Imaging the role of lymphatics in chronic inflammatory diseases
July 23-26, 2017
There is strong evidence that chronic inflammation contributes to a number conditions prevalent with aging, including peripheral vascular disease, rheumatoid arthritis, as well as Alzheimer’s disease. Yet despite being responsible for mediating immune responses, the lymphatic vasculature has largely escaped attention of biomedical engineers, research scientists, pharmaceutical companies, and health care professionals. The reason for this may be because the lymphatics are difficult to directly visualize in tissues. Interstitial fluid, immune cells, and foreign particles form colorless “lymph” when entering the lymphatics through the initial lymphatics that are located under the epidermis and line all the major organs of the body. From there the lymph is transited through the collecting and conducting vessels, the latter of which consist of a series of “lymph hearts” or lymphangions that propel lymph through the main thoracic duct before emptying into the supraclavicular vein (Fig 1). Conventional lymphatic imaging employs the administration of contrast agents for visualizing the lymphatics and lymph nodes using intradermal administration of radiocolloid for lymphoscintigraphy, or using surgical procedures to inject gadolinium or iodinated contrast agents for magnetic resonance or CT imaging. These techniques are not routinely used and none are suitable for imaging the lymphatics in a mouse or rat, the predominant animal models used in discovery research. Beginning in 2005, we began imaging the dynamic activity of the lymphatics in humans following intradermal injection of indocyanine green, illumination of tissues with 1.9 mW/cm2 of 785 nm near- infrared (NIR) light, and collection of the dim 830 nm NIR fluorescent (NIRF) light using a InGaAs Gen III intensifier coupled conventional CCD or sCMOS detector. Shortly thereafter, we began imaging lymphatic activity in animal models of human disease. Because of the sensitivity of the fluorescence technique, images can be acquired in 50 -200 ms to non-invasively visualize the dynamic lymphangion activity in vessels as deep as 3-4 centimeters for the first time in human adults. As a result of the rapid, “point-of-care” imaging offered by NIRF, we are able to image infants and children without the need for sedation (Greives, et al., Pediatrics, 2017)
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Eva Sevick-Muraca, "Imaging the role of lymphatics in chronic inflammatory diseases" in "Advances in Optics for Biotechnology, Medicine and Surgery XV", Peter So, Massachusetts Institute of Technology, USA Kate Bechtel, Triple Ring Technologies, USA Ivo Vellekoop, University of Twente, The Netherlands Michael Choma, Yale University, USA Eds, ECI Symposium Series, (2017). http://dc.engconfintl.org/biotech_med_xv/25