Function of Upper Extremity Human Lymphatics Assessed by Near-Infrared Fluorescence Imaging

Benjamin Kelly, BSc,1,2 Sheyanth Mohanakumar, MD, PhD,1 Niklas Telinius, MD, PhD,3 Mathias Alstrup, BSc,1,2 and Vibeke Hjortdal, MD, PhD, DMSc2. Lymphatic Research Biology 2019.


Background: Knowledge of functional parameters that can be used for evaluation of upper extremity lymphatic function is limited. This study aims to evaluate near-infrared fluorescence (NIRF) imaging for evaluation of lymphatic function in the human arm.

Methods and Results: Ten healthy male volunteers (age 25.7–1.3 years) were included and examined at two occasions. The lymphatic functional frequency and velocity were examined at baseline, during hyperthermia and after exercise. In addition, the maximum pressure generated by contraction of the lymphatic vessels was estimated. The mean contraction frequency was found to be 0.9–0.4/min, and the mean velocity of the propulsions was 1.1–0.3cm/s. The average maximal pressure generated by the contraction of the lymphatic vessels was 59–12mmHg. No significant difference in frequency, velocity, or pumping pressure was found between the two visits (p>0.05). Local hyperthermia increased contraction frequency significantly, whereas exercise decreased frequency and increased propulsion velocity.

Conclusions: The functional lymphatic parameters evaluated by NIRF imaging showed good repeatability with no significant difference between visits. Future examinations should be conducted with standardization of temperature and exercise, as these parameters were shown to alter lymphatic function

Main findings

  • 10 healthy subjects
  • All participants received a total of six intradermal ICG injections, covering three injections on each arm. Injections were given dorsally between the second and third and between the fourth and fifth proximal phalanges, and palmarly on the central part of the wrist.
  • All subjects underwent an identical 5-hour protocol, with a 2-week interval between examinations. The two appointments were scheduled at the same time of day to eliminate any diurnal changes. All sequences were recorded of the same segment of lymphatic vasculature to increase comparability.
  • Parameters included:
    • The average velocity of lymphatic propulsions. Change in velocity over time.
    • Pumping pressure. A minimum of two propulsions within 10 minutes was mandatory for confirmation.
    • The impact of exercise
    • The impact of hyperthermia
  • On average,3.7–1.4 lymphatic vessels were analyzed on each arm, the density of vessels ranging from 2 to 7 per arm. The anatomy of these superficial lymphatic vessels was found to be diverse and with great interindividual variation concerning the number of vessels and the course of these.
  • Functionally, the lymphatic vessels contracted with an average frequency of 0.9–0.4/min at baseline, and the packages traveled with an average velocity of 1.1–0.3cm/s. The average frequency was 0.9–0.4/min at the first visit and 0.9–0.4/min at the second visit. The average velocity was 1.1–0.3cm/s at the first visit and 1.0–0.3cm/s at the second visit. There was no significant difference between the frequency and the velocity at the two visits p>0.05.
  • There was no difference in the frequency at 40 and 80 minutes after injection, the frequency being 0.9–0.4/min and 0.8–0.4/min, respectively. However, after 150 minutes, the frequency significantly decreased by *30% to 0.6–0.4/min, p<0.05. This decrease persisted through to the last estimation at 180 minutes, 0.6–0.3/min. The velocity of the lymphatic packages was unaltered throughout the entire protocol.
  • After 2 minutes of handgrip exercise, the frequency significantly decreased from 1.1–0.3/min to 0.9–0.4/min, p<0.05. Contrarily the velocity of the lymphatic packages significantly increased after exercise.
  • After 5 minutes placement in 40 degrees C water, the hyperthermia of the lower arm significantly increased the frequency of the lymphatic vessels from 1.1–0.3/min to 1.5–0.5/min, p<0.05; however, the velocity of the lymphatic packages stayed unaltered.
  • The 2-week interval between sequences did not markedly affect the vessels visualized.
  • When looking at the frequency at 40, 80, 150, and 180 minutes after injection, there was a significant drop in frequency at 150 and 180 minutes after injection compared with 40 and 80 minutes after.