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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 6

The effect of manual stimulation on lymphatic clearance in the ventral aspect of the torso of anesthetized pig 1 after bolus intradermal administration of 50 μl indocyanine green (0.0075 mg/ml) in a solution of Kolliphor HS15 (10 mg/ml) using MicronJet600 microneedles.

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The effect of manual stimulation on lymphatic clearance in the ventral a...
(A) Injection pattern, indicating labeling of the injection and massaged sites. (B) Measurements of the fluorescence signal with the use of the device. (C and D) Normalized fluorescence signal at each injection site over time in (C) nonmassaged and (D) massaged sites. (E) AUCs of ICG clearance curves from paired nonmassaged and massaged sites and comparison of sites 1 and 2 from the chest region. n represents the number of injection sites, and n = 4 for massaged and nonmassaged sites. Data were compared by paired Student’s t test; **P < 0.01. ICG, indocyanine green.

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