Design, construction, and in vivo feasibility of a positioning device for irradiation of mice brains using a clinical linear accelerator and intensity modulated radiation therapy

Abstract

Purpose: The goal of this study was to design a positioning device that would allow for selective irradiation of the mouse brain with a clinical linear accelerator.

Methods: We designed and fabricated an immobilization fixture that incorporates three functions: head stabilizer (through ear bars and tooth bar), gaseous anesthesia delivery and scavenging, and tissue mimic/bolus. Cohorts of five mice were irradiated such that each mouse in the cohort received a unique dose between 1000 and 3000 cGy. DNA damage immunohistochemistry was used to validate an increase in biological effect as a function of radiation dose. Mice were then followed with hematoxylin and eosin (H&E) and anatomical magnetic resonance imaging (MRI).

Results: There was evidence of DNA damage throughout the brain proportional to radiation dose. Radiation-induced damage at the prescribed doses, as depicted by H&E, appeared to be constrained to the white matter consistent with radiological observation in human patients. The severity of the damage correlated with the radiation dose as expected.

Conclusions: We have designed and manufactured a device that allows us to selectively irradiate the mouse brain with a clinical linear accelerator. However, some off-target effects are possible with large prescription doses.

Keywords:

• Radiation-induced brain injury
• mouse models
• small animal irradiation
• whole-brain irradiation

Acknowledgements

The authors thank and acknowledge Steve Powers from Purdue Research Machining Services for helping design and construct the positioning device. The authors acknowledge the assistance of the Purdue University Histology Laboratory, a core facility of the NIH-funded Indiana Clinical and Translational Science Institute, for the processing of the tissue sections and H&E staining.

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes on contributors

Dr. Nicholas J. Rancilio, DVM is a Clinical Assistant Professor of Radiation Oncology in the Department of Veterinary Clinical Sciences in the Purdue University College of Veterinary Medicine. He is a diplomate of the ACVR in Radiation oncology.

Mr. Shaun Dahl, MS was a trainee in the Medical Physics program in the School of Health Sciences at Purdue University. He has since graduated and has now entered residency for Medical Physics.

Dr. Ilektra Athanasiadi, DVM is a resident in Radiation Oncology in the Department of Veterinary Clinical Sciences in the Purdue University College of Veterinary Medicine.

Dr. Carlos J. Perez-Torres, is an Assistant Professor of Radiological Health Sciences within the School of Health Sciences at Purdue University. His research focuses on the use of MRI to track radiation-induced pathologies.