Indocyanine Green and Lymphatic Imaging: Current Problems

Abstract

Background: Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has recently been presented as a comparatively easy and informative technique to image lymphatic channels in vivo. However, no data or references have been provided concerning the impact of ICG application on normal lymphatic contractility and lymph transport. Thus, the imaging agent and/or the method of administration may introduce a significant artifact. Methods and Results: Standard pharmacological tests were performed to investigate the influence of ICG on the spontaneous contractility of isolated, cannulated, and pressurized rat mesenteric lymphatic vessels. The data demonstrate that non-irradiated ICG dramatically and dynamically influences the contractility of rat lymphatic vessels in both a dose-and diluent-dependent manner with low ICG concentrations principally altering contractile frequency and higher ICG concentrations completely blocking lymphatic contractility. Conclusions: Currently, both researchers and doctors should exercise caution in extrapolating the data obtained with ICG imaging to normal lymphatic function regardless of whether it was obtained in mice, pigs, or humans. Careful and extended pharmacological tests must be performed to evaluate the mechanism of action of ICG on the contractility and physiology of lymphatic vessels with consideration of dose, diluent, and duration of irradiation.

Concentration of Indocyanine Green Does Not Significantly Influence Lymphatic Function as Assessed by Near-Infrared Imaging

“…It is likely that the published results by another group 17 showing changes in lymphatic function with varying ICG concentrations could be attributed to the use of very different experimental conditions than ours. The other group perfused ICG through ex vivo isolated mesenteric rat vessels at a fixed pressure and an imposed flow, while our studies noninvasively measured murine in vivo peripheral, inguinal-to-axillary postnodal efferent transport.…”

“…In our studies using a mouse model that simulates our human studies, ICG concentration, as well as the use of other NIR fluorophores, did not affect lymphatic function. Using this NIR technique developed in our laboratories, we have shown its use to direct therapy 17 as well as to detect improvement in lymphatic function immediately after therapy. 6,8 Noninvasive methods to investigate the lymphatic system can provide new avenues to discovery, diagnosis, and emerging therapies of lymphatic disorders and diseases.…”

Biological Basis of Therapeutic Lymphangiogenesis

“…Additional concerns were raised by the possibility that indocyanine green dye injection stimulates lymphatic smooth muscle contractions. 153 Nevertheless, nearinfrared imaging will likely soon allow better functional characterization of the various forms of lymphedema and more precise mapping of sentinel lymph nodes. Immunopositron emission tomography with radioactively labeled antibodies against LEC surface antigens such as LYVE-1 enables early visualization of tumor-and lymph nodeassociated lymphangiogenesis.…”

Lymphatic function measurements influenced by contrast agent volume and body position

“…Several studies have sought to characterize how some experimental parameters affect lymphatic functional measurements. These include studies that explored the effect of tracer type and size (13), ICG concentration (22), and whether the fluorophore, time after injection, and vessel selection alter the measurements (23). However, these studies did not compare different measurement techniques.…”