BACKGROUND: Although the importance of lymphatic function is well recognized, the lack of real-time imaging modalities limits our understanding of its role in many diseases. In a phase 0 exploratory study, we used dynamic, near-infrared (NIR) fluorescence imaging to assess the extremes of lymphatic architecture and transport in healthy human subjects and in subjects clinically diagnosed with unilateral lymphedema (LE), a disease that can be prevalent in cancer survivors. METHODS AND RESULTS: Active lymphatic propulsion was imaged after intradermal injections of 25 µg of indocyanine green (total maximum dose ≤400 µg) bilaterally in the arms or legs of control and subjects. Images show well-defined lymphatic structures with propulsive dye transport in limbs of healthy subjects. In LE subjects, we observed extravascular dye accumulation, networks of fluorescent lymphatic capillaries, and/or tortuous lymphatic vessels in all symptomatic and some asymptomatic limbs. Statistical models indicate that disease status and/or limb significantly affect parameters of apparent lymph propagation velocity and contractile frequency. CONCLUSIONS: These clinical research studies demonstrate the potential of NIR fluorescence imaging as a diagnostic measure of functional lymphatics and as a new tool in translational research studies to decipher the role of the lymphatic system in cancer and other diseases.
BACKGROUND: Although the importance of lymphatic function is well recognized, the lack of real-time imaging modalities limits our understanding of its role in many diseases. In a phase 0 exploratory study, we used dynamic, near-infrared (NIR) fluorescence imaging to assess the extremes of lymphatic architecture and transport in healthy human subjects and in subjects clinically diagnosed with unilateral lymphedema (LE), a disease that can be prevalent in cancer survivors. METHODS AND RESULTS: Active lymphatic propulsion was imaged after intradermal injections of 25 µg of indocyanine green (total maximum dose ≤400 µg) bilaterally in the arms or legs of control and subjects. Images show well-defined lymphatic structures with propulsive dye transport in limbs of healthy subjects. In LE subjects, we observed extravascular dye accumulation, networks of fluorescent lymphatic capillaries, and/or tortuous lymphatic vessels in all symptomatic and some asymptomatic limbs. Statistical models indicate that disease status and/or limb significantly affect parameters of apparent lymph propagation velocity and contractile frequency. CONCLUSIONS: These clinical research studies demonstrate the potential of NIR fluorescence imaging as a diagnostic measure of functional lymphatics and as a new tool in translational research studies to decipher the role of the lymphatic system in cancer and other diseases.
Authors: M J Karkkainen; A Saaristo; L Jussila; K A Karila; E C Lawrence; K Pajusola; H Bueler; A Eichmann; R Kauppinen; M I Kettunen; S Yla-Herttuala; D N Finegold; R E Ferrell; K Alitalo Journal: Proc Natl Acad Sci U S A Date: 2001-10-09 Impact factor: 11.205
Authors: J Fang; S L Dagenais; R P Erickson; M F Arlt; M W Glynn; J L Gorski; L H Seaver; T W Glover Journal: Am J Hum Genet Date: 2000-11-08 Impact factor: 11.025
Authors: N Unno; M Nishiyama; M Suzuki; N Yamamoto; K Inuzuka; D Sagara; H Tanaka; H Konno Journal: Eur J Vasc Endovasc Surg Date: 2008-06-04 Impact factor: 7.069
Authors: G Brice; S Mansour; R Bell; J R O Collin; A H Child; A F Brady; M Sarfarazi; K G Burnand; S Jeffery; P Mortimer; V A Murday Journal: J Med Genet Date: 2002-07 Impact factor: 6.318
Authors: Alexander L Vahrmeijer; Merlijn Hutteman; Joost R van der Vorst; Cornelis J H van de Velde; John V Frangioni Journal: Nat Rev Clin Oncol Date: 2013-07-23 Impact factor: 66.675
Authors: Patricia E Burrows; Manuel L Gonzalez-Garay; John C Rasmussen; Melissa B Aldrich; Renie Guilliod; Erik A Maus; Caroline E Fife; Sunkuk Kwon; Philip E Lapinski; Philip D King; Eva M Sevick-Muraca Journal: Proc Natl Acad Sci U S A Date: 2013-05-06 Impact factor: 11.205
Authors: John C Rasmussen; Karen L Herbst; Melissa B Aldrich; Chinmay D Darne; I-Chih Tan; Banghe Zhu; Renie Guilliod; Caroline E Fife; Erik A Maus; Eva M Sevick-Muraca Journal: Obesity (Silver Spring) Date: 2014-07-09 Impact factor: 5.002
Authors: Jason C Gardenier; Geoffrey E Hespe; Raghu P Kataru; Ira L Savetsky; Jeremy S Torrisi; Gabriela D García Nores; Joseph J Dayan; David Chang; Jamie Zampell; Inés Martínez-Corral; Sagrario Ortega; Babak J Mehrara Journal: JCI Insight Date: 2016-09-22
Authors: Holly A Robinson; SunKuk Kwon; Mary A Hall; John C Rasmussen; Melissa B Aldrich; Eva M Sevick-Muraca Journal: J Vis Exp Date: 2013-03-08 Impact factor: 1.355