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Background: Collecting lymphatic vessel (CLV) dysfunction has been implicated in various diseases, including rheumatoid arthritis (RA). Previous studies in the tumor necrosis factor-transgenic (TNF-Tg) mouse model of inflammatory-erosive arthritis have demonstrated reduced joint-draining CLV contractility that correlates with arthritic severity. Clinically, RA patients with active hand arthritis exhibit significantly reduced lymphatic clearance of the web spaces adjacent to the metacarpophalangeal (MCP) joints and a reduction in total and basilic-associated CLVs on the dorsal surface of the hand by dynamic near-infrared (NIR) imaging of indocyanine green (ICG). In this pilot study, we assessed direct lymphatic drainage from MCP joints, and aimed to visualize the total lymphatic anatomy using novel dual-agent relaxation contrast magnetic resonance lymphography (DARC-MRL) in the upper extremity of healthy human subjects. Methods: Two healthy male subjects participated in the study. We performed NIR imaging following intra-dermal web space and intra-articular MCP joint injections of ICG to visualize the CLV anatomy on the dorsal surface of the hand and antecubital fossa. Subsequently, we performed conventional or DARC-MRL after intra-dermal web space and intra-articular MCP joint injections of gadolinium to evaluate the total lymphatic anatomy of the upper extremity and compare with NIR-ICG imaging. Results: NIR-ICG imaging demonstrated that web space and MCP lymphatics drain via distinct CLV tributaries. Web space draining CLVs tended to be associated with the cephalic side of the antecubital fossa, while MCP draining CLVs were localized to the basilic side of the forearm. The DARC-MRL methods used in this study did not adequately nullify the contrast in the blood vessels, and limited gadolinium-filled CLVs could be identified. Conclusion: Through the use of NIR-ICG imaging, we found that MCP joints predominantly drain into basilic CLVs in the forearm, which may explain the reduction in basilic-associated CLVs in the hands of RA patients. In healthy subjects, current DARC-MRL techniques have limited ability in identifying lymphatic structures and further refinement in this technique is necessary.
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10.1101/2020.11.04.20225995
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document_parses/pdf_json/6d5075d59724c1580e12eda215c760280778f853.json
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Near-Infrared Imaging of Indocyanine Green Identifies Novel Routes of Lymphatic Drainage from Metacarpophalangeal Joints in Healthy Human Hands
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