3398 - A Large Animal Study of a Novel Cardiac-Ultrasound Image Guidance for Cardio-Respiratory-Gated Radiation Ablation to Ventricular Tachycardia Targets Using Proton Therapy
Presenter(s)
Y. L. E. E. Chen1, F. J. Bijari1, H. P. Deng1, N. Depauw1, A. Garonna2, J. Kang1, H. Kim1, M. Soccorso1, S. H. Moon1, M. Normandin3, R. Woodcock1, K. M. Yaghoubian1, R. A. Levine1, H. I. Lehmann4, G. El Fakhri5, K. W. Jee1, and Y. Chemli3; 1Massachusetts General Hospital, Boston, MA, 2EBAMed SA, Geneva, Switzerland, 3Yale University, New Haven, CT, 4University of Utah, Salt Lake City, UT, 5Yale, New Haven, CT
Purpose/Objective(s): Radiation ablation is an emerging non-invasive option for treating ventricular tachycardia. However, challenges such as scatter dose to OARs, cardiac and respiratory motion and the need for functional imaging biomarkers persist. This large animal study aimed to evaluate the safety and feasibility of cardiac and respiratory gated protons using a novel ultrasound-based image guidance system (CardioKit) and PET-based membrane potential imaging as a novel biomarker for early radiation-induced myocardial effects.
Materials/Methods: On an IACUC approved protocol, six healthy swine underwent 4D cardiac and/or respiratory CTs. An expert radiation oncologist defined a 3 cm transmural GTV in the free wall of the left ventricle simulating a VT focus, expanded to an ITV of all cardiac phases for single-gating or 70-100% R-R window (mid-diastole) for dual gating, and added 5 mm for PTV. The PTV was prescribed to 35 GyRBE (RBE=1.1) in a single fraction using 100-150 MeV protons. Aperture edge allowed sharp dose drop-off and Dmax 15 GyRBE for L coronary art. CardioKit allowed for real-time (50fps) cardiac positioning and a new proton scanning control delivered the dose with minimal latency (<550 µs). Layer repainting mitigated cardiac and respiratory motion.
Safety, tolerability, imaging, and outcomes of the ablation were assessed using blood work, close veterinary observation, echocardiography, contrast CT and dynamic PET, and eventual necropsy at week 14. Specifically, membrane potential Imaging with a lipophilic cationic PET tracere [18F]FTPP+ PET was investigated as a novel biomarker for early radiation effects on cardiac tissue by mapping membrane potential (??T) before and after irradiation. Data were analyzed using kinetic modeling and compared with histological findings. Animals were euthanized at 14 weeks and necropsy and a pathologist assessed the ablated LV lesions as well as nearby OARs.Results: ITV expansion from GTV was larger for single gating than for dual gating (64% vs 19%). All animals remained healthy throughout the 14-week follow-up with no detectable changes in cardiac function (LVEF). Dynamic PET imaging showed significant ??T depolarization in irradiated myocardial segments (mean differences of 8.5 mV at 8 weeks, 31.3 mV at 14 weeks). Although statistical significance was limited due to sample size, the trend suggests early functional changes before fibrosis. Necropsy confirmed successful induction of hemorrhagic and necrotic transmural lesions and no significant other toxicity in the surrounding tissue.
Conclusion: This pilot shows the feasibility and safety of proton therapy for VT ablation to a smaller more precise target using dual cardiac-respiratory gating and a novel echocardiography based IGRT (CardioKit). [18F]FTPP+ PET emerges as a potential imaging biomarker for early effects of protons on myocardial membrane potential, warranting further investigation in larger studies as a foundation for potential human trials.
Funding: Supported by EBAMed SA.