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

没有变化 项目简介：组织坏死是一种由多种疾病和损伤引起的细胞死亡形式。目前检测组织坏死以指导手术决策的方法有限。在烧伤中，组织坏死的临床可视化是护理的标准；然而，这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。迫切需要找到新的方法来改进烧伤坏死的检测，以辅助围手术期的临床决策。虽然吲哚青绿血管造影术(ICGA)已被证明可以用灌注量作为坏死的替代标志来识别烧伤深度，但它还没有被广泛应用于临床决策。最近，使用高剂量ICG(第二窗口吲哚青绿-斯威格)延迟成像的临床试验显示，在图像引导下的肿瘤手术切除方面前景光明。我们建议联合应用ICGA和SWIG成像技术来提高烧伤和许多涉及坏死的疾病过程中的手术决策。从这个项目中获得的知识将满足预防不必要的手术、提高手术精度的迫切需要，并为ICG在炎症和坏死组织中的定位提供洞察力。本项目的目标是在宏观和微观水平上表征烧伤炎症和坏死中的ICGA和SWIG荧光。具体目标1将描述来自ICGA和SWIG的荧光信号在人类无限深度烧伤的愈合潜力中的特征。具体目标2将评估术中荧光引导手术切除人类坏死组织的诊断准确性。具体目标3将描述炎症、坏死和健康组织中ICG荧光定量的特征，并使用细胞培养和动物模型确定底物定位。为了实现我们的目标，我们将使用团队科学方法，其中包括一名在人体热损伤模型方面拥有丰富经验的烧伤外科科学家，以及在烧伤患者外科护理方面拥有临床专业知识的成像专家，他们在开发先进的基于荧光的活体成像技术方面有着良好的记录，包括一种名为“瞬变照明”的外科成像技术，该技术允许在环境照明条件下同时进行白光和低水平荧光可视化。瞬时光在烧伤手术中尤其重要，在全白光下用ICG荧光增强创面的可视化。该项目将产生临床前和临床数据，测试使用ICG直接检测坏死组织的使用，使用针对烧伤手术优化的荧光成像设备，同时开发一个量化组织坏死和ICG-Avid坏死特征的平台。这些研究将为设计一项更大规模的临床试验提供必要的数据，以确定ICG荧光引导的临床决策的有效性和有效性，以改善烧伤患者的预后。

No changes 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 combined imaging with ICGA and SWIG 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 ICGA and SWIG fluorescence in burn inflammation and necrosis on a macroscopic and microscopic level. Specific Aim 1 will characterize fluorescent signals from ICGA and SWIG in the healing potential of indeterminate depth burns in humans. Specific Aim 2 will evaluate the diagnostic accuracy of intraoperative fluorescence-guided surgical resection of necrotic tissue in humans. Specific Aim 3 will characterize ICG fluorescence quantification in inflamed, necrotic, and healthy tissues and determine substrate localization using cell culture and animal models. 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 the use 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.