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

基于荧光的炎症和坏死检测，为手术决策提供信息并提高结果

• 批准号: 10797980
• 负责人: ANGELA L F GIBSON
• 金额: $ 20.12万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10797980
• 关键词: Adopted; Angiography; Area; Binding; Biopsy; Blood capillaries; Burn injury; Caring; Cause of Death; Cell Culture Techniques; Cell Death; Cells; Cellular Infiltrate; Characteristics; Cicatrix; Clinical; Clinical Data; Clinical Trials; Data; Decision Making; Detection; Disease; Dose; Early Intervention; Evaluation; Excision; Feasibility Studies; Flow Cytometry; Fluorescence; Functional disorder; Goals; Half-Life; Hemorrhage; Histologic; Human; Image; Image-Guided Surgery; Imaging Device; Imaging technology; In Vitro; Indocyanine Green; Inferior; Inflammation; Inflammatory; Inflammatory Response; Injury; Judgment; Knowledge; Life; Light; Lighting; Malignant Neoplasms; Methods; Microscopic; Modeling; Necrosis; Operative Surgical Procedures; Outcome; Pain; Patient Admission; Patient-Focused Outcomes; Patients; Perfusion; Perioperative; Process; Quality of life; Regenerative capacity; Reproducibility; Science; Scientist; Signal Transduction; Soft Tissue Infections; Surgeon; Surrogate Markers; Techniques; Technology; Testing; Thick; Tissue Viability; Tissues; Tourniquets; Training; Unnecessary Surgery; Visual; Visualization; biomarker identification; burn model; chronic wound; clinical decision-making; design; detection method; efficacy evaluation; experience; fluorescence imaging; fluorescence-guided surgery; healing; heat injury; image guided; improved; improved outcome; in vivo; in vivo imaging; insight; interest; mouse model; necrotic tissue; novel; patient subsets; pre-clinical; preservation; prevent; randomized, clinical trials; skin xenograft; standard of care; tissue injury; trial comparing; tumor; wound; wound healing

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.

项目摘要：组织坏死是由多种疾病和 受伤。当前检测组织坏死以指导手术决策的方法是有限的。在烧伤中 损伤，组织坏死的临床可视化是护理标准。但是，这是一种暗示的方法 可能导致护理延迟，不必要的手术和去除可行的组织。迫切需要 确定新的方法来改善烧伤损伤中坏死的检测以帮助周期性临床决策 制作。虽然已证明吲哚氨酸绿色血管造影（ICGA）可以使用灌注来识别燃烧深度 作为坏死的替代标记，临床决策并未被广泛采用。最近， 使用高剂量ICG的延迟成像（第二窗吲哚烷绿色-SWIG）的临床试验具有 在图像引导的肿瘤手术切除术中显示了有希望。我们建议Swig成像可以 用于增强烧伤中的手术决策以及在许多疾病过程中 涉及坏死。从该项目中获得的知识将满足防止不必要的关键需求 手术，提高手术精度，并洞悉发炎和坏死组织中的ICG定位。 该项目的目的是表征在烧伤注射和坏死中的SWIG荧光 宏观和微观水平。特定的目标1将表征来自Swig的荧光信号 不确定深度燃烧的治愈潜力在人类中燃烧。特定目标2将检查协会 在SWIG荧光和在手术出色的烧伤中坏死深度之间。特定目标3将量化 发炎，坏死和健康的人类细胞和组织中的ICG荧光，以确定底物 本土化。为了实现我们的目标，我们将使用包括烧伤外科医生科学家在内的团队科学方法 在人体热损伤模型和临床专业知识方面具有丰富的经验 患者以及成像专家，他们具有发展高级荧光的往绩 体内成像的技术，包括一种称为“瞬态照明”的外科成像技术，该技术允许 在环境照明条件下，简单的白光和低级荧光可视化。瞬态 照明对于烧伤手术尤其重要，以增强ICG荧光的伤口可视化 在完整的白色照明下。 该项目将导致ICG的临床前和临床数据测试直接检测坏死组织 使用用于烧伤手术的荧光成像装置，同时开发定量平台 组织坏死的组织坏死的表征。这些研究将提供必要的数据 告知大型临床试验的设计，以确定ICG荧光引导的效率和有效性 临床决策以改善烧伤患者的预后。