Endovascular Cardiac Optical Mapping

描述(申请人提供)：心律失常影响全国500多万人，每年导致120多万人住院和40万人死亡。心脏消融术的发展显著改善了治疗结果。消融传统上依赖于电解剖标测，这可能很繁琐，而且往往需要使用复杂的导航系统。即便如此，当前测绘模式的时空分辨率仍然很低。这些限制导致消融是一种高度专业化和昂贵的手术，只在选定的中心提供。此外，由于传统标测技术的局限性，消融效果在手术过程中难以评估。在初始手术时不能准确预测最终的成功会导致复发性心律失常和重复消融。与传统的电解剖标测工具相比，直接可视化导管提供了简单性，因为心脏解剖可以直接可视化，而不需要复杂的标测系统。然而，直接可视化导管的一个主要限制是不能直接标测电生理。例如，在用于房颤的肺静脉隔离中，尽管这在很大程度上是基于解剖学的过程，但仅靠直接可视化不能容易地促进生理定向消融(例如，基于复杂的心房分割电信号的消融或焦点转子的识别)。同样地，当对室性心动过速执行基质修改消融时，在视觉上识别消融目标是有问题的。此外，就像 传统的标测/消融系统不能直接验证消融效果，并且依赖于替代终点，如电传导阻滞，这些端点在术中可能会受到组织水肿的干扰。在这里，我们建议将直接可视化导管的简单方法与新颖、廉价和可扩展的电生理标测技术相结合，使用电压敏感荧光染料直观地显示解剖和电生理。特别是，在近红外光谱中发射的光稳定性染料可以进行优化，以实现安全的活体成像。该系统将适用于包括房颤在内的所有形式的心律失常，并承诺通过降低程序复杂性、程序时间和心律失常复发率来降低成本。在第一阶段期间，将实现以下三个具体目标：1.论证使用负担得起的发光二极管/单摄像机系统进行荧光成像的技术可行性。2.[建立优化的近红外电压敏感染料(S)临床使用的初步可利用性和安全性]3.论证球头血管内可视导管在活体动物体内微创光学映射比率电压的可行性。在随后的工作中，设备和染料设计将进一步优化，染料安全概况将得到更详细的表征，我们将完善动物模型的临床程序方法，软件分析方法将得到扩展，所有这些都将朝着商业化的最终目标迈进。

DESCRIPTION (provided by applicant): Cardiac arrhythmias affect more than 5 million people nationwide, resulting in more than 1.2 million hospitalizations and 400,000 deaths yearly. The development of cardiac ablation has significantly improved treatment outcomes. Ablation traditionally has relied on electroanatomic mapping which can be tedious and often requires the use of complex navigation systems. Even so, the spatiotemporal resolution of current mapping modalities remains low. These limitations cause ablation to be a highly specialized and costly procedure offered only at select centers. In addition, the effectiveness of ablation is difficult t evaluate during the procedure due to limitations of traditional mapping technologies. The inability to accurately predict ultimate success at the time of initial procedure leads to recurren arrhythmia and repeat ablations. Direct visualization catheters offer simplicity compared to traditional electroanatomic mapping tools in that cardiac anatomy can be directly visualized without the need for complex mapping systems. However, a major limitation of direct visualization catheters is that electrophysiology cannot be directly mapped. For example, in pulmonary vein isolation for atrial fibrillation, although this is largely an anatomically based procedure, direct visualization alone cannot readily facilitate physiologically directed ablation (e.g. ablation based on complex atrial fractionated electrograms or identification of focal rotors) Likewise, when performing substrate modification ablation for ventricular tachycardia, identification of ablation targets visually is problematic at best. Furthermore, as is the case for traditional mapping/ablation systems, ablation efficacy cannot be directly verified, and relies on surrogate endpoints such as electrical block which can be confounded intra-procedurally by tissue edema. Here we propose to combine the simpler approach of a direct visualization catheter with novel, inexpensive, and scalable electrophysiological mapping technology, using voltage sensitive fluorescent dyes to intuitively visualize both anatomy and electrophysiology. In particular, photostable dyes with emissions in the near-infrared spectrum can be optimized for safe in vivo imaging. This system will be applicable to all forms of arrhythmia, including atrial fibrillation, and promises to reduce costs by reducing procedural complexity, procedure time, and arrhythmia recurrence rates. During Phase I the following three specific aims will be addressed: 1. Demonstrate technical feasibility of fluorescence imaging using an affordable light-emitting- diode/single camera system. 2. [Establish preliminary deliverability and safety of optimized near-infrared voltage sensitive dye(s) for clinical use.] 3. Demonstrate the feasibility f a balloon-tipped endovascular visualization catheter to minimally invasively optically map ratiometric voltage in a live animal. In subsequent work, the device and dye designs will be further optimized, dye safety profile will be characterized in more detail, we will refine a clinicl procedural approach in animal models, and the software analysis approach will be expanded, all while pushing toward the ultimate goal of a commercial product.