title: Assessment of unspecific near-infrared dyes in laser-induced fluorescence imaging of experimental arthritis.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Radiology, Charité, Universitätsmedizin Berlin, Campus Charité Mitte, Schumannstrasse 20/21, 10098 Berlin, Germany. thom.fischer@charite.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Fischer
authors.forename: Ines
authors.initials: I
authors.lastname: Gemeinhardt
authors.forename: Susanne
authors.initials: S
authors.lastname: Wagner
authors.forename: Dorothee V
authors.initials: DV
authors.lastname: Stieglitz
authors.forename: Jörg
authors.initials: J
authors.lastname: Schnorr
authors.forename: Kay-Geert A
authors.initials: KG
authors.lastname: Hermann
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: Kai
authors.initials: K
authors.lastname: Licha
authors.forename: Michael
authors.initials: M
authors.lastname: Schirner
authors.forename: Veit
authors.initials: V
authors.lastname: Krenn
authors.forename: Thomas
authors.initials: T
authors.lastname: Kamradt
authors.forename: Matthias
authors.initials: M
authors.lastname: Taupitz
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001169:Arthritis, Experimental / Q000175:diagnosis*; D002232:Carbocyanines; D004396:Coloring Agents; D003287:Contrast Media; D005453:Fluorescence; D007208:Indocyanine Green; D007834:Lasers; D008193:Lyme Disease / Q000175:diagnosis; D051379:Mice; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D018709:Statistics, Nonparametric
chemical_list: C430879:1,1'-bis-(4-sulfobutyl)indotricarbocyanine-5,5'-dicarboxylic acid diglucamide; D002232:Carbocyanines; D004396:Coloring Agents; D003287:Contrast Media; D007208:Indocyanine Green