Pathological Assessment of Cardiac Radioablation to the Cavotricuspid Isthmus without Gating and Real-Time Tracking in Mini Pigs

Abstract

<h3>Purpose/Objective(s)</h3> 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. Although we used the motion management by compression techniques for the reduction of the internal target volume, we did not use the gating and real-time tracking techniques. We assessed the necessity of the precise target planning and monitoring the complex respiratory and cardiac motion to cardiac radioablation to the cavotricuspid isthmus (CTI) by pathological assessment in mini pigs. <h3>Materials/Methods</h3> All animal procedures were approved by institutional animal care and use committee and performed in full compliance with its guidelines. Four mini pigs underwent magnetic resonance (MR) and electrophysiology assessment using electroanatomic mapping (EAM) before and 3 months after SBRT with single-fraction doses of 25Gy. The target of CTI was defined by cardiologist. We defined the internal margin (IM), respiratory: SI 7 mm, AP 3 mm, LR 3 mm, cardiac motion: 3 mm in all direction and set up margin (SM): 5 mm in all direction. Then, planning target volume (PTV) margin: IM + SM = SI 15 mm, AP 10mm, LR 10 mm were added to the target, defining PTV.MR examination, including diffusion-weighted, dynamic Gd-enhanced, spectroscopy, and T2-weighted images were performed before and 3 months after SBRT, followed by histopathologic examination. Radiation oncologist and radiologist evaluated the detectability and image quality for the irradiated site. MRI findings of the CTI radioablation lesion was compared to electrophysiology and histopathology findings. <h3>Results</h3> 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. MRI could not detect the radiation injury clearly. Pathological examinations were analyzed after 3 months of follow-up, fibrous hyperplasia and capillary hyperplasia were observed around the nerve bundle beyond CTI in all pigs. The atrophy and necrosis of the nerve bundle itself is scarce. <h3>Conclusion</h3> These data demonstrated the feasibility of SBRT for creating conduction block across the CTI in mini pigs. Fibrosis or scarring around the nerve bundle beyond CTI may affect the radiation injury. Then, precise margins of cardiac radioablation to the cavotricuspid isthmus will reduce the radiation injury. Not only gating and breath-hold, but also including the use of real-time tracking such as MRI-guidance cardiac radiosurgery will open the possibility of treating cardiac arrhythmias patients completely safety and noninvasively.