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

• Published in: Journal of biomedical optics Vol. 17; no. 10; pp. 1060081 - 1-106008-9
• Main Authors: Gemeinhardt, Ines, Puls, Dorothee, Gemeinhardt, Ole, Taupitz, Matthias, Wagner, Susanne, Schnorr, Beatrix, Licha, Kai, Schirner, Michael, Ebert, Bernd, Petzelt, Diethard, Macdonald, Rainer, Schnorr, Jörg
• Format: Journal Article
• Language: English
• Published: United States 01.10.2012
• Subjects: Animals; Arthritis; Arthritis, Experimental - metabolism; Arthritis, Experimental - pathology; Carbocyanines - chemistry; Carbocyanines - pharmacokinetics; Contrast Media - chemistry; Contrast Media - pharmacokinetics; Correlation analysis; Dyes; Female; Fluorescence; Fluorescent Dyes - chemistry; Fluorescent Dyes - pharmacokinetics; Gadolinium - chemistry; Gadolinium - pharmacokinetics; Histocytochemistry; Imaging; Joints - anatomy & histology; Joints - chemistry; Joints - metabolism; Joints - pathology; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Optical Imaging; Rats; Spectroscopy, Near-Infrared - methods; Surgical implants
• ISSN: 1083-3668; 1560-2281; 1560-2281
• DOI: 10.1117/1.JBO.17.10.106008

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.