Abstract

Cardiac arrhythmias are usually treated with invasive, time consuming catheter ablation techniques. While recently stereotactic body radiotherapy (SBRT) is an emerging non-invasive treatment in the management of cardiac arrhythmias. To identify and assess the cardiac radioablation by MR examination, including diffusion-weighted MRI, dynamic Gd-enhanced MRI, MR spectroscopy, and T2-weighted MRI early after SBRT is very difficult. 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)). In this study, we examined the possibility of in vivo spatiotemporal visualization of SBRT for cardiac radioablation to the cavotricuspid isthmus (CTI) based on redox reaction by in vivo DNP-MRI. All animal procedures were approved by institutional animal care and use committee and performed in full compliance with its guidelines. This study was conducted with two approaches. First, four mini pigs underwent electrophysiology assessment using electroanatomic mapping (EAM) before and 3 months after SBRT with single-fraction doses of 25 Gy. The target of CTI was defined by cardiologist. We defined the planning target volume (PTV): the internal margin (IM) + set up margin (SM) = SI 15 mm, AP 10mm, LR 10 mm were added to the target. Radiotherapy plans were created by the software used in daily clinical practice. Second, free radical imaging by low filed type of DNP-MRI was performed on the four mice before and after 25 Gy and 10 Gy irradiation to whole heart. ESR signal measurements were also performed. A total dose of 25 Gy was successfully delivered to PTV in a single procedure in all mini pigs. EAM visualized the irradiated site and confirmed clockwise conduction block across the CTI. Although routine MRI could not detect the cardiac radiation injury clearly, the four mice of heart were well delineated on MRI and clearly visualized by DNP-MRI. DNP-MRI signal of TempoMC were decreased depending on prescribed irradiation dose. These data demonstrated the safety and feasibility of SBRT for creating conduction block across the CTI in mini pigs. Although to identify and assess the irradiated site by routine MR examination was impossible, the free radical imaging methods using Dynamic Nuclear Polarization (DNP)-MRI with TempoMC could be a promising successful method for the assessment of cardiac radioablation. This new quantum image by DNP-MRI will open the possibility of treating cardiac arrhythmias by SBRT safety and noninvasively.

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