Second-Window Indocyanine Green fluorescence imaging differentiates inflammation from necrotic tissue in early burn...

Subjective visual assessment to identify necrotic tissue in burns intraoperatively may lead to over-excision to avoid graft loss due to an inappropriately prepared wound bed. Second-Window Indocyanine Green (SWIG) is an emerging surgical guidance technique that harnesses an enhanced permeability and retention effect with a potential application in burn surgery. Using a mouse model of burn and inflammation, we show that SWIG has distinct fluorescence properties that differentiate inflammation and necrosis. To understand the underlying mechanisms behind SWIG, we functionally characterized tissue perfusion and permeability using indocyanine green (ICG) angiography in burn and inflamed tissue over time. We found that early burn hyperperfusion and permeability enhance ICG delivery to the wound bed for use in SWIG imaging. Using lipopolysaccharide (LPS) injection to induce non-burn inflammation, we found that ICG fluorescence varied depending on the mechanism driving inflammation, in addition to the necrosis-avid properties of SWIG. Similar to the current tumor-based clinical trials, the clinical potential of SWIG to provide objective, intraoperative guidance for precise burn excision of necrotic tissue will require optimization of ICG to disentangle the enhanced permeability and retention effect from the necrosis-avid properties of ICG.