Endovascular Cardiac Optical Mapping

描述（由申请人提供）：心律失常影响全国超过 500 万人，每年导致超过 120 万人住院，40 万人死亡。心脏消融术的发展显着改善了治疗效果。传统上的消融术依赖于电解剖测绘，这可能很乏味并且通常需要使用复杂的导航系统。即便如此，当前测绘方式的时空分辨率仍然很低。这些限制导致消融成为一种高度专业化且昂贵的手术，仅在选定的中心提供。此外，由于传统测绘技术的限制，在手术过程中很难评估消融的有效性。在初始手术时无法准确预测最终成功会导致心律失常复发和重复消融。 与传统的电解剖测绘工具相比，直接可视化导管更加简单，因为可以直接可视化心脏解剖结构，而不需要复杂的测绘系统。然而，直接可视化导管的一个主要限制是电生理学不能直接绘制。例如，在心房颤动的肺静脉隔离中，尽管这主要是基于解剖学的程序，但仅直接可视化并不能轻易促进生理定向消融（例如，基于复杂心房分割电图的消融或焦点转子的识别）。同样，当对室性心动过速进行基质修改消融时，目视识别消融目标充其量是有问题的。此外，正如情况 传统的标测/消融系统，消融效果无法直接验证，并且依赖于替代终点，例如电阻滞，这些电阻滞可能在手术中因组织水肿而混淆。 在这里，我们建议将直接可视化导管的更简单方法与新颖、廉价且可扩展的电生理图技术相结合，使用电压敏感荧光染料直观地可视化解剖学和电生理学。特别是，可以优化在近红外光谱中发射的光稳定染料，以实现安全的体内成像。该系统将适用于所有形式的心律失常，包括房颤，并有望通过降低手术复杂性、手术时间和心律失常复发率来降低成本。 在第一阶段，将实现以下三个具体目标： 1. 展示使用经济实惠的发光二极管/单相机系统进行荧光成像的技术可行性。 2. [确定用于临床使用的优化近红外电压敏感染料的初步输送能力和安全性。] 3. 证明气球尖端血管内可视化导管以微创光学方式绘制活体动物比例电压的可行性。 在后续工作中，设备和染料设计将进一步优化，染料安全性将得到更详细的表征，我们将完善动物模型中的临床程序方法，并且软件分析方法将得到扩展，同时推动商业产品的最终目标。

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.