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Minimally invasive method for the point-of-care quantification of lymphatic vessel function
Anna K. Polomska, … , Jean-Christophe Leroux, Michael Detmar
Anna K. Polomska, … , Jean-Christophe Leroux, Michael Detmar
Published January 22, 2019
Citation Information: JCI Insight. 2019;4(4):e126515. https://doi.org/10.1172/jci.insight.126515.
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Resource and Technical Advance Dermatology Vascular biology

Minimally invasive method for the point-of-care quantification of lymphatic vessel function

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Abstract

Current clinical methods for the evaluation of lymphatic vessel function, crucial for early diagnosis and evaluation of treatment response of several pathological conditions, in particular of postsurgical lymphedema, are based on complex and mainly qualitative imaging techniques. To address this unmet medical need, we established a simple strategy for the painless and quantitative assessment of cutaneous lymphatic function. We prepared a lymphatic-specific tracer formulation, consisting of the clinically approved near-infrared fluorescent dye, indocyanine green, and the solubilizing surfactant Kolliphor HS15. The tracer was noninvasively delivered to the dermal layer of the skin using MicronJet600 hollow microneedles, and the fluorescence signal decay at the injection site was measured over time using a custom-made, portable detection device. The decay rate of fluorescence signal in the skin was used as a direct measure of lymphatic vessel drainage function. With this method, we could quantify impaired lymphatic clearance in transgenic mice lacking dermal lymphatics and distinguish distinct lymphatic clearance patterns in pigs in different body locations and under manual stimulus. Overall, this method has the potential for becoming a noninvasive and quantitative clinical “office test” for lymphatic function assessment.

Authors

Anna K. Polomska, Steven T. Proulx, Davide Brambilla, Daniel Fehr, Mathias Bonmarin, Simon Brändli, Mirko Meboldt, Christian Steuer, Tsvetina Vasileva, Nils Reinke, Jean-Christophe Leroux, Michael Detmar

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Figure 1

Influence of Kolliphor HS15 on spectroscopic properties of indocyanine green.

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Influence of Kolliphor HS15 on spectroscopic properties of indocyanine g...
If not otherwise stated, concentrations of indocyanine green (ICG) and Kolliphor HS15 were 0.0075 mg/ml and 10 mg/ml, respectively. (A) Fluorescence intensity of ICG at different concentrations in water or in Kolliphor HS15 solutions at 5, 10, and 20 mg/ml. (B) Fluorescence intensity of ICG in a solution containing Kolliphor HS15 at different concentrations. In A and B, fluorescence intensity is shown at 808 nm and 826 nm for ICG-water and ICG-Kolliphor HS15, respectively. (C and D) Influence of different amounts of HSA on spectroscopic properties of ICG-water and ICG-Kolliphor HS15. (C) Fluorescence intensity and (D) emission maximum of ICG-water and ICG-Kolliphor HS15 after mixing with HSA. Fluorescence intensity shown at 820 nm and 826 nm for ICG-water-HSA and for ICG-Kolliphor HS15, respectively. (E and F) Stability of ICG-water and in ICG-Kolliphor HS15. (E) Fluorescence intensity of the solutions measured over 140 days. Error bars are smaller than the symbols and not visible. (F) Fluorescence intensity of respective solutions measured over 24 hours in absence and in presence of 5 mM H2O2. In E and F, fluorescence intensity is shown at 808 nm and 826 nm for ICG-water and for ICG-Kolliphor HS15, respectively. Data presented in A–D and F were obtained in n = 3 individual experiments. Data in E were obtained in 1 experiment with 3 individual samples. All data are shown as mean ± SD.

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