Non-invasive imaging of lymphatic remodeling in response to injury through photodynamic therapy

Abstract

The lymphatic system is an essential but often understudied in comparison with its cardiovascular counterpart. Such disparity could often be explained by the lack or complexity of the existing imaging and analysis techniques available for the quantification of lymphatics compared to the ones available for the blood vasculature. An additional challenge is the absence of representative in vivo models that efficiently replicate the lymphatic dysfunction observed in humans. Those factors motivate the continuous investigation of novel models for lymphatic diseases and ways to evaluate the overall function of the lymphatic system. Recently, it has been shown that verteporfin, a photosensitive drug widely used for photodynamic therapy (PDT) to ablate the blood vessels, provides a similar effect on lymphatic vessels. Here, we seek to administer verteporfin and perform PDT of collecting lymphatics in the mouse tail, which is a commonly used location for the study of lymphatic disorders and examine lymphatic remodeling, contractility, and transport in response to the procedure. To quantify the induced changes, the lymphatic function was evaluated using a near-infrared (NIR) imaging system. Additional image processing has been introduced to access the NIR tracer distribution following the lymphatic injury caused by the verteporfin administration. As a result, we are able to increase lymphatic permeability noninvasively at the targeted area. This technique has the potential to be a stand-alone procedure to investigate the lymphatic response to a localized leakage and reactive oxygen species (ROS) and serve as an improvement to existing in vivo models of lymphatic disorders.