title: A novel method of measuring human lymphatic pumping using indocyanine green fluorescence lymphography.
abstract: OBJECTIVE
  Lymph transportation through the body is partly controlled by the intrinsic pumping of lymphatic vessels. Although an understanding of this process is important for medical application, little is currently known because it is difficult to measure. Here, we introduce an easy, safe, and cost-effective technique for measuring lymphatic pumping in leg superficial lymphatic vessels. Readings obtained with this technique were compared with values obtained with dynamic lymphoscintigraphy. Differences in lymphatic pumping between healthy volunteers and patients with lymphedema were also investigated.
  
  
  METHODS
  Indocyanine green (ICG) fluorescence lymphography was performed by subcutaneously injecting 0.3 mL of ICG (0.5%) into the dorsum of the foot. Real-time fluorescence images of lymph propulsion were obtained with an infrared-light camera system with the individual supine or sitting. A custom-made transparent sphygmomanometer cuff was wrapped around the lower leg and connected to a standard mercury sphygmomanometer. The cuff was inflated to 60 mm Hg and then gradually deflated at 5-minute intervals to lower the pressure by 10-mm Hg steps until the fluorescence contrast agent exceeded the upper border of the cuff, indicating that the lymphatic contraction had overcome the cuff pressure. Lymph pumping pressure (P(pump)) was defined as the value of the cuff pressure when the contrast agent exceeded the upper border of the cuff. We measured P(pump) among healthy volunteers who maintained a supine position and compared these values with measurements obtained from lymphoscintigraphy. P(pump) values while sitting were also compared between 30 legs from healthy volunteers and 30 legs from lymphedematous patients.
  
  
  RESULTS
  Among healthy, supine participants, P(pump) was 25.2 ± 16.7 mm Hg (mean ± standard deviation [SD]) when measured by ICG fluorescence lymphography. These values were significantly correlated with values taken using dynamic lymphoscintigraphy (r(2) = 0.54, p < .01), while 2 SDs of the mean were approximately 20 mm Hg, suggesting a substantial disagreement between the two methods (Bland-Altman plots). In the comparison of seated measurements, readings for healthy participants (P(pump) = 29.3 ± 16.0) were higher than those for lymphedematous participants (13.2 ± 14.9).
  
  
  CONCLUSIONS
  ICG fluorescence is an accurate-as well as a safe, easy, and economical-method of measuring lymphatic pumping. Therefore, it may develop as a vital tool for diagnosing lymphatic malfunctions even when they are only in their formative stages. Studies that use this technique may increase our knowledge of the lymphatic system as a whole, allowing us to develop better treatments for lymphatic disorders.
authors.affiliation: Division of Vascular Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan. unno@hama-med.ac.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Unno
authors.forename: Motohiro
authors.initials: M
authors.lastname: Nishiyama
authors.forename: Minoru
authors.initials: M
authors.lastname: Suzuki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sagara
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Mano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konno
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage; D006801:Humans; D007208:Indocyanine Green / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D007564:Japan; D035002:Lower Extremity; D042601:Lymphatic Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008209:Lymphedema / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000503:physiopathology; D008220:Lymphography / Q000379:methods*; D008297:Male; D008875:Middle Aged; D056888:Patient Positioning; D011237:Predictive Value of Tests; D011312:Pressure; D011877:Radionuclide Imaging; D019722:Sphygmomanometers; D016683:Supine Position
chemical_list: D005456:Fluorescent Dyes; D007208:Indocyanine Green