Abstract 4331: Assessment of cancer-related lymphatic impairment using NIR fluorescent imaging

Abstract

Abstract The lymphatic system contributes a major pathway for cancer metastasis and, through lymph node biopsy, provides the primary prognostic factor guiding therapy post-operative cancer patients. However, survivorship and quality of life for cancer survivors who undergo lymph node dissection can be complicated by lymphedema (LE). The etiology of LE is unknown and in this study, we developed methods to image lymphatic structure and function and its response to LE treatment to gain new understandings of the disease. Twenty unilateral LE and 24 normal control subjects were recruited in an IRB and FDA approved, Phase 0 exploratory trial. Onset of LE occurred after cancer treatment in 13 of the 20 LE subjects. Total dose of less than 400 µg of indocyanine green was injected intradermally in bilateral arms or legs. Immediately after the injections, a diffused excitation light illuminated the limbs and NIR fluorescence images were obtained using custom-built imaging systems. Twenty-two of the 44 subjects received the only accepted, but controversial therapy for LE, manual lymph drainage (MLD). Images were obtained immediately before and after MLD. Apparent lymph velocities and periods between lymphatic propulsion events were computed from fluorescence images. Images show dramatically different architecture of lymphatics between control normal and LE subjects. Well defined and organized lymphatic structures as well as active propulsions of lymph “packets” were commonly seen in normal limbs. In LE limbs, however, extravascular dye accumulation, networks of lymphatic capillaries, tortuous lymphatic vessels, and fewer propulsions were seen. The results without or before MLD show that the apparent velocity and periods between propulsions in average are 0.79 cm/s and 48.2 s for control arms and 0.94 cm/s and 52.2 s for control legs; 0.90 cm/s and 33.2 s for symptomatic arms and 0.78 cm/s and 72.1 s for symptomatic legs in LE subjects; 0.79 cm/s and 39.6 s for asymptomatic arms and 0.83 cm/s and 65.3 s for asymptomatic legs in LE subjects. In addition, an increase in velocity and a decrease in propulsion period were seen in the improvement of lymphatic function following MLD in subjects who received treatment. MLD resulted in increased apparent lymph velocities in the symptomatic (+23%) and asymptomatic (+25%) limbs of LE subjects and in the control limbs (+28%) of normal subjects. The lymphatic propulsion periods decreased in the symptomatic (−9%) and asymptomatic (−20%) limbs of LE subjects, and in the control limbs (−23%). NIR fluorescent imaging allows the in vivo visualization of the lymphatics architecture and quantification of lymphatic function. It could be used not only to study the impairment of lymphatic function after cancer surgery but also to direct treatment of LE subjects. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4331.