Photoacoustic Imaging to Guide Catheter Ablation of Cardiac Arrhythmias

项目摘要 导管消融（CA）是几乎所有心律失常的潜在治愈性治疗，但临床结果 仍然不理想，导致重复手术。如果所有消融靶点都能 以及是否可以确定消融损伤的耐久性和连续性的实时评估。 这些基本的知识差距可以通过应用光谱光声成像来克服 （sPAI）技术在术中指导和监测CA。sPAI可以提供对组织表征的深入了解 以及基于组织的波长相关光学吸收差异的消融损伤。通过靶向 血红蛋白（总血红蛋白、脱氧血红蛋白和氧合血红蛋白）和吸水性差异，灌注/活组织沿着 可以确定局部组织氧饱和度（StO 2）和水含量。这种成像的深度可以 超越了心脏的心内膜或心外膜表面，并提供了 心脏的“中间心肌”区域，其目前通过当前的标测技术是未知的。以前的工作 我们的小组已经表明sPAI可以提供热消融范围和深度的实时定量。这些 临床医生使用的现有技术目前无法获得数据。因此，我们的目标 研究是开发和验证实时sPAI技术，评估组织氧饱和度（StO 2），总 血红蛋白和水含量，以1）识别和区分存活心肌与瘢痕的区域，以及2） 确定永久消融的组织与暂时“受伤”但仍存活的心肌。这种能力 有望确定新的消融靶点，这将直接改善CA的结果。当前方法 通常不能直接识别CA的更深的“中层心肌”靶点， 这些区域基于操作者经验和/或先前失败的过程。sPAI有能力 第一次制定了一个标准化的工作流程，以确定何时以及如何瞄准目前难以访问的目标， 心肌的区域。这将对CA成功率产生深远的临床影响，同时减少 手术并发症我们打算通过首先优化sPAI技术来实现这些目标， 体外心室组织中的超声（US）掺入。这将决定所需的规格， 最佳的（例如，最大深度穿透和StO 2精度）组织成像。随后的工作将 专注于使用开胸猪模型优化基于sPAI的体内心肌组织表征 梗死模型。我们打算识别存活心肌和瘢痕区域，并与大体配准的 MRI和独立组织病理学评估。最后，在这些初步实验的基础上，我们打算 区分永久消融组织与周围水肿（“损伤”）和正常心肌组织 在开胸的猪模型中。实现这些目标将为基于导管的sPAI指导铺平道路 在CA期间进行监控，在该领域创造了一个重大的范式转变， 患者结局。

Project Summary Catheter ablation (CA) is a potentially curative treatment for nearly all cardiac arrhythmias, yet clinical outcomes remain suboptimal, leading to repeat procedures. Success rates would improve if all targets for ablation could be identified and if real-time assessment of the durability and continuity of ablation lesions could be determined. These fundamental gaps in knowledge could be overcome by applying spectroscopic photoacoustic imaging (sPAI) techniques to intraoperatively guide and monitor CA. sPAI can provide insight into tissue characterization and ablation lesions based on wavelength-dependent optical absorption differences of tissue. By targeting hemoglobin (total, deoxy-, and oxy-hemoglobin) and water absorption differences, perfused/viable tissue along with local tissue oxygen saturation (StO2) and water content can be determined. The depth of this imaging can go beyond the endocardial or epicardial surfaces of the heart and provide novel tissue characterization in the “mid-myocardial” region of the heart, which is presently unknown via current mapping techniques. Prior work by our group has shown that sPAI can provide real-time quantification of thermal ablation extent and depth. These data are currently unavailable with existing technologies used by clinicians. Consequently, the goal of our research is to develop and validate real-time sPAI techniques assessing tissue oxygen saturation (StO2), total hemoglobin, and water content to 1) identify and differentiate regions of viable myocardium versus scar and 2) determine permanently ablated tissue versus temporarily “injured” yet still viable myocardium. Such a capability promises to identify novel targets for ablation, which would directly improve CA outcomes. Current approaches often cannot directly identify deeper “mid-myocardial” targets for CA and adjunctive ablation techniques to target these regions are based either on operator experience and/or prior failed procedures. sPAI would have the ability to create—for the first time—a standardized workflow for when and how to target currently difficult to access regions of the myocardium. This would have profound clinical implications for CA success rates while reducing procedural complications. We intend to accomplish these aims by first optimizing sPAI techniques with ultrasound (US) incorporation in ex-vivo ventricular tissue. This will determine the specifications needed for optimal (e.g., maximal depth penetration and StO2 accuracy) tissue imaging. Subsequent work will then be focused on optimization of in-vivo, sPAI-based, myocardial tissue characterization using an open-chest porcine infarct model. We intend to identify regions of viable myocardium and scar and validate with grossly co-registered MRI and independent histopathologic assessment. Finally, building on these initial experiments, we intend to differentiate permanently ablated tissue from surrounding edematous (“injured”) and normal myocardial tissue in an open-chest, porcine model. Achieving these goals would pave the way for catheter based sPAI guidance and monitoring during CA, creating a significant paradigm shift in the field with the ability to dramatically improve patient outcomes.