High Dose-Per-Fraction Irradiation of Limited Lung Volumes Using an Image-Guided, Highly Focused Irradiator: Simulating Stereotactic Body Radiotherapy Regimens in a Small-Animal Model

Jaeho Cho, Reinhard Kodym, Serguei Seliounine, James A. Richardson, Timothy D. Solberg, Michael D. Story

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Abstract

Purpose: To investigate the underlying biology associated with stereotactic body radiotherapy (SBRT), both in vivo models and image-guided, highly focal irradiation systems are necessary. Here, we describe such an irradiation system and use it to examine normal tissue toxicity in a small-animal model at lung volumes similar to those associated with human therapy. Methods and Materials: High-dose radiation was delivered to a small volume of the left lung of C3H/HeJCr mice using a small-animal stereotactic irradiator. The irradiator has a collimation mechanism to produce focal radiation beams, an imaging subsystem consisting of a fluorescent screen coupled to a charge-coupled device camera, and a manual positioning stage. Histopathologic examination and micro-CT were used to evaluate the radiation response. Results: Focal obliteration of the alveoli by fibrous connective tissue, hyperplasia of the bronchiolar epithelium, and presence of a small number of inflammatory cells are the main reactions to low-volume/high-dose irradiation of the mouse lung. The tissue response suggested a radiation dose threshold for early phase fibrosis lying between 40 and 100 Gy. The irradiation system satisfied our requirements of high-dose-rate, small beam diameter, and precise localization and verification. Conclusions: We have established an experimental model and image-guided animal irradiation system for the study of high dose per fraction irradiations such as those used with SBRT at volumes analogous to those used in human beings. It will also allow the targeting of specific anatomical structures of the thorax or ultimately, orthotopic tumors of the lung.

Original languageEnglish (US)
Pages (from-to)895-902
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume77
Issue number3
DOIs
StatePublished - 2010

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animal models
Radiosurgery
lungs
radiation therapy
Animal Models
Radiation
dosage
Lung
irradiation
mice
animals
Inbred C3H Mouse
radiation
alveoli
Connective Tissue
Hyperplasia
connective tissue
thorax
fibrosis
Fibrosis

Keywords

  • High-dose focused radiotherapy
  • Image-guided radiotherapy
  • Small-animal model
  • Stereotactic body radiotherapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

Cite this

@article{869f78b535934598ad8b941fba2bf1ee,
title = "High Dose-Per-Fraction Irradiation of Limited Lung Volumes Using an Image-Guided, Highly Focused Irradiator: Simulating Stereotactic Body Radiotherapy Regimens in a Small-Animal Model",
abstract = "Purpose: To investigate the underlying biology associated with stereotactic body radiotherapy (SBRT), both in vivo models and image-guided, highly focal irradiation systems are necessary. Here, we describe such an irradiation system and use it to examine normal tissue toxicity in a small-animal model at lung volumes similar to those associated with human therapy. Methods and Materials: High-dose radiation was delivered to a small volume of the left lung of C3H/HeJCr mice using a small-animal stereotactic irradiator. The irradiator has a collimation mechanism to produce focal radiation beams, an imaging subsystem consisting of a fluorescent screen coupled to a charge-coupled device camera, and a manual positioning stage. Histopathologic examination and micro-CT were used to evaluate the radiation response. Results: Focal obliteration of the alveoli by fibrous connective tissue, hyperplasia of the bronchiolar epithelium, and presence of a small number of inflammatory cells are the main reactions to low-volume/high-dose irradiation of the mouse lung. The tissue response suggested a radiation dose threshold for early phase fibrosis lying between 40 and 100 Gy. The irradiation system satisfied our requirements of high-dose-rate, small beam diameter, and precise localization and verification. Conclusions: We have established an experimental model and image-guided animal irradiation system for the study of high dose per fraction irradiations such as those used with SBRT at volumes analogous to those used in human beings. It will also allow the targeting of specific anatomical structures of the thorax or ultimately, orthotopic tumors of the lung.",
keywords = "High-dose focused radiotherapy, Image-guided radiotherapy, Small-animal model, Stereotactic body radiotherapy",
author = "Jaeho Cho and Reinhard Kodym and Serguei Seliounine and Richardson, {James A.} and Solberg, {Timothy D.} and Story, {Michael D.}",
year = "2010",
doi = "10.1016/j.ijrobp.2009.12.074",
language = "English (US)",
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pages = "895--902",
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T1 - High Dose-Per-Fraction Irradiation of Limited Lung Volumes Using an Image-Guided, Highly Focused Irradiator

