Assessment of Unspecific Near-Infrared Dyes in Laser-Induced Fluorescence Imaging of Experimental Arthritis

Fischer, Thomas; Gemeinhardt, Ines; Wagner, Susanne; Stieglitz, Dorothee v.; Schnorr, Jörg; Hermann, Kay-Geert A.; Ebert, Bernd; Petzelt, Diethard; MacDonald, Rainer; Licha, Kai; Schirner, Michael; Krenn, Veit; Kamradt, Thomas; Taupitz, Matthias

doi:10.1016/j.acra.2005.07.010

« Previous Next »Academic Radiology
Volume 13, Issue 1 , Pages 4-13, January 2006

Assessment of Unspecific Near-Infrared Dyes in Laser-Induced Fluorescence Imaging of Experimental Arthritis

Thomas Fischer, MD
- Department of Radiology, Charité, Universitätsmedizin Berlin, Campus Charité Mitte, Schumannstrasse 20/21, 10098 Berlin, Germany
- Address correspondence to: T.F Department of Radiology, Charité, Universitätsmedizin Berlin, Campus Charité Mitte, Schumannstrasse 20/21, 10098 Berlin, Germany
Ines Gemeinhardt, DVM
- Department of Radiology, Charité, Universitätsmedizin Berlin, Campus Charité Mitte, Schumannstrasse 20/21, 10098 Berlin, Germany
Susanne Wagner, DVM
- Department of Radiology, Charité, Universitätsmedizin Berlin, Campus Charité Mitte, Schumannstrasse 20/21, 10098 Berlin, Germany
Dorothee v. Stieglitz, DVM
- Department of Radiology, Charité, Universitätsmedizin Berlin, Campus Charité Mitte, Schumannstrasse 20/21, 10098 Berlin, Germany
Jörg Schnorr, DVM
- Department of Radiology, Charité, Universitätsmedizin Berlin, Campus Charité Mitte, Schumannstrasse 20/21, 10098 Berlin, Germany
Kay-Geert A. Hermann, MD
- Department of Radiology, Charité, Universitätsmedizin Berlin, Campus Charité Mitte, Schumannstrasse 20/21, 10098 Berlin, Germany
Bernd Ebert, PhD
- Physikalisch-Technische Bundesanstalt, Department of Biomedical Optics
Diethard Petzelt
- Physikalisch-Technische Bundesanstalt, Department of Biomedical Optics
Rainer MacDonald, PhD
- Physikalisch-Technische Bundesanstalt, Department of Biomedical Optics
Kai Licha, PhD
- Schering AG, Research Laboratories, Berlin, Germany
Michael Schirner, MD
- Schering AG, Research Laboratories, Berlin, Germany
Veit Krenn, MD
- Department of Pathology, Charité, Universitätsmedizin Berlin, Campus Charité Mitte, Schumannstrasse 20/21, 10098 Berlin, Germany
Thomas Kamradt, MD
- Department of Rheumatology, Charité, Universitätsmedizin Berlin, Campus Charité Mitte, Schumannstrasse 20/21, 10098 Berlin, Germany
Matthias Taupitz, MD, PhD
- Department of Radiology, Charité, Universitätsmedizin Berlin, Campus Charité Mitte, Schumannstrasse 20/21, 10098 Berlin, Germany

Received 27 May 2005; received in revised form 14 July 2005; accepted 18 July 2005.

Objective

The aim of the study is to evaluate in vivo fluorescence imaging of experimental inflammatory joint disease by applying two different near-infrared (NIR) dyes in a model of Borrelia-induced Lyme arthritis.

Materials and Methods

Forty mice, 20 with Lyme arthritis and 20 controls, were examined. Two nonspecific NIR carbocyanine dyes, indocyanine green (ICG) and a hydrophilic carbocyanine derivative (1,1′-bis-[4-sulfobutyl] indotricarbocyanine-5,5′-dicarboxylic acid diglucamide monosodium salt [SIDAG]), were administered intravenously at two doses. Fluorescence images were acquired before and during 120 seconds after injection of cyanine dyes. For both dyes, the area under the curve (AUC) was determined for the interval between 40 and 80 seconds after injection. In addition, the slope of the signal decrease was compared among animal groups. Results were compared with histological findings.

Results

The general temporal fluorescence intensity course for ICG was characterized by a rapid increase, with a peak at 40–50 seconds followed by a decrease; conversely for SIDAG, by a slow increase. AUC analysis for both dyes showed that the fluorescence signal differed significantly between controls and arthritic animals (P < .05). Within these groups, there were significant differences between the two doses investigated. ICG differed significantly between control and arthritic animals in the slope of the signal decrease for both doses investigated (P < .05). Histological examination showed early stages of inflammation in arthritic animals.

Conclusions

NIR fluorescence imaging based on the pharmacokinetic behavior of ICG or SIDAG is a promising approach to detect inflammatory joint changes of experimental arthritis. Moreover, SIDAG is suited to differentiate inflammatory and noninflammatory joints 24 hours after dye application.

Key Words: Arthritis , near-infrared (NIR) fluorescence imaging , experimental study