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

描述(由申请人提供)：这份建议书描述了一项为期五年的培训计划，旨在发展心脏电生理学的学术生涯。这位首席研究员长期以来一直对心脏电生理学研究感兴趣。在这笔赠款的过程中，申请者将获得培训和资金，以成为一名独立的研究人员，长期目标是了解心律失常的机制和开发新技术，从而产生更有效的治疗方案。在接下来的五年里，申请者将接受磁共振成像(MRI)技术和临床调查方面的正式教学培训。研究人员将由丹尼斯·帕克博士和一个由核磁共振研究、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指导。帕克博士是核磁共振研究领域的领导者，拥有独立的NIH资金和多年的指导经验。在本培训计划开始时，研究计划将专注于开发MRI可视化技术，以可视化消融病变集合中的间隙，目标是验证这样的假设，即准确地瞄准这些间隙将 带来更好的结果。房颤的消融成功率一直很低，可能需要多次手术，留下了显著改进的空间。大多数消融程序的目标是通过产生一系列组织烧伤或消融损伤，将具有电“触发源”的区域与易受此类触发源影响的组织隔离。要使这样的消融线路有效，这些线路应该没有缝隙。目前，还没有有效的方法来提供病变或消融成功路线的直接证据，对成功的评估依赖于间接标记物，而间接标记物往往不能很好地预测。核磁共振成像具有显示软组织的非凡能力。这些拟议的研究旨在开发基于MRI的技术，以可视化和评估射频消融损伤和病变集合中的靶点间隙。该项目的具体目标是：1)确定mri可以检测到的消融病变集合中的最小间隙，然后进行精确定位，2)检验假设，即准确识别和定位间隙将导致随着时间的推移在维持电气隔离方面的显著改善，以及3)检验在消融中mri检测到的间隙的假设 LINE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针对消融病变集合中的间隙的能力，从而显著改善消融手术的结果。此外，这些研究，核磁共振的教学培训，以及在此期间的临床调查和指导，将为申请者进行严格的假设检验研究做好准备。这些研究还将构成下一套房颤动物模型研究的基础，最后是在人类身上的研究。作为另一个资助项目的一部分，我们已经有了许多种类的大型房颤动物模型，这使得这项研究变得更加有吸引力。

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.