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 post-surgical 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 is non-invasively delivered to the dermal layer of the skin using MicronJet600TM hollow microneedles, and the fluorescence signal decay at the injection site is 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 new 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 non-invasive and quantitative clinical “office-test” for lymphatic function assessment.
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