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.
Because of the profound pro-thrombotic effects of necrotizing fasciitis within the
subcutaneous tissues, we hypothesize that the administration of ICG and subsequent
imaging of a bodily region affected with NF will demonstrate substantially reduced
fluorescence compared to the patient's unaffected tissues. If we can demonstrate that ICG
fluorescence voids are characteristic of NF, this could potentially lead to a more rapid,
and potentially more accurate, diagnosis of NF that would lead to more rapid definitive
management and-likely-improved outcomes.
The goal of this pilot study is to evaluate whether ICG fluorescence may be used as a
non-invasive method of identifying the presence of NF.