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Objective Assessment of Lymphatic Function via Serum Indocyanine Green Quantification
Xizhao Chen^*, Jung E. Baik, Jinyeon Shin, Gopika Ashokan, Annica Stull-Lane, Sarit Pal, Geoffrey Hespe, Babak J. Mehrara, Raghu Kataru
Surgery, Memorial Sloan Kettering Cancer Center, New York, NY

Background:
Lymphedema lacks a reliable, objective, and clinically scalable method for early diagnosis and treatment monitoring. Current approaches depend on delayed volume changes or qualitative imaging. We developed a rapid, quantitative assay of lymphatic function based on systemic uptake of intradermally injected indocyanine green (ICG).
Methods:
Serum ICG kinetics were analyzed following intradermal injection in multiple murine models reflecting clinically relevant lymphatic dysfunction, including genetic (VEGFR3 haploinsufficiency) (Figure a), inducible lymphatic ablation (Figure b), aging (Figure c), and surgical models (tail lymphedema and popliteal lymph node dissection) (Figures d and e). Structural and functional deficits were validated using immunofluorescence, near-infrared imaging, and dendritic cell migration assays. Serum tracer levels were quantified longitudinally and summarized by area under the curve (AUC).
Results:
Across all models, lymphatic dysfunction was characterized by reduced vessel density, impaired pumping, and diminished immune cell trafficking. These deficits were consistently mirrored by significantly decreased systemic ICG levels and AUC. Notably, serum ICG quantification detected lymphatic impairment in the absence of overt swelling, demonstrating sensitivity to early and subclinical disease. Findings were reproducible across alternative fluorescent tracers, supporting robustness and generalizability.
Conclusion:
Serum ICG quantification represents a novel, rapid, and clinically translatable biomarker of lymphatic function. By converting a widely used imaging agent into a quantitative systemic readout, this approach enables objective detection of early disease, longitudinal monitoring, and rigorous assessment of surgical and medical interventions. This platform has the potential to fundamentally shift how lymphedema is diagnosed, monitored, and managed.
Models adjusted for BMI, tissue expander size, and axillary irradiation. OR > 1 indicates higher odds with early exchange.

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