Near-Infrared Fluorescence Imaging in Humans with Indocyanine Green: A Review and Update~!2009-12-07~!2009-12-23~!2010-05-26~!

Abstract

Near-infrared (NIR) fluorescence imaging clinical studies have been reported in the literature with six different devices that employ various doses of indocyanine green (ICG) as a non-specific contrast agent. To date, clinical applications range from (i) angiography, intraoperative assessment of vessel patency, and tumor/metastasis delineation following intravenous administration of ICG, and (ii) imaging lymphatic architecture and function following subcutaneous and intradermal ICG administration. In the latter case, NIR fluorescence imaging may enable new discoveries associated with lymphatic function due to (i) a unique niche that is not met by any other conventional imaging technology and (ii) its exquisite sensitivity enabling high spatial and temporal resolution. Herein, we (i) review the basics of clinical NIR fluorescence imaging, (ii) survey the literature on clinical application of investigational devices using ICG fluorescent contrast, (iii) provide an update of non-invasive dynamic lymphatic imaging conducted with our FDPM device, and finally, (iv) comment on the future NIR fluorescence imaging for non-invasive and intraoperative use given recent demonstrations showing capabilities for imaging following microdose administration of contrast agent.

Noninvasive positron emission tomography and fluorescence imaging of CD133 + tumor stem cells

“…PET and NIR fluorescence imaging are sensitive imaging modalities that are becoming increasingly important in clinical practice (27,30,(39)(40)(41). We show here that particularly 64 Cu-NOTA-AC133 mAb-mediated microPET yields high-quality, highresolution images with outstanding tumor-to-background contrast.…”

Photoacoustic imaging of lymphatic pumping

“…Future work should consider combining the wide field-ofview of intensified near-infrared CCD imaging of lymphatic flow 6,7 with the presented high-resolution depth-resolved system for a more detailed view of lymphatic regulation and dysfunction. Future work should also focus on improving depth of imaging for clinical applications, where lymph nodes can be deeper in tissues.…”

“…Recently, near-infrared fluorescence imaging with indocyanine green (ICG) has been used for lymphography and to visualize lymphatic propulsion and structure, noninvasively, in vivo. 6,7 ICG lymphography has shown great promise for the early detection of lymphatic dysfunction, 7 the assessment of lymphedema, 8 and the detection of sentinel lymph nodes in many cancers. [9][10][11] Near-infrared fluorescence is, however, limited by light scattering and consequently has spatial resolution, which degrades with depth since ballistic photon paths are randomized at depths greater than one transport mean free path (<1 mm).…”

Emerging lymphatic imaging technologies for mouse and man

“…The majority of studies that employ NIRF imaging with ICG focus on pre-surgical and intraoperative sentinel LNM (SLNM) and dissection (31)(32)(33). While investigational camera designs have widely varying sensitivity (34,35), non-invasive NIRF imaging can detect the lymphatic vasculature located as deep as 3-4 cm beneath the tissue surface with as little as 10 μg of ICG in 0.1 ml in humans (36) using intensified camera technologies, and up to 5 μg of ICG in 10 μl in mice using electron multiplier CCD technology (37)(38)(39). In clinical studies, NIRF imaging using ICG has been demonstrated to detect subclinical lymphedema (40,41) to guide and assess lymphatico-venous anastomosis microsurgery in a case of lower extremity lymphedema (42), and has been found to be superior to lymphoscintigraphy in the diagnosis of lymphedema (43).…”