title: Quantitative imaging of lymph function.
abstract: Functional lymphatic imaging was demonstrated in the abdomen and anterior hindlimb of anesthetized, intact Yorkshire swine by using near-infrared (NIR) fluorescence imaging following intradermal administration of 100-200 microl of 32 microM indocyanine green (ICG) and 64 microM hyaluronan NIR imaging conjugate to target the lymph vascular endothelial receptor (LYVE)-1 on the lymph endothelium. NIR fluorescence imaging employed illumination of 780 nm excitation light ( approximately 2 mW/cm(2)) and collection of 830 nm fluorescence generated from the imaging agents. Our results show the ability to image the immediate trafficking of ICG from the plexus, through the vessels and lymphangions, and to the superficial mammary, subiliac, and middle iliac lymph nodes, which were located as deep as 3 cm beneath the tissue surface. "Packets" of ICG-transited lymph vessels of 2-16 cm length propelled at frequencies of 0.5-3.3 pulses/min and velocities of 0.23-0.75 cm/s. Lymph propulsion was independent of respiration rate. In the case of the hyaluronan imaging agent, lymph propulsion was absent as the dye progressed immediately through the plexus and stained the lymph vessels and nodes. Lymph imaging required 5.0 and 11.9 microg of ICG and hyaluronan conjugate, respectively. Our results suggest that microgram quantities of NIR optical imaging agents and their conjugates have a potential to image lymph function in patients suffering from lymph-related disorders.
authors.affiliation: Division of Molecular Imaging, Department of Radiology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Sharma
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: John C
authors.initials: JC
authors.lastname: Rasmussen
authors.forename: Amit
authors.initials: A
authors.lastname: Joshi
authors.forename: Jessica P
authors.initials: JP
authors.lastname: Houston
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Adams
authors.forename: Arlin
authors.initials: A
authors.lastname: Cameron
authors.forename: Shi
authors.initials: S
authors.lastname: Ke
authors.forename: Sunkuk
authors.initials: S
authors.lastname: Kwon
authors.forename: Michel E
authors.initials: ME
authors.lastname: Mawad
authors.forename: Eva M
authors.initials: EM
authors.lastname: Sevick-Muraca
mesh_terms: D000005:Abdomen; D000818:Animals; D004729:Endothelium, Lymphatic / Q000378:metabolism; D005240:Feasibility Studies; D005456:Fluorescent Dyes / Q000008:administration & dosage; D006614:Hindlimb; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000008:administration & dosage; D007090:Image Interpretation, Computer-Assisted; D007208:Indocyanine Green / Q000008:administration & dosage; D007271:Injections, Intradermal; D008196:Lymph / Q000378:metabolism*; D008206:Lymphatic Diseases / Q000175:diagnosis / Q000378:metabolism; D008208:Lymphatic System / Q000378:metabolism*; D011673:Pulsatile Flow; D013050:Spectrometry, Fluorescence; D019265:Spectroscopy, Near-Infrared; D013552:Swine; D013997:Time Factors
chemical_list: D005456:Fluorescent Dyes; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D007208:Indocyanine Green