MRI-based visualization and acute targeting of gaps in atrial ablation lesions

描述（由申请人提供）：本提案描述了一个为期五年的培训计划，以发展心脏电生理学的学术生涯。主要研究者对心脏电生理学研究有着长期的兴趣。在此期间，申请人将获得培训和资金，成为一名独立的研究人员，其长期目标是了解心律失常机制和开发新技术，从而获得更有效的治疗方案。在接下来的五年里，申请人将接受磁共振成像（MRI）技术和临床研究的正式教学培训。研究者将由Dennis帕克博士以及由MRI研究、临床电生理学、图像处理和生物统计学领域的专家组成的委员会沿着指导。帕克博士是MRI研究领域的领导者，拥有独立的NIH资助和多年的指导经验。在该培训计划开始时，研究计划将重点开发MRI可视化技术，以可视化消融病变组中的间隙，目的是测试以下假设： 导致更好的结果。房颤消融术的成功率仍然持续较低，可能需要多次手术，这为显著改善留下了空间。这些消融手术中的大多数的目标是通过产生组织烧伤或消融损伤线来将具有电“触发”源的区域与易受这种触发影响的组织隔离。为了使这种消融线有效，这些线应该没有间隙。目前，没有有效的手段来提供损伤或消融的成功线的直接证据，并且成功的评价依赖于间接标记物，这些间接标记物通常是较差的预测因子。MRI具有可视化软组织的特殊功能。这些拟议的研究旨在开发基于MRI的技术，以可视化和评价射频消融病变和病变组中的靶间隙。本项目的具体目的是：1）确定MRI可检测到的消融病变组中的最小间隙，然后立即定位，2）测试以下假设：立即识别和定位间隙将导致随着时间的推移维持电隔离的显著改善，以及3）测试以下假设：消融中MRI检测到的间隙 线将预测人类的电重新连接和心律失常复发。这些研究的成功将极大地扩展我们在消融损伤组中定位间隙的能力，从而改善消融手术的结局。此外，在此期间，这些研究，MRI教学培训，临床调查和指导，将使申请人准备进行严格的假设检验研究。这些研究也将成为下一组房颤动物模型研究的基础，最后是人类研究。作为另一个资助项目的一部分，我们已经有了一些房颤的大型动物模型，这使得这项研究更具吸引力。

DESCRIPTION (provided by applicant): 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.