Novel imaging and treatment technologies for image-guided noninvasive stereotactic cardiac radiosurgery

摘要 由室性心动过速（VT）引起的心源性猝死（SCD）导致> 150，000例死亡/年 在美国，无创立体定向心脏放射外科（NSCR）最近被报道为一种新的， 治疗标准药物和导管消融难治性室性心动过速的替代无创治疗选择 治疗（Cuculich和罗宾逊，NEJM，2017年12月）。5名患者的初步结果显示， 6周后VT发作减少，导致2016-2018年I/II期临床试验 （ClinicalTrials.gov NCT 02919618）。I/II期试验的初步结果显示了相似的疗效 （出版物待定）与初步试点研究相结合。目前，目标体积比 致瘤组织，以确保在存在以下物质的情况下将治疗剂量递送至心脏病变 心脏和呼吸运动。尽管有证据支持疗效，但必须尽量减少 大量健康心脏组织不必要地接受高辐射剂量治疗，以降低 晚期并发症（包括心包炎、心绞痛、心肌梗死和加速动脉粥样硬化）。 本研究的临床目标是：1）提高放射束指向 患病的心肌组织; 2）减少对心脏周围健康组织的辐射毒性， 肺和食管;和3）提高整体NSCR治疗效果。这些目标将是 使用新的放射治疗过程、目标定义、成像、图像引导 目标运动跟踪和预测，以及辐射传递门控方法。新的MRI和锥形束 将开发CT（CBCT）图像采集和重建方法， 补偿心脏和呼吸运动，并显著改善目标清晰度和运动 NSCR的管理组件。新的NSCR处理工艺将被开发，以减少 治疗当天的患者摆位不确定性，并通过 跟踪所述目标运动并基于所述实时目标位置和所述目标运动来选通所述辐射束。 呼吸+ ECG信号。新的治疗和成像方法开发和测试下， 研究将适用于MRI引导辐射输送系统（MR-Linacs）和CBCT成像 引导辐射输送系统（CBCT-直线加速器）。

Abstract Sudden cardiac death (SCD) caused by ventricular tachycardia (VT) results in >150,000 deaths/year in the U.S. Noninvasive Stereotactic Cardiac Radiosurgery (NSCR) was recently reported as a novel and alternative noninvasive treatment option to treat VT refractory to standard drug and catheter ablation therapy (Cuculich and Robinson, NEJM, Dec. 2017). The initial results for five patients resulted in a 99.9% reduction of VT episodes after 6 weeks, leading to a Phase I/II clinical trial in 2016-2018 (ClinicalTrials.gov NCT02919618). The preliminary results of Phase I/II trial showed similar efficacy (publication is pending) to the initial pilot study. Currently, the target volume is ~3 times larger than the arrhythmogenic tissue to ensure the therapeutic dose is delivered to the cardiac lesion in the presence of cardiac and respiratory motion. Despite evidence supporting efficacy, it is essential to minimize the volume of healthy cardiac tissue unnecessarily treated to high radiation doses to reduce the likelihood of late complications (including pericarditis, angina, myocardial infarction and accelerated atherosclerosis). Our clinical goals of this study are to: 1) Improve the accuracy of directing the radiation beam to the diseased myocardial tissue; 2) Reduce radiation toxicity to the surrounding healthy tissues of the heart, lungs and esophagus; and 3) Improve the overall NSCR treatment efficacy. These goals will be accomplished using novel radiation treatment processes, target definition, imaging, image guidance, target motion tracking and prediction, and radiation delivery gating methods. New MRI and cone beam CT (CBCT) image acquisition and reconstruction methods will be developed to characterize and compensate for cardiac and respiratory motion, and to dramatically improve target definition and motion management components of NSCR. New NSCR treatment processes will be developed to reduce the patient setup uncertainties on the treatment day, and to improve the radiation delivery accuracy by tracking the target motion and gating the radiation beam based on the real-time target position and the respiratory + ECG signals. The new treatment and imaging methods developed and tested under this study will be applicable to both MRI-guided radiation delivery systems (MR-Linacs) and CBCT image guided radiation delivery systems (CBCT-Linacs).