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.
OBJECTIVE
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
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.
Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75093, USA.
Jaeho
J
Cho
Reinhard
R
Kodym
Serguei
S
Seliounine
James A
JA
Richardson
Timothy D
TD
Solberg
Michael D
MD
Story
D000818:Animals; D001980:Bronchi / Q000473:pathology / Q000528:radiation effects; D003251:Constriction, Pathologic / Q000473:pathology; D019583:Dose Fractionation, Radiation; D004867:Equipment Design; D006801:Humans; D008168:Lung / Q000473:pathology / Q000601:surgery*; D051379:Mice; D008809:Mice, Inbred C3H; D011650:Pulmonary Alveoli / Q000473:pathology / Q000528:radiation effects; D001261:Pulmonary Atelectasis / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology; D011833:Radiation Injuries, Experimental / Q000473:pathology*; D016634:Radiosurgery / Q000295:instrumentation / Q000379:methods*