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: 10652537
• 负责人: ANGELA L F GIBSON
• 金额: $ 28.06万
• 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/10652537
• 关键词: Adopted; Angiography; Animal Model; Area; Blood capillaries; Body Surface Area; Burn injury; Caring; Cause of Death; Cell Culture Techniques; Cell Death; Cellular Infiltrate; Cicatrix; Clinical; Clinical Data; Clinical Trials; Darkness; Data; Decision Making; Detection; Disease; Dose; Early Intervention; Evaluation; Excision; Excretory function; Feasibility Studies; Fluorescence; Goals; Half-Life; Hemorrhage; Histologic; Human; Image; Image-Guided Surgery; Imaging Device; Imaging technology; In Vitro; Indocyanine Green; Inferior; Inflammation; Inflammatory; Injury; Knowledge; Life; Light; Lighting; Malignant Neoplasms; Measures; Methods; Microscopic; Modeling; Mus; Necrosis; Operative Surgical Procedures; Outcome; Pain; Patient Admission; Patients; Perfusion; Perioperative; Process; Quality of life; Regenerative capacity; Science; Scientist; Sensitivity and Specificity; Signal Transduction; Soft Tissue Infections; Surgeon; Surrogate Markers; Techniques; Technology; Testing; Tissue Viability; Tissues; Tourniquets; Unnecessary Surgery; Visual; Visualization; biomarker identification; burn model; chronic wound; clinical decision-making; design; detection method; diagnostic accuracy; efficacy evaluation; experience; fluorescence imaging; fluorescence-guided surgery; healing; heat injury; improved; improved outcome; in vivo; in vivo imaging; injured; insight; interest; mouse model; necrotic tissue; novel; pre-clinical; preservation; prevent; randomized, clinical trials; skin xenograft; standard of care; systemic inflammatory response; tissue injury; trial comparing; tumor; wound; wound healing

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.

没有变化 项目摘要：组织坏死是由多种疾病和伤害引起的细胞死亡形式。当前检测组织坏死以指导手术决策的方法是有限的。在烧伤损伤中，组织坏死的临床可视化是护理标准。但是，这是一种浸渍方法，可以导致护理延迟，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，以帮助定期临床决策。虽然已证明吲哚氨酸绿色血管造影（ICGA）可以使用灌注作为坏死的替代标记，但并未被广泛用于临床决策。最近，使用高剂量ICG的延迟成像（第二窗吲哚烷绿色 - SWIG）的临床试验显示出在图像引导的手术切除肿瘤中的希望。我们建议，可以使用ICGA和SWIG组合成像来增强烧伤损伤的手术决策以及许多涉及坏死的疾病过程。从该项目中获得的知识将满足防止不必要的手术，提高手术精度并深入了解ICG在发炎和坏死组织中的定位的关键需求。该项目的目的是表征ICGA和SWIG荧光在烧伤感染和宏观和微观水平上的坏死。特定的目标1将表征来自ICGA和SWIG的荧光信号，这是人类不确定深度燃烧的愈合潜力。具体目标2将评估人类坏死组织术中荧光引导的手术切除的诊断准确性。特定的目标3将表征ICG荧光定量在发炎，坏死和健康组织中，并使用细胞培养和动物模型确定底物定位。为了满足我们的目标，我们将采用一种团队科学方法，包括一位在人体热损伤模型中拥有丰富经验的外科医生科学家，并在烧伤患者的手术护理中具有丰富的经验，以及具有开发基于先进荧光的体内图像技术的高级荧光技术的成像专家，包括手术成像技术，包括“瞬时照明”的灯光和同时的灯光效果。瞬态照明对于在全白色照明下使用ICG荧光的伤口可视化而燃烧手术尤其重要。该项目将导致临床前和临床数据测试ICG使用用于优化烧伤手术的荧光成像装置直接检测坏死组织的，同时开发了定量组织坏死的平台和ICG-避免了ICG-避免avid avid坏死的表征。这些研究将提供必要的数据，以告知大型临床试验的设计，以确定ICG荧光引导的临床决策的效率和有效性，以改善烧伤患者的预后。