY, Lee, CG, Shim, HS, Lee, EJ, Song, KH, Choi, BW, Cho, J & Story, MD 2016, 'Time, Dose, and Volume Responses in a Mouse Pulmonary Injury Model Following Ablative Irradiation', Lung, vol. 194, no. 1, pp. 81-90. https://doi.org/10.1007/s00408-015-9825-4

Time, Dose, and Volume Responses in a Mouse Pulmonary Injury Model Following Ablative Irradiation. / Hong, Zhen Yu; Lee, Chang Geol; Shim, Hyo Sup; Lee, Eun Jung; Song, Kwang Hyun; Choi, Byoung Wook; Cho, Jaeho; Story, Michael D.

In: Lung, Vol. 194, No. 1, 01.02.2016, p. 81-90.

Research output: Contribution to journalArticle

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AU - Hong, Zhen Yu

AU - Lee, Chang Geol

AU - Shim, Hyo Sup

AU - Lee, Eun Jung

AU - Song, Kwang Hyun

AU - Choi, Byoung Wook

AU - Cho, Jaeho

AU - Story, Michael D.

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N2 - 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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