Evaluation of Fiberoptic Confocal Microscopy for Pediatric Cardiac Surgery

项目总结/摘要 我们的长期目标是建立实时光纤共聚焦显微镜（FCM）作为术中成像 在心脏手术中，特别是在儿科心脏直视手术中，心脏手术的一个主要风险是 传导系统受损，该系统负责启动电信号，快速传导 通过心脏同步机械激活传导系统的损伤与 具有显著的发病率并且（在极端情况下）需要昂贵的起搏器插入。尽管个别 由于传导系统的变化，手术期间对该组织的辨别目前仅限于视觉上的 解剖标志的识别。我们对几种动物模型和人体组织的初步研究 表明心脏组织显微图像提供了足够的信息用于视觉辨别 传导系统的组织和工作心肌。此外，我们确定了自动化方法， 基于显微图像的定量纹理分析的组织鉴别。在这个项目中，我们将 进一步开发这种实时成像模式和分析方法，以便临床医生可以使用这种方法 以避免对心脏传导系统的组织造成损伤。我们将评估我们的 在体外人心脏、新生儿心脏的体内绵羊模型以及最后在临床环境中的方法 在心脏直视手术中，通过三个特定的目标。在具体目标1中，我们将推进我们的方法， 正常和先天畸形心脏的心脏组织辨别力。我们将描述心房， 心室、窦房结、房室结和希氏束组织的三维重建 从传统的扫描共聚焦显微镜。这些研究将补充实时FCM 这些组织的图像。在特定目标2中，我们将评估实时FCM引导小儿心脏的能力， 使用心脏停搏液的新生儿心脏的绵羊模型进行手术。将进行组织成像 通过两种不同的染料输送技术;通过主动脉根部与局部表面应用。此外，本发明还 将被识别为传导系统的组织的组织解剖出来进行分析 验证。在具体目标3中，我们将研究接受淋巴结转移的患者体内结组织的微观结构。 心脏手术我们将首先在接受简单心脏外科手术的患者中研究这一点。 随后，我们将患者随机分为FCM成像组和标准手术修复组。我们将 研究术中使用FCM对术后传导异常发生率的影响。 我们假设使用FCM将有助于降低术后传导问题的发生率。所有 具体的目标是为了测试我们的假设，即实时FCM允许外科医生区分 在工作心肌和传导系统的组织之间。总之，拟议的研究 是将术中FCM转化为儿科心脏临床应用的关键一步 手术

PROJECT SUMMARY/ABSTRACT Our long-term aim is to establish real-time fiber-optics confocal microscopy (FCM) as an intraoperative imaging modality in cardiac surgery, particularly in pediatric open-heart surgery. A major risk of cardiac surgery is damage to the conduction system, which is responsible for initiating electrical signals, conducting them rapidly through the heart and synchronizing mechanical activation. Damage to the conduction system is associated with significant morbidity and (in extreme cases) necessitates costly pacemaker insertion. Despite individual variations in the conduction system, discrimination of this tissue during surgery is currently limited to the visual identification of anatomical landmarks. Our preliminary studies on several animal models and human tissue indicate that microscopic images of cardiac tissue provide sufficient information for visual discrimination of tissue of the conduction system and working myocardium. Furthermore, we identified automated methods for tissue discrimination based on quantitative texture analysis of microscopic images. In this project, we will further develop this real-time imaging modality and analysis methods so that clinicians can use the approach during surgical procedures to avoid damage to tissue of the cardiac conduction system. We will evaluate our approaches in explanted human hearts, in-vivo ovine model of neonatal hearts, and finally in the clinical setting during open-heart surgery through three Specific Aims. In Specific Aim 1, we will advance our approaches for cardiac tissue discrimination in normal and congenitally deformed human hearts. We will characterize atrial, ventricular, sinoatrial node, atrioventricular node and His bundle tissue using three-dimensional reconstructions from conventional scanning confocal microscopy. The studies will be complemented with real-time FCM imaging of these tissue. In Specific Aim 2, we will evaluate the ability of real-time FCM to guide pediatric heart surgery using an ovine model of the cardioplegic arrested neonatal heart. The tissue imaging will be performed by two different techniques of dye delivery; through the aortic root versus local surface application. Additionally, the tissue, which is identified as tissue of the conduction system will be dissected out for analysis and validation. In Specific Aim 3, we will study the microstructure of nodal tissues in-vivo in patients undergoing cardiac surgery. We will initially study this in patients undergoing a simple cardiac surgical procedure. Subsequently, we will randomize patients to FCM imaging versus standard surgical repair groups. We will investigate the impact of intraoperative FCM use on the incidence of postoperative conduction abnormalities. We hypothesize that using FCM will help decrease the incidence of postoperative conduction problems. All specific aims are designed towards testing our hypothesis that real-time FCM allows surgeons to discriminate between working myocardium and tissue of the conduction system. In summary, the proposed studies constitute a crucial step towards translation of intraoperative FCM for clinical application in pediatric heart surgery.