Sensitivity analysis of near-infrared functional lymphatic imaging

Abstract

Abstract. Near-infrared imaging of lymphatic drainage of injected indocyanine green (ICG) has emerged as a new technology for clinical imaging of lymphatic architecture and quantification of vessel function, yet the imaging capabilities of this approach have yet to be quantitatively characterized. We seek to quantify its capabilities as a diagnostic tool for lymphatic disease. Imaging is performed in a tissue phantom for sensitivity analysis and in hairless rats for in vivo testing. To demonstrate the efficacy of this imaging approach to quantifying immediate functional changes in lymphatics, we investigate the effects of a topically applied nitric oxide (NO) donor glyceryl trinitrate ointment. Premixing ICG with albumin induces greater fluorescence intensity, with the ideal concentration being 150 μg∕mL ICG and 60 g∕L albumin. ICG fluorescence can be detected at a concentration of 150 μg∕mL as deep as 6 mm with our system, but spatial resolution deteriorates below 3 mm, skewing measurements of vessel geometry. NO treatment slows lymphatic transport, which is reflected in increased transport time, reduced packet frequency, reduced packet velocity, and reduced effective contraction length. NIR imaging may be an alternative to invasive procedures measuring lymphatic function in vivo in real time.

Mechanical forces and lymphatic transport

“…Recent innovations to study pump function of lymphatic vessels isolated from mice opens the door to a wide variety of transgenic and knockout models to expand our knowledge (Liao et al, 2011; Scallan and Davis, 2013). New techniques to non-invasively study lymphatic function in both animals and humans are also emerging and will aid with understanding human lymphedema (Aldrich et al, 2012; Maus et al, 2012; Nelson et al, 2014; Rasmussen et al, 2010; Tan et al, 2011; Weiler and Dixon, 2013; Weiler et al, 2012). These new approaches will help with the continued need to investigate the cellular and molecular mechanisms by which lymphatic vessels respond to mechanical cues to optimize lymph flow.…”

Demonstration of ATP-Dependent, Transcellular Transport of Lipid Across the Lymphatic Endothelium Using an In Vitro Model of the Lacteal

“…Although it is fairly well established that long-chain fatty acids are almost exclusively transported in lymph in the intestine even in the presence of blood capillaries, since the size of the molecules are too large to significantly penetrate the blood endothelial barrier (40). Indeed, near-infrared imaging data from our lab in other tissue beds has demonstrated that particles larger than a few nanometers are preferentially taken up by the lymphatics, not the vasculature (41,42). In vivo the presence of flow in the lacteal through open junctions would produce a convective force that favors paracellular transport.…”

Imaging the lymphatic system

“…Photons near the infrared range of the spectrum penetrate farther than those near the ultraviolet. Thus, with optics and detectors that operate in the near infrared, it is possible to obtain relatively high resolution images up to a few millimeters into soft tissues (Weiler et al, 2012). This requires fluorescent tracers that absorb and emit at near infrared wavelengths, generally in the 750–1000 nm range.…”