T. Mori1, F. Hyodo2, T. Mori3, N. Koyasu4, A. Kobori1, H. Takano5, C. Makita5, and M. Matsuo5; 1Department of Radiology, Graduate School of Medicine, Gifu University, Gifu, Japan, 2Department of Pharmacology, Graduate School of Medicine, Gifu University, Gifu, Japan, 3Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan, 4NIH/NCI, Bethesda, MD, 5Gifu University School of Medicine, Department of Radiology, Gifu, Japan
Purpose/Objective(s): Since the introduction of intensity-modulated radiation therapy (IMRT), new technologies have continued developing to achieve higher treatment efficacy and the lower side effects as possible. Recently, MR-Linac has also been introduced to clinical practice, enabling more precise image-guided radiation therapy (IGRT). However, no method has been developed to visualize the actual dose and site after X-ray irradiation. Imaging free radicals generated by irradiation will lead to better understanding of the treatment dose and site. We have been developing the free radical imaging methods using Dynamic Nuclear Polarization (DNP)-MRI with nitroxyl radicals as a redox probe (e.g. 4-Methacryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempo methacrylate; TempoMC)). We previously demonstrated that the mixed solution of TempoMC and glutathione (GSH) was useful as a probe for quantitative detection of free radical reactions, allowing us to observe the redox reaction after irradiation clearly. In this study, we investigated the possibility of in vivo spatiotemporal visual verification of our X-ray visualization system based on redox reaction by in vivo DNP-MRI. Materials/
Methods: We prepared balloon phantoms filled with 0.5 mL TempoMC/GSH solution which were made of a urinary catheter balloon and implanted in the abdominal cavity of mice. IMRT plan was prepared by the software used in daily clinical practice, and then each mouse was irradiated X-ray with 2.5Gy, 5.0Gy, and 10Gy by helical Tomotherapy. Free radical imaging by low filed type of DNP-MRI, ESR signal measurements, and MRI imaging were performed on the mice after irradiation. Results: Balloon phantoms in the abdominal cavity of mice were well delineated on T1-weighted and T2-weighted MRI and clearly visualized by DNP-MRI. The DNP-MRI signal of TempoMC/GSH phantoms were decreased depending on prescribed irradiation dose. In addition, a linear relationship between the DNP-MRI signals and the irradiation dose was observed. EPR signal of remaining TempoMC radical in the balloon phantoms were decreased by irradiation and well corresponded to that of in vivo imaging data. Conclusion: DNP-MRI enables visual verification of IMRT in vivo. Quantitative visualization of irradiated dose from signal values is expected with the accumulation of data. Therefore, this study has potential for application to new systems such as MR-Linac for more precise radiotherapy.