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Current diagnostic methods for evaluating the functionality of the lymphatic vascular system usually do not provide quantitative data and suffer from many limitations including high costs, complexity, and the need to perform them in hospital settings. In this work, we present a quantitative, simple outpatient technology named LymphMonitor to quantitatively assess lymphatic function. This method is based on the painless injection of the lymphatic-specific near-infrared fluorescent tracer indocyanine green complexed with human serum albumin, using MicronJet600TM microneedles, and monitoring the disappearance of the fluorescence signal at the injection site over time using a portable detection device named LymphMeter. This technology was investigated in 10 patients with unilateral leg or arm lymphedema. After injection of a tracer solution into each limb, the signal was measured over 3 h and the area under the normalized clearance curve was calculated to quantify the lymphatic function. A statistically significant difference in lymphatic clearance in the healthy versus the lymphedema extremities was found, based on the obtained area under curves of the normalized clearance curves. This study provides the first evidence that the LymphMonitor technology has the potential to diagnose and monitor the lymphatic function in patients.
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The quantitative assessment of lymphatic dermal clearance using NIR fluorescent tracers is particularly important for the early diagnosis of several potential disabling diseases. Currently, half-life values are computed using a mono-exponential mathematical model, neglecting diffusion of the tracer within the dermis after injection. The size and position of the region of interest are subjectively manually selected around the point of injection on the skin surface where the fluorescence signal intensity is averaged, neglecting any spatial information contained in the image. In this study we present and test a novel mathematical model allowing the objective quantification of dermal clearance, taking into consideration potential dermal diffusion. With only two parameters, this "clearance-diffusion" model is simple enough to be applied in a variety of settings and requires almost no prior information about the system. We demonstrate that if dermal diffusion is low, the mono-exponential approach is suitable but still lacking objectivity. However, if dermal diffusion is substantial, the clearance-diffusion model is superior and allows the accurate calculation of half-life values.
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Enhancing our understanding of lymphatic anatomy from the microscopic to the anatomical scale is essential to discern how the structure and function of the lymphatic system interacts with different tissues and organs within the body and contributes to health and disease. The knowledge of molecular aspects of the lymphatic network is fundamental to understand the mechanisms of disease progression and prevention. Recent advances in mapping components of the lymphatic system using state of the art single cell technologies, the identification of novel biomarkers, new clinical imaging efforts, and computational tools which attempt to identify connections between these diverse technologies hold the potential to catalyze new strategies to address lymphatic diseases such as lymphedema and lipedema. This manuscript summarizes current knowledge of the lymphatic system and identifies prevailing challenges and opportunities to advance the field of lymphatic research as discussed by the experts in the workshop.
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- Lipedema (1)
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