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Technical developments in near-infrared fluorescence (NIRF) imaging and tomography have enabled recent translation into investigational human studies. Noninvasive imaging of the lymphatic vasculature for diagnosis and assessment of function has been uniquely accomplished with NIR using indocyanine green (ICG), a nonspecific dye that has comparatively poor fluorescent properties compared to emerging dyes. Adjunct use of NIRF-ICG for (a) intraoperative sentinel lymph node mapping for cancer staging, (b) video-angiography during surgery, and (c) discrimination of malignant from benign breast lesions detected by mammography and ultrasongraphy also evidences the clinical utility of NIRF. Future NIRF imaging agents that consist of bright fluorescent dyes conjugated to disease-targeting moieties promise molecular imaging and image-guided surgery. In this review, emerging NIRF imaging is described within the context of nuclear imaging technologies that remain the “gold standard” of molecular imaging.
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Supplemental Video #1: Investigational NIRF images of the normal function of lymphatics in the arm of a healthy volunteer. Download video file (AVI) Supplemental Video #2: Stimulation of lymphatic propulsion in the foot and calf of a normal healthy volunteer before and during manual lymphatic drainage. The fluorescence from the indocyanine green (ICG) becomes scattered by tissues as the lymphatic vasculature drains into deeper vessels. The shadow on the ankle arises from black plastic that covers the injection site so that the ICCD (intensified charged coupled device) camera is not oversaturated. Reproduced with permission from Reference 25. Download video file (AVI) Supplemental Video #3: Investigational NIRF images of the lymphatics in the anteriolateral territory of the right upper arm and left hand in a 67-year-old male with grade I lymphedema presenting approximately six months after carpal tunnel syndrome surgery. Imaging was performed 11 months after onset of symptoms. Lymphatics are contrasted by IGC and show active lymphatic propulsion to the axilla. Analysis of the video demonstrates that the tortuous lymphatic vasculature drains from the edematous regions of the anterior upper arm into the medial lymph bundle. Because the lymphatics cannot be conventionally imaged with the temporal and spatial resolution shown herein, it is not known whether tortuous lymphatic vessels are the result or the cause of edema. Download video file (AVI)