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

University Of Wisconsin-Madison, Madison WI

Investigators

Linked publications & trials

Abstract

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 imageguided surgical resection of tumors. We propose that fluorescent imaging with ICGA and SWIG and a novel endogenous fluorophore 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 fluorescence 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 and explore the novel use of protoporphyrin as an endogenous fluorophore. 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 fluorescence quantification and microenvironmental gene expression 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. These studies will provide foundational data to inform the design of a randomized clinical trial comparing fluorescence-based burn excision to the current standard of care. Quantification of fluorescence and correlation to inflammation and necrosis will support applications of fluorescence-guided surgery in diseases, including cancer, soft tissue infections, and chronic wounds.