Detection and Delineation of Necrotizing Fasciitis Via a Vascular Perfusion Fluorophore: A Pilot Study

Necrotizing fasciitis (NF)-commonly known as 'flesh-eating bacteria'-is an aggressive soft-tissue infection that has a high mortality rate (30-50%). NF is generally associated with traumatic inoculation of extremely aggressive bacteria into the soft-tissues surrounding the fascial layer of connective tissue, just deep to the subcutaneous fat. This tissue layer provides an ideal environment for bacterial growth and also facilitates rapid advancement of the bacteria along the fascia. The result is a soft-tissue infection that often spreads centrally prior to detection and/or adequate management, leading to systemic sepsis, multi-organ failure, and death.

Further complicating NF management is that there is no definitive diagnostic test. Patients with NF present generally with pain, fever, and elevated inflammatory labs (white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)), other lab abnormalities (elevated glucose and creatinine; reduced sodium and hemoglobin); however, these are non-specific findings that are associated with numerous other-nonfatal-conditions. For this reason, a diagnosis of NF is often missed until the condition has progressed too far.

Medical fluorescence is a nascent form of medical imaging that seeks to improve the recognition of important anatomical structures and disease processes through machine-assisted, visual identification using fluorescent probes called fluorophores. Several types of fluorophores exist: targeted fluorophores, enzyme-activated fluorophores, and simple intravascular fluorophores.

Intravascular fluorophores, primarily indocyanine green (ICG), have been available for ~100 years. ICG is FDA approved and has an excellent safety record with no demonstrable toxicity. When injected intravenously and viewed with an appropriate fluorescence imager, ICG effectively maps out the local vasculature, enabling the viewer to distinguish perfused and non-perfused tissues. ICG's FDA-approved indications and uses include angiography to determine cardiac output, hepatic function, liver blood flow, and ophthalmic anatomy.

Upon histological examination of tissues affected by NF, there exist four commonly observed features: 1) the presence of bacteria; 2) robust neutrophil infiltration; 3) tissue necrosis; 4) vascular thrombosis. DH-H Department of Pathology currently reviews tissue biopsies with respect to these criteria when evaluating tissue for the presence of necrotizing fasciitis (Soloman et al, Modern Pathology, 2018, pp 546-552). While useful to guide clinical decision-making, histological review is not considered to be a definitive diagnostic finding, but these observations do have moderate sensitivity and specificity with culture data, which is considered to be the ultimate determinant of an NF diagnosis.