High-energy ion beams are successfully used in cancer therapy and precisely deliver high doses of ionizing radiation to small deep-seated target volumes. A similar noninvasive treatment modality for cardiac arrhythmias was tested here. This study used high-energy carbon ions for ablation of cardiac tissue in pigs. Doses of 25, 40, and 55 Gy were applied in forced-breath-hold to the atrioventricular junction, left atrial pulmonary vein junction, and freewall left ventricle of intact animals. Procedural success was tracked by (1.) in-beam positron-emission tomography (PET) imaging; (2.) intracardiac voltage mapping with visible lesion on ultrasound; (3.) lesion outcomes in pathohistolgy. High doses (40–55 Gy) caused slowing and interruption of cardiac impulse propagation. Target fibrosis was the main mediator of the ablation effect. In irradiated tissue, apoptosis was present after 3, but not 6 months. Our study shows feasibility to use high-energy ion beams for creation of cardiac lesions that chronically interrupt cardiac conduction.

Treatment planning of 12C with delivery of physical ionizing radiation doses that have been described to induce complete block is feasible for AF ablation, considering human anatomy, dose constraints, and encasing underlying motion patterns from respiration and cardiac contraction at the LA-PV junction into treatment planning.

Accurate dose delivery to extra-cranial lesions requires tumor motion compensation. An effective compensation can be achieved by real-time tracking of the target position, either measured in fluoroscopy or estimated through correlation models as a function of external surrogate motion. In this work, we integrated two internal/external correlation models (a state space model and an artificial neural network-based model) into a custom infra-red optical tracking system (OTS). Dedicated experiments were designed and conducted at GSI (Helmholtzzentrum für Schwerionenforschung). A robotic breathing phantom was used to reproduce regular and irregular internal target motion as well as external thorax motion. The position of a set of markers placed on the phantom thorax was measured with the OTS and used by the correlation models to infer the internal target position in real-time. Finally, the estimated target position was provided as input for the dynamic steering of a carbon ion beam. Geometric results showed that the correlation models transversal (2D) targeting error was always lower than 1.3 mm (root mean square). A significant decrease of the dosimetric error with respect to the uncompensated irradiation was achieved in four out of six experiments, demonstrating that phase shifts are the most critical irregularity for external/internal correlation models.

Background— Particle therapy, with heavy ions such as carbon-12 ( 12 C), delivered to arrhythmogenic locations of the heart could be a promising new means for catheter-free ablation. As a first investigation, we tested the feasibility of in vivo atrioventricular node ablation, in Langendorff-perfused porcine hearts, using a scanned 12C beam. Methods and Results— Intact hearts were explanted from 4 (30–40 kg) pigs and were perfused in a Langendorff organ bath. Computed tomgraphic scans (1 mm voxel and slice spacing) were acquired and 12 C ion beam treatment planning (optimal accelerator energies, beam positions, and particle numbers) for atrioventricular node ablation was conducted. Orthogonal x-rays with matching of 4 implanted clips were used for positioning. Ten Gray treatment plans were repeatedly administered, using pencil beam scanning. After delivery, positron emission tomography-computed tomgraphic scans for detection of β + ( 11 C) activity were obtained. A 12 C beam with a full width at half maximum of 10 mm was delivered to the atrioventricular node. Delivery of 130 Gy caused disturbance of atrioventricular conduction with transition into complete heart block after 160 Gy. Positron emission computed tomgraphy demonstrated dose delivery into the intended area. Application did not induce arrhythmias. Macroscopic inspection did not reveal damage to myocardium. Immunostaining revealed strong γH2AX signals in the target region, whereas no γH2AX signals were detected in the unirradiated control heart. Conclusions— This is the first report of the application of a 12 C beam for ablation of cardiac tissue to treat arrhythmias. Catheter-free ablation using 12C beams is feasible and merits exploration in intact animal studies as an energy source for arrhythmia elimination.