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

组织坏死是由多种疾病引起的细胞死亡的一种形式， 受伤目前检测组织坏死以指导手术决策的方法是有限的。烧伤 损伤，组织坏死的临床可视化是护理标准;然而，这是一种不精确的方法， 可能导致护理延迟、不必要的手术和切除活组织。迫切需要 确定新的方法，以提高烧伤坏死的检测，以帮助围手术期的临床决策 制作。虽然吲哚菁绿色血管造影（ICGA）已被证明可以使用灌注来识别烧伤深度 作为坏死的替代标记物，其尚未被广泛用于临床决策。最近， 使用高剂量ICG（第二窗口吲哚菁绿色- SWIG）的延迟成像的临床试验已经 在肿瘤的图像引导手术切除中显示出前景。我们建议SWIG成像可以 用于加强烧伤以及许多疾病过程中的手术决策 包括坏死。从这个项目中获得的知识将满足防止不必要的 手术，提高手术精度，并提供炎症和坏死组织中ICG定位的洞察。 本项目的目标是表征SWIG荧光在烧伤炎症和坏死的一个 宏观和微观层面。特异性目标1将表征来自SWIG的荧光信号， 人类不确定深度烧伤的治愈潜力。具体目标2将检查关联 SWIG荧光与手术切除烧伤坏死深度之间的关系。具体目标3将量化 炎症、坏死和健康人体细胞和组织中的ICG荧光，以确定底物 本地化为了实现我们的目标，我们将使用团队科学方法，包括烧伤外科医生科学家， 在人体热损伤模型方面具有丰富的经验，在烧伤外科护理方面具有临床专业知识 患者沿着成像专家，他们有开发先进的基于荧光的 用于体内成像的技术，包括称为“瞬时照明”的外科成像技术， 在环境照明条件下同时显示白色光和低水平荧光。瞬态 在烧伤手术中，照明对于用ICG荧光增强伤口的可视化尤其重要 在全白色照明下。 该项目将导致ICG用于直接检测坏死组织的临床前和临床数据测试 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， 和ICG亲和性坏死的表征。这些研究将提供必要的数据， 通知设计一个更大的临床试验，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.