title: Near-infrared fluorescence imaging of experimentally collagen-induced arthritis in rats using the nonspecific dye tetrasulfocyanine in comparison with gadolinium-based contrast-enhanced magnetic resonance imaging, histology, and clinical score.
abstract: Using 15 rats with collagen-induced arthritis (30 joints) and 7 control rats (14 joints), we correlated the intensity of near-infrared fluorescence (NIRF) of the nonspecific dye tetrasulfocyanine (TSC) with magnetic resonance imaging (MRI), histopathology, and clinical score. Fluorescence images were obtained in reflection geometry using a NIRF camera system. Normalized fluorescence intensity (INF) was determined after intravenous dye administration on different time points up to 120 min. Contrast-enhanced MRI using gadodiamide was performed after NIRF imaging. Analyses were performed in a blinded fashion. Histopathological and clinical scores were determined for each ankle joint. INF of moderate and high-grade arthritic joints were significantly higher (p<0.005) than the values of control and low-grade arthritic joints between 5 and 30 min after TSC-injection. This result correlated well with post-contrast MRI signal intensities at about 5 min after gadodiamide administration. Furthermore, INF and signal increase on contrast-enhanced MRI showed high correlation with clinical and histopathological scores. Sensitivities and specificities for detection of moderate and high-grade arthritic joints were slightly lower for NIRF imaging (89%/81%) than for MRI (100%/91%). NIRF imaging using TSC, which is characterized by slower plasma clearance compared to indocyanine green (ICG), has the potential to improve monitoring of inflamed joints.
authors.affiliation: Department of Radiology, Charité-Universitaetsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10117 Berlin, Germany. ines.gemeinhardt@charite.de
authors.forename: Ines
authors.initials: I
authors.lastname: Gemeinhardt
authors.forename: Dorothee
authors.initials: D
authors.lastname: Puls
authors.forename: Ole
authors.initials: O
authors.lastname: Gemeinhardt
authors.forename: Matthias
authors.initials: M
authors.lastname: Taupitz
authors.forename: Susanne
authors.initials: S
authors.lastname: Wagner
authors.forename: Beatrix
authors.initials: B
authors.lastname: Schnorr
authors.forename: Kai
authors.initials: K
authors.lastname: Licha
authors.forename: Michael
authors.initials: M
authors.lastname: Schirner
authors.forename: Bernd
authors.initials: B
authors.lastname: Ebert
authors.forename: Diethard
authors.initials: D
authors.lastname: Petzelt
authors.forename: Rainer
authors.initials: R
authors.lastname: Macdonald
authors.forename: Jörg
authors.initials: J
authors.lastname: Schnorr
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology*; D002232:Carbocyanines / Q000737:chemistry* / Q000493:pharmacokinetics; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000493:pharmacokinetics; D005682:Gadolinium / Q000737:chemistry* / Q000493:pharmacokinetics; D006651:Histocytochemistry; D007596:Joints / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D061848:Optical Imaging; D051381:Rats; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
chemical_list: D002232:Carbocyanines; D003287:Contrast Media; D005456:Fluorescent Dyes; D005682:Gadolinium