Advanced Real-time MR-Guided Radiofrequency Ablation of Cardiac Arrhythmias

在英国，每年有200万人患有心律失常。射频消融(RFA)是临床上治疗大多数心律失常的有效方法。总体而言，英国每年进行约20,000例心律失常的RFA治疗。RFA使用基于导管的局部射频能量传递，从而导致局部组织加热。足够的温度升高(约30-50摄氏度，持续约30-60秒)是造成永久性组织破坏(坏死)的必要条件。RFA手术的目的是对导致心律失常的关键心脏组织造成永久性组织破坏。这通常是通过创建永久性消融损伤线来电阻塞/隔离这些关键部位来实现的。由于每个消融点的最大尺寸为~6-8 mm，因此通常进行多次消融以产生消融线。目前，30-50%的RFA手术失败是由于消融线上存在间隙，以及永久性RFA病变的位置/范围不正确。此外，RFA手术可能有严重的并发症，包括心脏穿孔，当组织温度超过100摄氏度时，可能会因蒸汽爆炸而引起心脏穿孔。最后，在RFA过程中应防止潜在的导管漂移，以避免消融不需要的组织。目前的实时RFA引导系统(X射线、电解剖标测)无法监测组织温度和永久性RFA病变的范围。间接参数如射频功率/持续时间、导管尖端温度、导管接触力/阻抗在RFA过程中被监测，但对组织温度和永久性RFA病变范围的预测值较低。值得注意的是，导管尖端温度和组织温度之间的差异可以是&gt；30℃。因此，实时准确地监测组织温度和预测永久性RFA病变范围非常有可能改善手术的结果和安全性。磁共振(MR)温度测量是一种非侵入性MRI技术，可以实时地以像素为单位评估组织深处的温度。永久性组织破坏可以使用基于温度升高和暴露时间模型的热剂量(此后称为MR剂量学)的概念来预测。然而，目前的心脏MR测温/剂量学方法(采集窗口长、空间分辨率低、对生理运动的敏感性和温度图中的高噪声水平)和临床可行的方法仍有待验证，其在防止消融间隙和预测慢性永久性RFA病变范围方面的准确性仍有待验证。这项研究计划旨在开发一种新的临床上可行的实时心脏MR测温/剂量学框架，以满足当前尚未满足的需求，在临床前研究中评估其性能，并在首例临床研究中证明其可行性。

Cardiac arrhythmias affect 2 million people a year in the UK. Radio-frequency (RF) ablation (RFA) procedures are clinically available to treat the majority of cardiac arrhythmias. Overall, ~20,000 RFA of cardiac arrhythmias are being performed every year in the UK. RFA uses catheter-based localized delivery of radio-frequency energy resulting in localized tissue heating. Sufficient temperature increase (~30-50C for ~30-60sec) is necessary to create permanent tissue destruction (necrosis). The aim of RFA procedures is to create permanent tissue destruction of critical heart tissues causing arrhythmias. This is often achieved by creating lines of permanent ablation lesions to electrically block/isolate these critical sites. Since each ablation point has a maximum size of ~6-8mm, multiple ablations are commonly performed to create ablation lines. Currently, 30-50% of RFA procedures fail due to the presence of gaps in ablation lines and the incorrect location/extent of the permanent RFA lesions. Furthermore, RFA procedures may have severe complications including cardiac perforation which can arise from steam explosion occurring when tissue temperature exceeds 100C. Finally, potential catheter drift during RFA should be prevented to avoid ablation of undesired tissues. Current real time RFA guidance systems (X-ray, electro-anatomical mapping) are unable to monitor tissue temperature and extent of permanent RFA lesions. Indirect parameters such as RF power/duration, catheter tip temperature, catheter contact force/impedance are monitored during RFA but have low predictive values of tissue temperature and permanent RFA lesion extent. Notably, the discrepancy between the catheter-tip temperature and tissue temperature can be >30C. Therefore, real time accurate monitoring of tissue temperature and prediction of permanent RFA lesion extent is very likely to improve the outcome and safety of the procedure.Magnetic resonance (MR)-thermometry is a non-invasive MRI technique which enables real time pixel-wise assessment of temperature, deep in tissue. Permanent tissue destruction can be predicted using the concept of thermal dose (thereafter referred to as MR-dosimetry) which is based on a model of temperature elevation and time of exposure. However, current cardiac MR-thermometry/dosimetry methods that are not ideal for clinical translation (long acquisition window, low spatial resolution, sensitivity to physiological motion, and high noise level in temperature maps) and a clinically feasible method remains still to be demonstrated, as does its accuracy for prevention of ablation gaps and prediction of chronic permanent RFA lesion extent. This research proposal aims to develop a novel clinically feasible real-time cardiac MR-thermometry/dosimetry framework which addresses the current unmet need, to evaluate its performance in a pre-clinical study, and to demonstrate its feasibility in a first-in-man clinical study.