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Quantitative measurement of lymphatic function in mice by noninvasive near-infrared imaging of a peripheral vein
Steven T. Proulx, … , Jean-Christophe Leroux, Michael Detmar
Steven T. Proulx, … , Jean-Christophe Leroux, Michael Detmar
Published January 12, 2017
Citation Information: JCI Insight. 2017;2(1):e90861. https://doi.org/10.1172/jci.insight.90861.
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Resource and Technical Advance Vascular biology

Quantitative measurement of lymphatic function in mice by noninvasive near-infrared imaging of a peripheral vein

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Abstract

Optical imaging methods have been developed to measure lymphatic function in skin; however, the lymphatic system of many organs is not accessible to this technology. Since lymphatic transport of macromolecules from any organ proceeds to the blood circulation, we aimed to develop a method that can measure lymphatic function by monitoring the fluorescence in a superficial vein of an interstitially injected tracer. We selected a 40-kDa PEGylated near-infrared dye conjugate, as it showed lymphatic system–specific uptake and extended circulation in blood. Lymphatic transport to blood from subcutaneous tissue required a transit time before signal enhancement was seen in blood followed by a steady rise in signal over time. Increased lymphatic transport was apparent in awake mice compared with those under continuous anesthesia. The methods were validated in K14-VEGFR-3-Fc and K14-VEGF-C transgenic mice with loss and gain of lymphatic function, respectively. Reduced lymphatic transport to blood was also found in aged mice. The technique was also able to measure lymphatic transport from the peritoneal cavity, a location not suitable for optical imaging. The method is a promising, simple approach for assessment of lymphatic function and for monitoring of therapeutic regimens in mouse models of disease and may have potential for clinical translation.

Authors

Steven T. Proulx, Qiaoli Ma, Diana Andina, Jean-Christophe Leroux, Michael Detmar

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Figure 2

Determination of tracer fluorescent signal kinetics and sensitivity of detection in blood.

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Determination of tracer fluorescent signal kinetics and sensitivity of d...
(A) Monitoring of saphenous vein signals after tail vein injections of 20-kDa PEG–IRDye800 conjugate (P20D800) or 40-kDa PEG–IRDye800 conjugate (P40D800) (25 μl of 40 μM each). n = 4 mice each tracer. (B) Schematic showing stepwise tail vein infusion setup to determine sensitivity of detection in blood of P40D800 tracer. (C) Plot showing saphenous vein signal enhancement during stepwise infusions of 10 μl of 1 μM P40D800. Representative of n = 3 independent experiments. (D) Plot showing saphenous vein signal during stepwise infusions of 10 μl of 0.1 μM P40D800. Representative of n = 4 independent experiments. Detection threshold indicates time point where signal increase is first detected after 3 infusions of 0.1 μM P40D800.

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