Chong Chloé, Scholkmann Felix, Bachmann Samia B, Luciani Paola, Leroux Jean-Christophe, Detmar Michael, Proulx Steven T
Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, 8093 Zurich, Switzerland.
Biomedical Optics Research Laboratory (BORL), Department of Neonatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
Sci Rep. 2016 Mar 10;6:22930. doi: 10.1038/srep22930.
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.
在动物模型或临床中用于成像淋巴管功能的技术有限。特别是,迫切需要能够为收集淋巴管功能提供可靠结果指标的成像方法。在本研究中,我们旨在开发一种方法来可视化和量化小鼠收集淋巴管的功能,并建立一个使用近红外荧光成像评估收缩性激动剂和拮抗剂的体内系统。采用手术技术暴露小鼠胁腹的收集淋巴管,并将近红外示踪剂注入腹股沟淋巴结。注入后,收集淋巴管的收缩性和瓣膜功能很容易可视化。建立了一种直径跟踪方法,发现血管直径与近红外荧光信号密切相关。使用自动算法建立了频率和幅度的阶段性收缩性测量方法。通过跟踪血管对局部应用收缩性激动剂前列腺素F2α的反应,并证明该技术用于无创评估淋巴管功能调节剂的潜力,对这些方法进行了验证。这些新方法将能够对动物模型中的收集淋巴管功能进行高分辨率成像和量化,并可能在未来应用于临床。