This proposal describes a five-year training program to develop an academic career in cardiac electrophysiology. The principal investigator has a long-standing interest in cardiac electrophysiology research. Over the course of this grant, the applicant will obtain the training and funding to become an independent investigator with the long-term goal of understanding arrhythmia mechanisms and developing new technologies, leading to more efficacious treatment regimens. Over the next five years the applicant will undergo formal didactic training in Magnetic Resonance Imaging (MRI) techniques and clinical investigation. The investigator will be mentored by Dr. Dennis Parker, along with a committee comprised of experts in the field of MRI research, clinical electrophysiology, image processing and biostatistics. Dr. Parker is a leader in the field of MRI research with independent NIH funding and many years of mentoring experience. At the onset of this training program, the research program will be focused on developing MRI visualization techniques to visualize gaps in ablation lesion sets with the goal to test the hypothesis that targeting these gaps acutely will lead to improved outcomes. The success rate for ablation in atrial fibrillation remains persistently low and can require multiple procedures, leaving room for significant improvement. The goal in most of these ablation procedures is to isolate a region with sources of electrical "triggers" from tissue susceptible to such triggers by creating a line of tissue burns or ablation lesions. For such ablation lines to be effective, the lines should have no gaps. Currently, there i no effective means to provide direct proof of successful lines of lesion or ablation and the evaluation of success depends on indirect markers that are often poor predictors. MRI has exceptional capabilities for visualizing soft tissue. These proposed studies aim to develop MRI-based techniques to visualize and evaluate radiofrequency ablation lesions and target gaps in lesion sets.
The specific aims for this project are: 1) to determine the smallest gap in ablation lesion sets that can be detected by MRI and then targeted acutely, 2) to test the hypothesis that identifying and targeting gaps acutely will lead to significant improvement in maintaining electrical isolation over time, and 3) to test the hypothesis that gaps detected by MRI in ablation lines will predict electrical reconnection and arrhythmia recurrence in humans. Success in these studies will greatly expand our ability to target gaps in ablation lesion sets acutely leading to improved outcomes from ablation procedures. Moreover, these studies, didactic training in MRI, and clinical investigation and mentoring during this period, will prepare the applicant to pursue rigorous hypothesis testing research. These studies will also form the basis of the next set of studies in animal models of atrial fibrillation, and finally, in humans. We already have a number of species of large animal models of atrial fibrillation as part of another funded project, which makes this research all the more attractive.
The recurrence rate of arrhythmias after catheter ablation procedures remains high. This proposal investigates the role of gaps in ablation lesions in the poor outcome and examines if acutely targeting them will lead to significant improvement in outcomes.
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|Kholmovski, Eugene G; Coulombe, Nicolas; Silvernagel, Joshua et al. (2016) Real-Time MRI-Guided Cardiac Cryo-Ablation: A Feasibility Study. J Cardiovasc Electrophysiol 27:602-8|
|Parmar, Bhrigu R; Jarrett, Tyler R; Kholmovski, Eugene G et al. (2015) Poor scar formation after ablation is associated with atrial fibrillation recurrence. J Interv Card Electrophysiol 44:247-56|
|Angel, Nathan; Li, L I; Macleod, Rob S et al. (2015) Diverse Fibrosis Architecture and Premature Stimulation Facilitate Initiation of Reentrant Activity Following Chronic Atrial Fibrillation. J Cardiovasc Electrophysiol 26:1352-60|
|Ranjan, Ravi; McGann, Christopher J; Jeong, Eun-Kee et al. (2015) Wideband late gadolinium enhanced magnetic resonance imaging for imaging myocardial scar without image artefacts induced by implantable cardioverter-defibrillator: a feasibility study at 3 T. Europace 17:483-8|
|Ranjan, Ravi; Dosdall, Derek; Norlund, Layne et al. (2014) Diagnostic imaging and pacemaker implantation in a domestic goat with persistent left cranial vena cava. J Vet Cardiol 16:45-50|
|Blauer, Joshua J E; Swenson, Darrell; Higuchi, Koji et al. (2014) Sensitivity and specificity of substrate mapping: an in silico framework for the evaluation of electroanatomical substrate mapping strategies. J Cardiovasc Electrophysiol 25:774-80|
|Bassett, Elwin C; Kholmovski, Eugene G; Wilson, Brent D et al. (2014) Evaluation of highly accelerated real-time cardiac cine MRI in tachycardia. NMR Biomed 27:175-82|
|Parmar, Bhrigu R; Jarrett, Tyler R; Burgon, Nathan S et al. (2014) Comparison of left atrial area marked ablated in electroanatomical maps with scar in MRI. J Cardiovasc Electrophysiol 25:457-63|
|Higuchi, Koji; Akkaya, Mehmet; Koopmann, Matthias et al. (2013) The effect of fat pad modification during ablation of atrial fibrillation: late gadolinium enhancement MRI analysis. Pacing Clin Electrophysiol 36:467-76|
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