MRI-guided 3D conformal arc micro-irradiation of a F98 glioblastoma rat model using the Small Animal Radiation Research Platform (SARRP)

Abstract

Current glioblastoma (GB) small animal models for cranial radiation therapy (RT) use simple single beam technologies, which differ from the advanced conformal image-guided radiation techniques used in clinical practice. This technological disparity presents a major disadvantage for the development of new therapeutic approaches. Hence, we established a F98 GB rat model using magnetic resonance imaging (MRI)-guided three-dimensional (3D)-conformal arc RT with the Small Animal Radiation Research Platform (SARRP). Ten Fischer rats were inoculated with F98 tumor cells. When the tumor reached a volume of approximately 27 mm(3) on T2-weighted MR images, the animals were randomized into a treatment group (n = 5) receiving RT and concomitant temozolomide, and a sham group (n = 5) receiving control injections. For the treated animals, contrast-enhanced T1-weighted MR images were acquired followed by a cone-beam computed tomography (CBCT) on the SARRP system. Both scans were co-registered; MRI was used to define the target whereas CBCT was used for calculating a dose plan (20 Gy, three non-coplanar arc beams, 3 × 3 mm collimator). Tumor volumes were evaluated on follow-up contrast-enhanced T1-weighted MR images. Verification of treatment accuracy with γH2AX immunohistochemical staining was performed. Tumors in the control animals showed rapid proliferation during follow-up, encompassing almost the entire right cerebral hemisphere at day 12-15. Treated animals showed no significant tumor growth from 2 to 9 days post RT. γH2AX results confirmed the accuracy of dose delivery. This model, which is quite similar to the approach in the clinic, is valid for combined RT and chemotherapy of GB in rats.

Kinetic Modeling and Graphical Analysis of 18F-Fluoromethylcholine (FCho), 18F-Fluoroethyltyrosine (FET) and 18F-Fluorodeoxyglucose (FDG) PET for the Fiscrimination between High-Grade Glioma and Radiation Necrosis in Rats

“…On the day of PET imaging, the mean contrast enhancing tumor volume on T1-weighted MRI was 99 ± 73 mm 3 (n = 16). GB histology was confirmed (Fig 1D) [9,23]. …”

“…Conformal arc micro-irradiation was optimized previously [23]. 3 arcs and a 3x3 mm collimator were used for the delivery of 60 Gy in a single dose (Fig 1E).…”

An efficient and robust MRI-guided radiotherapy planning approach for targeting abdominal organs and tumours in the mouse

“…Although physical separation of the abdominal structures was achieved, the accuracy of dose estimation remained limited [6]. Other imaging modalities such as Positron Emission Tomography (PET) and Bioluminescence imaging (BLI) also have been proposed to guide targeting and delivery of radiotherapy [2, 9–11] but both techniques have their inherent limitations. BLI is restricted by its light penetration depth, lack of true tomography imaging and requires the use of reporter genes whilst PET applications are also limited by partial volume effects and in some cases, inadequate contrast specificity.…”

“…However, MRI has to date been used merely as a descriptor of target location [2, 12] in studies involving organs other than the brain. MRI-guided radiotherapy (RT) has only focussed on brain, an organ that is easy to immobilise with internal, fixed landmarks [2, 9, 11, 12]. As such, the skull’s bright intensity on CT but dark intensity on MRI was used to drive a rigid body registration.…”

Quality Assessment of Stereotactic Radiosurgery of a Melanoma Brain Metastases Model Using a Mouselike Phantom and the Small Animal Radiation Research Platform

“…Advanced beam delivery including non-coplanar treatment fields and arc therapy. [6] Prior studies have demonstrated the efficacy of radiation administered using the SARRP to intracranial tumors. [5,7,8] However, the question remains whether the treatment is precise and the dose is accurate.…”