Serum indocyanine green quantification enables objective assessment of lymphatic function

Secondary lymphedema is characterized by impaired lymphatic drainage, yet current diagnostic approaches rely on limb volume measurements and qualitative measures of lymphatic function. In this study, we tested the hypothesis that systemic uptake following intradermal injection of fluorescent tracers can serve as a quantitative biomarker of lymphatic transport. Using various preclinical models of lymphatic dysfunction, including genetic VEGFR3 haploinsufficiency, inducible lymphatic endothelial cell depletion, aging, and surgical lymphatic injury, we show that decreased serum concentrations of intradermally administered indocyanine green (ICG) correlate with indicators of impaired lymphatic function, including reduced lymphatic vessel density, diminished lymphatic pumping, and impaired dendritic cell migration. Together, these findings suggest that quantification of the serum concentrations of peripherally injected dyes selectively transported by the lymphatic system may be a useful means of assessing lymphatic function.