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

Publication ,  Journal Article
Yoon, SW; Cramer, CK; Miles, DA; Reinsvold, MH; Joo, KM; Kirsch, DG; Oldham, M
Published in: Med Phys
November 2017

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 < 1). Agreement is less at 1 mm and ±5% at 69.0% gamma passing rate. The four-field plan was further validated with immunohistochemistry and showed a significant reduction in DNA double-strand breaks within the spared region compared with whole-brain irradiated groups (P = 0.021). However, coverage of the whole brain was low at 48.5-57.8% of the volume receiving 30Gy at 7Gy mean hippocampal dose in simulation and 46.7-52.5% in dosimetric measurements. This can be attributed to the shape of the rat hippocampus and the inability of treatment platform to employ non-coplanar beams. CONCLUSION: A novel approach for conformal microradiation therapy using 3D-printing technology was developed, implemented, and validated. A workflow was developed to generate accurate 3D-printed blocks from registered high-resolution rat MRI atlas structures. Although hippocampus was spared with this technique, whole-brain target coverage was suboptimal, indicating that non-coplanar beams and IMRT capability may be required to meet stringent dose criteria associated with current human RTOG trials.

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Published In

Med Phys

DOI

EISSN

2473-4209

Publication Date

November 2017

Volume

44

Issue

11

Start / End Page

6008 / 6017

Location

United States

Related Subject Headings

  • Rats, Wistar
  • Rats
  • Radiotherapy, Conformal
  • Radiotherapy Planning, Computer-Assisted
  • Radiometry
  • Printing, Three-Dimensional
  • Organs at Risk
  • Nuclear Medicine & Medical Imaging
  • Hippocampus
  • Brain Neoplasms
 

Citation

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Chicago
ICMJE
MLA
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Yoon, S. W., Cramer, C. K., Miles, D. A., Reinsvold, M. H., Joo, K. M., Kirsch, D. G., & Oldham, M. (2017). A precision 3D conformal treatment technique in rats: Application to whole-brain radiotherapy with hippocampal avoidance. Med Phys, 44(11), 6008–6017. https://doi.org/10.1002/mp.12533
Yoon, Suk W., Christina K. Cramer, Devin A. Miles, Michael H. Reinsvold, Kyeung M. Joo, David G. Kirsch, and Mark Oldham. “A precision 3D conformal treatment technique in rats: Application to whole-brain radiotherapy with hippocampal avoidance.Med Phys 44, no. 11 (November 2017): 6008–17. https://doi.org/10.1002/mp.12533.
Yoon SW, Cramer CK, Miles DA, Reinsvold MH, Joo KM, Kirsch DG, et al. A precision 3D conformal treatment technique in rats: Application to whole-brain radiotherapy with hippocampal avoidance. Med Phys. 2017 Nov;44(11):6008–17.
Yoon, Suk W., et al. “A precision 3D conformal treatment technique in rats: Application to whole-brain radiotherapy with hippocampal avoidance.Med Phys, vol. 44, no. 11, Nov. 2017, pp. 6008–17. Pubmed, doi:10.1002/mp.12533.
Yoon SW, Cramer CK, Miles DA, Reinsvold MH, Joo KM, Kirsch DG, Oldham M. A precision 3D conformal treatment technique in rats: Application to whole-brain radiotherapy with hippocampal avoidance. Med Phys. 2017 Nov;44(11):6008–6017.

Published In

Med Phys

DOI

EISSN

2473-4209

Publication Date

November 2017

Volume

44

Issue

11

Start / End Page

6008 / 6017

Location

United States

Related Subject Headings

  • Rats, Wistar
  • Rats
  • Radiotherapy, Conformal
  • Radiotherapy Planning, Computer-Assisted
  • Radiometry
  • Printing, Three-Dimensional
  • Organs at Risk
  • Nuclear Medicine & Medical Imaging
  • Hippocampus
  • Brain Neoplasms