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疾病引起的细胞死亡的一种形式。 目前在烧伤中检测组织坏死以指导手术决策的方法是有限的。 损伤时，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、不必要的手术以及活组织的切除，因此迫切需要这样做。 确定改进烧伤坏死检测的新方法，以帮助围手术期临床决策 而吲哚菁绿血管造影 (ICGA) 已被证明可以通过灌注来确定烧伤深度。 作为坏死的替代标志物，它最近尚未广泛应用于临床决策。 使用高剂量 ICG 延迟成像（第二窗口吲哚菁绿 - SWIG）的临床试验已 我们建议 SWIG 成像在图像引导的肿瘤手术切除中显示出前景。 用于增强烧伤以及许多疾病过程中的手术决策 从该项目中获得的知识将满足防止不必要的坏死的关键需求。 手术，提高手术精度，并深入了解 ICG 在发炎和坏死组织中的定位。 该项目的目标是表征烧伤炎症和坏死中的 SWIG 荧光 具体目标 1 将表征来自 SWIG 的荧光信号。 具体目标 2 将检查人类不确定深度烧伤的治愈潜力。 具体目标 3 将量化 SWIG 荧光与手术切除烧伤的坏死深度之间的关系。 发炎、坏死和健康人体细胞和组织中的 ICG 荧光以确定底物 为了实现我们的目标，我们将采用团队科学方法，其中包括一名烧伤科学家外科医生。 在人体热损伤模型方面拥有丰富的经验，在烧伤外科护理方面拥有丰富的临床专业知识 患者以及具有开发先进荧光技术记录的成像专家 体内成像技术，包括称为“瞬态照明”的外科成像技术，该技术允许 在瞬态照明条件下同时进行白光和低水平荧光可视化。 照明在烧伤手术中尤其重要，可以通过 ICG 荧光增强伤口的可视化 在全白光照明下。 该项目将进行 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 这些研究将为组织坏死的发生和 ICG 坏死的特征提供必要的数据。 为更大规模的临床试验的设计提供信息，以确定 ICG 荧光引导的功效和有效性 改善烧伤患者预后的临床决策。