Oliver Blanck1, Frank Bode2, Maximilian Gebhard3, Peter Hunold4, Sebastian Brandt5, Ralf Bruder6, Martin Grossherr5, Reinhard Vonthein7, Dirk Rades8, Juergen Dunst9. 1. Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany; CyberKnife Center Northern Germany, Guestrow, Germany. Electronic address: oliver.blanck@uksh.de. 2. Medical Department II, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany. 3. Institute of Pathology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany. 4. Department of Radiology and Nuclear Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany. 5. Department of Anaesthesiology and Intensive Care Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany. 6. Institute for Robotics and Cognitive Systems, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany. 7. Institute of Medical Biometry and Statistics, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany. 8. Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany. 9. Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany; University Copenhagen, Denmark.
Abstract
PURPOSE: To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. METHODS AND MATERIALS: Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm(3)). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. RESULTS: Transmural scarring of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. CONCLUSIONS: Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.
PURPOSE: To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. METHODS AND MATERIALS: Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm(3)). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. RESULTS: Transmural scarring of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. CONCLUSIONS: Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.
Authors: Ping Xia; Rupesh Kotecha; Naveen Sharma; Martin Andrews; Kevin L Stephans; Carlos Oberti; Sara Lin; Oussama Wazni; Patrick Tchou; Walid I Saliba; John Suh Journal: Cureus Date: 2016-07-11
Authors: David Krug; Oliver Blanck; Thomas Demming; Matthias Dottermusch; Karoline Koch; Markus Hirt; Laura Kotzott; Adrian Zaman; Lina Eidinger; Frank-Andre Siebert; Jürgen Dunst; Hendrik Bonnemeier Journal: Strahlenther Onkol Date: 2019-10-31 Impact factor: 3.621
Authors: Oliver Blanck; Svenja Ipsen; Mark K Chan; Ralf Bauer; Matthias Kerl; Peter Hunold; Volkmar Jacobi; Ralf Bruder; Achim Schweikard; Dirk Rades; Thomas J Vogl; Peter Kleine; Frank Bode; Jürgen Dunst Journal: Cureus Date: 2016-07-20
Authors: Houda Bahig; Jacques de Guise; Toni Vu; Carl Chartrand-Lefebvre; Danis Blais; Martin Lebeau; Nhu-Tram Nguyen; David Roberge Journal: Cureus Date: 2016-07-26