Abstract

We demonstrate the ability to non-invasively and quantitatively image lymphatic architecture and contractile function using dynamic near-infrared (NIR) fluorescence imaging with injection of indocyanine green in normal and transgenic mice. Unlike normal mice, which showed well defined lymphatic drainage patterns and orthograde propagation of contraction waves, we observed tortuous and mispatterned lymphatic vessels and persistent retrograde lymph flow in mice with deficiency in Prox1, a transcription factor essential for lymphatic vascular development. NIR fluorescence imaging provides a method for quantifying lymphatic function for future studies designed to discern differences in lymphatic function in murine models of human lymphatic disease.

Highlights

  • The lymphatic system plays an important yet poorly understood role in cancer metastasis, immune surveillance, lipid absorption, and fluid homeostasis

  • In mouse models of human disease, lymphatic architecture and function has been examined using traditional imaging techniques with injection of Evans blue dye (EBD) or dextran bound with common fluorescent dyes that excite in the visible wavelength range [4,5,6]

  • The physiological and pathophysiological importance of the lymphatic system could be characterized with non-invasive dynamic NIR fluorescence imaging

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Summary

Introduction

The lymphatic system plays an important yet poorly understood role in cancer metastasis, immune surveillance, lipid absorption, and fluid homeostasis. In mouse models of human disease, lymphatic architecture and function has been examined using traditional imaging techniques with injection of Evans blue dye (EBD) or dextran bound with common fluorescent dyes that excite in the visible wavelength range [4,5,6]. All of these studies either employed an invasive, acute preparation that can impact lymphatic function or non-invasive imaging of the lymphatics in the ear or tail where visual observations can be directly made. Lymphatic function and architecture is currently imaged with lymphoscintigraphy, a nuclear imaging technique which lacks the temporal and spatial resolution required to assess dynamic, lymphatic contractile function

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