A precision 3D conformal treatment technique in rats: Application to whole‐brain radiotherapy with hippocampal avoidance

• Published in: Medical physics (Lancaster) 2017-11, Vol.44 (11), p.6008-6017
• Main Authors: Yoon, Suk W., Cramer, Christina K., Miles, Devin A., Reinsvold, Michael H., Joo, Kyeung M., Kirsch, David G., Oldham, Mark
• Format: Article
• Language: English
• Subjects: 3D printer; Animals; Brain Neoplasms - radiotherapy; hippocampal avoidance; Hippocampus - radiation effects; Organs at Risk - radiation effects; preclinical study; Printing, Three-Dimensional; Radiometry; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Conformal - adverse effects; Radiotherapy, Conformal - methods; Rats; Rats, Wistar; RTOG 0933; small animal irradiator
• ISSN: 0094-2405; 2473-4209
• DOI: 10.1002/mp.12533

Purpose To develop and validate three‐dimensional (3D) conformal hippocampal sparing whole‐brain radiation therapy (HA‐WBRT) for Wistar rats utilizing precision 3D‐printed immobilization and micro‐blocks. This technique paves the way for future preclinical studies investigating brain treatments that reduce neurotoxicity. Methods and materials A novel preclinical treatment planning and delivery process was developed to enable precision 3D conformal treatment and hippocampal avoidance capability for the Xrad 225cx small animal irradiator. A range of conformal avoidance plans were evaluated consisting of equiangularly spaced coplanar axial beams, with plans containing 2, 4, 7, and 8 fields. The hippocampal sparing and coverage of these plans were investigated through Monte Carlo dose calculation (SmART‐Plan Xrad 225cx planning system). Treatment delivery was implemented through a novel process where hippocampal block shapes were computer generated from an MRI rat atlas which was registered to on‐board cone beam CT of the rat in treatment position. The blocks were 3D printed with a tungsten‐doped filament at lateral resolution of 80 μm. Precision immobilization was achieved utilizing a 3D‐printed support system which enabled angled positioning of the rat head in supine position and bite block to improve coverage of the central diencephalon. Treatment delivery was verified on rodent‐morphic Presage® 3D dosimeters optically scanned at 0.2‐mm isotropic resolution. Biological verification of hippocampal avoidance was performed with immunohistologic staining. Results All simulated plans spared the hippocampus while delivering high dose to the brain (22.5–26.2 Gy mean dose to brain at mean hippocampal dose of 7 Gy). No significant improvement in hippocampal sparing was observed by adding beams beyond four fields. Dosimetric sparing of hippocampal region of the four‐field plan was verified with the Presage® dosimeter (mean dose = 9.6 Gy, D100% = 7.1 Gy). Simulation and dosimeter match at distance‐to‐agreement of 2 mm and dose difference of ±3% at 91.7% gamma passing rate (passing criteria of γ