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 组织坏死是由各种疾病和损伤引起的细胞死亡的一种形式。目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，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来改善烧伤中坏死的检测，以帮助围手术期临床决策。虽然吲哚菁绿色血管造影（ICGA）已被证明可以使用灌注作为坏死的替代标记物来识别烧伤深度，但它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显示出在图像引导的肿瘤手术切除中的前景。我们建议，ICGA和SWIG的联合成像可以用于提高烧伤以及许多涉及坏死的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手术，提高手术精度的关键需求，并提供炎症和坏死组织中ICG定位的见解。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。特定目标1将表征ICGA和SWIG在人类不确定深度烧伤愈合潜力中的荧光信号。特定目标2将评价术中荧光引导手术切除人类坏死组织的诊断准确性。Specific Aim 3将表征炎症、坏死和健康组织中的ICG荧光定量，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，包括一名烧伤外科医生科学家，他在人体热损伤模型方面具有丰富的经验，并在烧伤患者的手术护理方面具有临床专业知识，沿着成像专家，他们在开发用于体内成像的先进荧光技术方面有着良好的记录，包括称为“瞬时照明”的外科成像技术，其允许在环境照明条件下同时的白色光和低水平荧光可视化。瞬态照明在烧伤手术中尤其重要，以在全白色照明下用ICG荧光增强伤口的可视化。该项目将产生临床前和临床数据，测试ICG用于使用针对烧伤手术优化的荧光成像设备直接检测坏死组织的用途，同时开发用于量化组织坏死和表征ICG亲和性坏死的平台。这些研究将提供必要的数据，为设计更大规模的临床试验提供信息，以确定ICG荧光引导临床决策的有效性和有效性，从而改善烧伤患者的结局。