Evaluation of Fiberoptic Confocal Microscopy for Pediatric Cardiac Surgery

项目摘要/摘要 我们的长期目标是建立实时光纤共焦显微镜(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 对负责启动电信号、快速传导电信号的传导系统造成损害 通过心脏和同步的机械激活。传导系统的损伤与 有严重的发病率，(在极端情况下)需要安装昂贵的起搏器。尽管个人 传导系统的变化，手术中对这一组织的辨别目前仅限于视觉 解剖地标的识别。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 传导系统和工作心肌的组织。此外，我们确定了自动化方法，以 基于显微图像定量纹理分析的组织识别。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该方法 在外科手术中，以避免心脏传导系统的组织受损。我们将评估我们的 移植人心脏、活体绵羊新生心脏模型以及临床应用的方法 在心内直视手术期间，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 正常人和先天畸形心脏的心脏组织辨别。我们将描述心房的特征， 应用三维重建技术重建心室、窦房结、房室结和希氏束组织 来自传统的扫描共聚焦显微镜。这些研究将得到实时FCM的补充 对这些组织进行成像。在具体目标2中，我们将评估实时FCM对儿童心脏的指导能力 手术使用的是一种停跳的绵羊模型，新生儿心脏骤停。将进行组织成像 通过两种不同的染料输送技术；通过主动脉根部和局部表面涂抹。另外， 被确认为传导系统组织的组织将被解剖出来进行分析和 验证。在特定的目标3中，我们将研究患者体内结节组织的微结构。 心脏手术。我们最初将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。我们会 研究术中应用FCM对术后传导异常发生率的影响。 我们假设使用FCM将有助于减少术后传导问题的发生率。全 特定的目的是为了验证我们的假设，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。总括而言，拟议的研究 为术中FCM在儿科心脏的临床应用迈出了关键的一步 做手术。

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.