Development and optimization of near-infrared functional lymphatic imaging in health and lymphedema

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Weiler, Michael Joseph
Dixon, J. Brandon
Botchwey, Edward A.
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The lymphatic vasculature is present in nearly all tissues of the body and serves three primary functions: (1) regulation of tissue fluid homeostasis through the transport of large proteins and excess interstitial fluid, (2) immune cell trafficking, and (3) lipid transport. When the normal function of the lymphatic system deteriorates, many complications can arise. Loss of lymphatic pump function often leads to tissue fluid accumulation, fibrosis, and lipid deposition – a disease known as lymphedema. Despite the critical roles that it performs, very little is known about the lymphatic vasculature in comparison to the blood vasculature. One of the main reasons for this knowledge gap may be the lack of in vivo imaging techniques to non-invasively visualize and obtain quantifiable information regarding lymphatic function, both in health and disease. New techniques are needed to better study lymphatic biology, elucidate the functional role of lymphatics and lymphangiogenesis in health and disease conditions, and better diagnose patients with lymphatic disease at an early stage before any resulting tissue damage is permanent. Near-infrared (NIR) lymphatic imaging has emerged as a new technology for imaging of lymphatic architecture and quantification of vessel function. Although the technique has shown very exciting early results, the technique remains immature and several enhancements specifically for lymphatic imaging and functional quantification remain necessary. Therefore, we have characterized and optimized NIR imaging specifically for lymphatic vessels through a physical and physiological approach. Furthermore, the enhanced NIR lymphatic imaging technique was performed in the context of a novel rodent model of lymphedema to evaluate and characterize the role of lymphatic vessel function in the progression of the disease.
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