T2 - Simulating Stereotactic Body Radiotherapy Regimens in a Small-Animal Model

AU - Cho, Jaeho

AU - Kodym, Reinhard

AU - Seliounine, Serguei

AU - Richardson, James A.

AU - Solberg, Timothy D.

AU - Story, Michael D.

PY - 2010

Y1 - 2010

N2 - Purpose: To investigate the underlying biology associated with stereotactic body radiotherapy (SBRT), both in vivo models and image-guided, highly focal irradiation systems are necessary. Here, we describe such an irradiation system and use it to examine normal tissue toxicity in a small-animal model at lung volumes similar to those associated with human therapy. Methods and Materials: High-dose radiation was delivered to a small volume of the left lung of C3H/HeJCr mice using a small-animal stereotactic irradiator. The irradiator has a collimation mechanism to produce focal radiation beams, an imaging subsystem consisting of a fluorescent screen coupled to a charge-coupled device camera, and a manual positioning stage. Histopathologic examination and micro-CT were used to evaluate the radiation response. Results: Focal obliteration of the alveoli by fibrous connective tissue, hyperplasia of the bronchiolar epithelium, and presence of a small number of inflammatory cells are the main reactions to low-volume/high-dose irradiation of the mouse lung. The tissue response suggested a radiation dose threshold for early phase fibrosis lying between 40 and 100 Gy. The irradiation system satisfied our requirements of high-dose-rate, small beam diameter, and precise localization and verification. Conclusions: We have established an experimental model and image-guided animal irradiation system for the study of high dose per fraction irradiations such as those used with SBRT at volumes analogous to those used in human beings. It will also allow the targeting of specific anatomical structures of the thorax or ultimately, orthotopic tumors of the lung.

AB - Purpose: To investigate the underlying biology associated with stereotactic body radiotherapy (SBRT), both in vivo models and image-guided, highly focal irradiation systems are necessary. Here, we describe such an irradiation system and use it to examine normal tissue toxicity in a small-animal model at lung volumes similar to those associated with human therapy. Methods and Materials: High-dose radiation was delivered to a small volume of the left lung of C3H/HeJCr mice using a small-animal stereotactic irradiator. The irradiator has a collimation mechanism to produce focal radiation beams, an imaging subsystem consisting of a fluorescent screen coupled to a charge-coupled device camera, and a manual positioning stage. Histopathologic examination and micro-CT were used to evaluate the radiation response. Results: Focal obliteration of the alveoli by fibrous connective tissue, hyperplasia of the bronchiolar epithelium, and presence of a small number of inflammatory cells are the main reactions to low-volume/high-dose irradiation of the mouse lung. The tissue response suggested a radiation dose threshold for early phase fibrosis lying between 40 and 100 Gy. The irradiation system satisfied our requirements of high-dose-rate, small beam diameter, and precise localization and verification. Conclusions: We have established an experimental model and image-guided animal irradiation system for the study of high dose per fraction irradiations such as those used with SBRT at volumes analogous to those used in human beings. It will also allow the targeting of specific anatomical structures of the thorax or ultimately, orthotopic tumors of the lung.

KW - High-dose focused radiotherapy

KW - Image-guided radiotherapy

KW - Small-animal model

KW - Stereotactic body radiotherapy

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