Long‐term effects of indocyanine green on lymphatic pump function

Introduction Near‐infrared (NIR) imaging with indocyanine green (ICG) has emerged as a potential technique for diagnosing lymphatic diseases, however, the long‐term effects of ICG on lymphatic function have not been studied in vivo. Therefore, we quantified the retention rate of ICG in lymphatic vessels and the effect of repeated ICG injections on lymphatic pump function. Methods Rats were given intradermal ICG injections and subsequently imaged using NIR to quantify lymphatic function as members of one of four treatment groups: (i) initial ICG injection with no follow‐up injection, (2) follow‐up ICG injection after 1 week, (3) 2 week follow‐up ICG injection, and (4) 1 month follow‐up ICG injection. Results and Conclusions ICG remained visible in rat collecting lymphatics for approximately two weeks, and NIR lymphatic function measurements after follow‐up ICG injections of 1 and 2 weeks showed significant reductions in fluid velocity, pulsatile flow frequency and clearance rate while no significant differences were observed after 1 month follow‐up ICG injections. These results indicate that ICG is retained in the local tissue space for an extended period and may suggest that lymphatic function is reduced during this time. ICG‐based NIR imaging diagnostics for lymphatic function, therefore, may necessitate a minimum of 1 month between subsequent ICG injections to avoid erroneous measurements of function.