title: Development and Validation of a Small Animal Immobilizer and Positioning System for the Study of Delivery of Intracranial and Extracranial Radiotherapy Using the Gamma Knife System.
abstract: The purpose of this research is to establish a process of irradiating mice using the Gamma Knife as a versatile system for small animal irradiation and to validate accurate intracranial and extracranial dose delivery using this system. A stereotactic immobilization device was developed for small animals for the Gamma Knife head frame allowing for isocentric dose delivery. Intercranial positional reproducibility of a reference point from a primary reference animal was verified on an additional mouse. Extracranial positional reproducibility of the mouse aorta was verified using 3 mice. Accurate dose delivery was validated using film and thermoluminescent dosimeter measurements with a solid water phantom. Gamma Knife plans were developed to irradiate intracranial and extracranial targets. Mice were irradiated validating successful targeted radiation dose delivery. Intramouse positional variability of the right mandible reference point across 10 micro-computed tomography scans was 0.65 ± 0.48 mm. Intermouse positional reproducibility across 2 mice at the same reference point was 0.76 ± 0.46 mm. The accuracy of dose delivery was 0.67 ± 0.29 mm and 1.01 ± 0.43 mm in the coronal and sagittal planes, respectively. The planned dose delivered to a mouse phantom was 2 Gy at the 50% isodose with a measured thermoluminescent dosimeter dose of 2.9 ± 0.3 Gy. The phosphorylated form of member X of histone family H2A (γH2AX) staining of irradiated mouse brain and mouse aorta demonstrated adjacent tissue sparing. In conclusion, our system for preclinical studies of small animal irradiation using the Gamma Knife is able to accurately deliver intracranial and extracranial targeted focal radiation allowing for preclinical experiments studying focal radiation.
authors.affiliation: 1 Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Musaddiq J
authors.initials: MJ
authors.lastname: Awan
authors.affiliation: 1 Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Dorth
authors.affiliation: 2 Department of Computer Science and Electrical Engineering, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Arvind
authors.initials: A
authors.lastname: Mani
authors.affiliation: 1 Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Haksoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: 1 Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: 1 Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Mazen
authors.initials: M
authors.lastname: Mislmani
authors.affiliation: 1 Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Welford
authors.affiliation: 1 Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Jiankui
authors.initials: J
authors.lastname: Yuan
authors.affiliation: 1 Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Barry W
authors.initials: BW
authors.lastname: Wessels
authors.affiliation: 1 Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Simon S
authors.initials: SS
authors.lastname: Lo
authors.affiliation: 3 Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: John
authors.initials: J
authors.lastname: Letterio
authors.affiliation: 1 Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Machtay
authors.affiliation: 4 Department of Neurosurgery, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Sloan
authors.affiliation: 1 Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Sohn
mesh_terms: D000818:Animals; D016371:Cranial Irradiation / Q000379:methods*; D004195:Disease Models, Animal; D005720:Gamma Rays; D019416:Head Movements; D006801:Humans; D051379:Mice; D056888:Patient Positioning; D011874:Radiometry; D016634:Radiosurgery / Q000379:methods; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D020266:Radiotherapy, Conformal / Q000379:methods; D015203:Reproducibility of Results
keywords: conformal radiotherapy; preclinical models; radiation biology; radiation physics; small animal irradiation