title: In vivo visualization and quantification of collecting lymphatic vessel contractility using near-infrared imaging.
abstract: Techniques to image lymphatic vessel function in either animal models or in the clinic are limited. In particular, imaging methods that can provide robust outcome measures for collecting lymphatic vessel function are sorely needed. In this study, we aimed to develop a method to visualize and quantify collecting lymphatic vessel function in mice, and to establish an in vivo system for evaluation of contractile agonists and antagonists using near-infrared fluorescence imaging. The flank collecting lymphatic vessel in mice was exposed using a surgical technique and a near-infrared tracer was infused into the inguinal lymph node. Collecting lymphatic vessel contractility and valve function could be easily visualized after the infusion. A diameter tracking method was established and the diameter of the vessel was found to closely correlate to near-infrared fluorescence signal. Phasic contractility measures of frequency and amplitude were established using an automated algorithm. The methods were validated by tracking the vessel response to topical application of a contractile agonist, prostaglandin F2α, and by demonstrating the potential of the technique for non-invasive evaluation of modifiers of lymphatic function. These new methods will enable high-resolution imaging and quantification of collecting lymphatic vessel function in animal models and may have future clinical applications.
authors.affiliation: Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Chloé
authors.initials: C
authors.lastname: Chong
authors.affiliation: Biomedical Optics Research Laboratory (BORL), Department of Neonatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
authors.forename: Felix
authors.initials: F
authors.lastname: Scholkmann
authors.affiliation: Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Samia B
authors.initials: SB
authors.lastname: Bachmann
authors.affiliation: Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Paola
authors.initials: P
authors.lastname: Luciani
authors.affiliation: Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Leroux
authors.affiliation: Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Detmar
authors.affiliation: Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Steven T
authors.initials: ST
authors.lastname: Proulx
mesh_terms: D000818:Animals; D015237:Dinoprost / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D008198:Lymph Nodes / Q000000981:diagnostic imaging* / Q000473:pathology; D042601:Lymphatic Vessels / Q000000981:diagnostic imaging* / Q000473:pathology; D051379:Mice; D061848:Optical Imaging / Q000379:methods*
chemical_list: D015237:Dinoprost