Highly Conformal Radiation Planning of Orthotopic Glioblastoma Model In Mice Using 9.4T MRI Scans to Simulate Human Treatment
Abstract
Purpose
Preclinical glioblastoma (GBM) models are crucial for the development of novel therapeutic strategies to improve GBM outcomes. Highly conformal conventional fractionation forms the basis for standard-of-care radiotherapy (RT) in human GBM. However, most preclinical RT utilize whole-brain fields and hypofractionation limiting translational potential. Therefore, this study was designed to improve preclinical translation through a novel procedure for highly conformal RT planning in an orthotopic GBM murine model using MR imaging at 9.4T.
Methods
Ten 7-week-old C57BL/6J mice (4 female, 6 male) were implanted with approximately 20,000 SB28 GBM cells into the right hemisphere stereotactically. Tumor growth was monitored through bioluminescent imaging. Multislice fast-spin-echo MRI in axial and sagittal orientations were obtained for the mice using the 9.4T MR scanner 9 days post implantation. The MRIs were registered to micro-CBCT images acquired with the Xstrahl Small Animal Radiation Research Platform (SARRP) to better delineate tumor and OAR volumes. Conformal RT plans utilizing both dynamic and static beam arrangements were generated for 6 mice using the MuriPlan TPS. These mice were prescribed 40.05 Gy in 15 fractions to the tumor volume.
Results
Fused MR-CBCT images allowed precise delineation of target volumes and OARs allowing generation of highly conformal dose distributions similar to human GBM RT planning. The minimum, maximum, and mean PTV doses for the 6 mice averaged 36.08, 47.09, and 43.16 Gy respectively. On average, the normal brain tissue received mean and maximum doses of 15.28 Gy and 44.39 Gy respectively, whereas the contralateral hemisphere received 10.29 Gy and 38.30 Gy respectively.
Conclusion
Combining 9.4T MRI with highly conformal planning techniques on the SARRP permits target coverage while reducing normal brain irradiation. Importantly, planning dose and plan quality indices are similar to those reported for GBM patients maximizing the translational potential of preclinical data to clinical applications.