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?:abstract
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OBJECTIVE: Herein we used near-infrared fluorescence lymphatic imaging in a pilot study to assess lymphatics in pre-ulcerative (C2-C4) venous insufficiency and determine whether involvement and/or degradation of lymphatic anatomy or function could play a role in the progression of chronic venous insufficiency. We also explored the role of lymphatics in early peripheral arterial disease. METHODS: After informed consent and following intradermal injections of indocyanine green for rapid lymphatic uptake, near-infrared fluorescence lymphatic imaging was employed to assess lymphatic anatomical structure and quantify lymphatic propulsion rates in subjects with early venous insufficiency. Anatomical observations included interstitial backflow, characterized by the abnormal spreading of indocyanine green from the injection site primarily into the surrounding interstitial tissues; dermal backflow, characterized by the retrograde movement of dye-laden lymph from collecting lymphatics into the lymphatic capillaries; and lymphatic vessel segmentation and dilation. RESULTS: Ten venous insufficiency subjects were enrolled, resulting in three legs with C2 disease, eight legs with C3, eight legs with C4 disease, and one leg with C5 disease. Interstitial and/or dermal backflow were observed in 25%, 33%, and 41% of injection sites in each limb with C2, C3, and C4 disease, respectively. Distinct vessel segmentation and dilation was observed in limbs with C3 and higher classification, and dermal backflow proximal to the injection sites was observed in two legs with C4 disease and in the inguinal region of the C5 study subject. Overall average lymph propulsion rates were 1.3±0.4 contractile events/min, 1.2±0.7 events/min, and 0.8±0.5 events/min for limbs with C2, C3, and C4 disease respectively. One subject with peripheral arterial disease, who had previously undergone bypass surgery, presented with extensive dermal backflow and lymphatic reflux. CONCLUSIONS: Near-infrared fluorescence lymphatic imaging demonstrate that, compared to normal health subjects, lymphatic anatomy and contractile function generally degrade with severity of venous insufficiency. Lymphatic abnormalities mimic those in early cancer-acquired lymphedema subjects, as previously observed by us and others. Additional studies are needed to decipher the relationship, including any causality, between lymphatic dysfunction and peripheral vascular disease and venous insufficiency.
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