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

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.

This research will deliver impact at multiple levels.

A) Impact on healthcare and the NHS
Cardiac arrhythmias affect 2 million people a year in the UK. Radio-frequency ablation (RFA) procedures are clinically available to treat a majority of cardiac arrhythmias such as atrial fibrillation or ventricular tachycardia (VT). Overall, ~20,000 RFA of cardiac arrhythmias are being performed every year in the UK. Currently, 30-50% of RFA procedures fail because of the presence of gaps in ablation lines and incorrect location/extent of permanent RFA lesions. Our initial clinical target will be CMR-guided VT ablation procedures. 28,000 individuals die annually of sudden cardiac death (SCD) as a consequence of VT in England and Wales. Implantable cardioverter defibrillator (ICD) therapy is a first line treatment for SCD prevention but is not curative. VT ablation is an additional treatment which reduces the morbidity/mortality in patients with ICD. Although VT ablation is a curative therapy, this procedure currently fails in 50% of cases, requires repeat procedures and is associated with complications (3% mortality). This research aim at developing a novel approach to VT ablation using real-time cardiac magnetic resonance imaging (CMR) guidance.
A method of VT ablation that has a much higher success rate would have substantial impact on healthcare and the NHS. First, it would reduce adverse events and poor quality of life related to appropriate and inappropriate ICD shocks. Second, it could also transform the current care pathway by simply alleviating the need of costly ICDs. An efficient method to VT ablation would also substantially reduce the need of repeat procedures, further contributing to healthcare cost reduction.

B) Impact on patients
In addition to potential long term healthcare benefit, short term impact on patients will be achieved by engaging patient groups in our research. Our research findings will be presented to patients through organised events but also to more specific patient groups undergoing VT ablation procedures.

C) Impact on general public
A range of public engagement activities (including organised events, use of social media, and release from the KCL press office) will be used to enhance general public awareness of our research findings but also to stimulate the curiosity and creativity of children/teenagers who will be the next generation of researchers.

D) Impact on industry
We believe industrial partnership is key in this project to ensure rapid clinical impact in this field. Our industrial partners will provide critical feedback to this project. The proposed technical innovations developed in this research will be made available to others sites to ensure maximum spread of the technique. The proposed technical developments also have potential to generate associated IP and will be first protected in consultation with the King's College IP & Licensing team.

E) Impact on UK research competitiveness
This research will also impact UK research competitiveness by maintaining an internationally leading MR-guided cardiac ablation programme at St' Thomas Hospital/KCL with a world leading expertise in CMR, cardiac electrophysiology, and CMR-guided procedures. This project has the potential to make CMR-guided VT ablation accessible throughout the UK by dissemination through academic, clinical and industrial links with other Trusts around the country that perform VT ablation procedures.

F) Impact on research communities
This research will generate knowledge in a multi-disciplinary fashion, both within the UK and internationally. This knowledge will benefit several communities including the engineering and image/signal processing communities, the CMR community, the cardiology/cardiac electrophysiology community.

G) Impact on team members
A range of activities will be conducted to ensure maximum impact on the career of the team members and to help them becoming independent researchers.