Fluorescence-based detection of inflammation and necrosis to inform surgical decision-making and enhance outcomes

项目摘要：组织坏死是一种细胞死亡形式，由多种疾病和 受伤。目前检测组织坏死以指导手术决策的方法有限。在燃烧中 损伤、组织坏死的临床可视化是护理的标准；然而，它是一种不精确的方法 可能会导致护理延误、不必要的手术和活组织的移除。迫切需要 寻找新的方法改进烧伤坏死的检测，以辅助围手术期的临床决策 制作。而吲哚青绿血管造影术(ICGA)已被证明可以通过灌流来确定烧伤深度 作为坏死的替代标记物，它还没有被广泛应用于临床决策。最近， 使用大剂量ICG(第二窗口吲哚青绿灌胃)延迟成像的临床试验 在影像引导下的肿瘤手术切除方面显示出良好的前景。我们建议SWIG成像可以 用于加强烧伤和许多疾病过程中的手术决策 涉及坏死的。从这个项目中获得的知识将满足防止不必要的迫切需要 手术，提高手术精度，并提供对ICG在炎症和坏死组织中的定位的洞察。 这个项目的目标是描述烧伤炎症和坏死中的强烈荧光特征。 宏观层面和微观层面。特定目标1将描述来自SWIG的荧光信号 人类不明深度烧伤的治愈潜力。《特定目标2》将考察两者之间的关联 在手术切除的烧伤中，大量的荧光和坏死深度之间的关系。具体目标3将量化 在炎症、坏死和健康的人体细胞和组织中测定底物的ICG荧光 本地化。为了实现我们的目标，我们将使用团队科学的方法，包括一名烧伤外科科学家 拥有丰富的人体热损伤模型经验和烧伤外科治疗方面的临床经验。 患者以及有开发基于高级荧光技术的记录的成像专家 活体成像技术，包括一种名为“瞬变光”的外科成像技术，它可以 在环境照明条件下同时显示白光和低水平荧光。瞬变 在烧伤手术中，照明尤其重要，以增强ICG荧光对伤口的可见性 在全白光下。 该项目将导致ICG的临床前和临床数据测试，以直接检测坏死组织 使用针对烧伤手术优化的荧光成像设备，同时开发量化平台 组织坏死和ICG-Avid坏死的特征。这些研究将提供必要的数据，以 通知设计一项更大的临床试验，以确定ICG荧光引导的疗效和有效性 临床决策，以改善烧伤患者的预后。

Project Summary: Tissue necrosis is a form of cell death caused by a wide variety of diseases and injuries. Current methods of detecting tissue necrosis to guide surgical decision making are limited. In burn injury, clinical visualization of tissue necrosis is the standard of care; however, it is an imprecise method that can result in delays in care, unnecessary surgery, and removal of viable tissue. There is a critical need to identify novel methods to improve the detection of necrosis in burn injury to aid perioperative clinical decision making. While Indocyanine Green Angiography (ICGA) has been shown to identify burn depth using perfusion as a surrogate marker for necrosis, it has not been widely adopted for clinical decision making. Recently, clinical trials using delayed imaging of high dose ICG (Second Window Indocyanine Green - SWIG) have shown promise in image-guided surgical resection of tumors. We propose that SWIG imaging can be employed to enhance surgical decision-making in burn injury, as well as in many disease processes involving necrosis. The knowledge gained from this project will fill the critical need to prevent unnecessary surgery, improve surgical precision, and provide insight into ICG localization in inflamed and necrotic tissue. The goal of this project is to characterize the SWIG fluorescence in burn inflammation and necrosis on a macroscopic and microscopic level. Specific Aim 1 will characterize fluorescent signals from SWIG in the healing potential of indeterminate depth burns in humans. Specific Aim 2 will examine the association between SWIG fluorescence and depth of necrosis in surgically excised burns. Specific Aim 3 will quantify ICG fluorescence in inflamed, necrotic, and healthy human cells and tissues to determine substrate localization. To attain our goal, we will use a team science approach including a burn surgeon scientist who has extensive experience in human thermal injury models and clinical expertise in the surgical care of burn patients along with imaging experts who have a track record for developing advanced fluorescence-based technologies for in vivo imaging, including a surgical imaging technology called “transient lighting” that allows simultaneous white light and low-level fluorescence visualization in ambient lighting conditions. Transient lighting is especially critical in burn surgery to augment the visualization of the wound with ICG fluorescence under full white lighting. This project will result in preclinical and clinical data testing of ICG for direct detection of necrotic tissue using a fluorescence imaging device optimized for burn surgery, while developing a platform for quantification of tissue necrosis and characterization of ICG-avid necrosis. These studies will provide necessary data to inform the design of a larger clinical trial to determine the efficacy and validity of ICG fluorescence-guided clinical decision making to improve outcomes for burn patients.