Mechanisms of delayed indocyanine green fluorescence and applications to clinical disease processes

Delayed indocyanine green fluorescence imaging is under investigation in various clinical disease processes. Understanding the mechanisms of indocyanine green accumulation and retention is essential to correctly interpreting and analyzing imaging data. The purpose of this scoping review was to synthesize what is known about the mechanism of indocyanine green retention at the cellular level to better understand the clinical nuances of delayed indocyanine green imaging and identify critical gaps in our knowledge to guide future studies.

We performed a scoping review of 7,087 citations after performing database searches of PubMed, Scopus, the Cochrane Library, and the Web of Science Core Collection electronic databases. Studies were eligible for inclusion if they were peer-reviewed original research discussing the mechanism of indocyanine green retention in the results section in disease processes involving inflammation and/or necrosis, including cancer, and were available in English. Data were extracted using Covidence software.

Eighty-nine studies were included in the final analysis. Several features of indocyanine green retention were identified.

We identified several mechanistic features involved in indocyanine green accumulation in diseased tissue that overall had distinct mechanisms of indocyanine green retention in tumors, nontumor inflammation, and necrosis. Our study also reveals new insights on how inflammatory infiltrate influences indocyanine green fluorescence imaging. These findings are noteworthy because they add to our understanding of how fluorescence-guided surgery may be optimized based on the pathology of interest via specific indocyanine green dosing and timing of image acquisition.