Elsevier

Academic Radiology

Volume 13, Issue 1, January 2006, Pages 4-13
Academic Radiology

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

https://doi.org/10.1016/j.acra.2005.07.010Get rights and content

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.

Section snippets

NIR Dyes

Two NIR dyes were investigated: an aqueous solution of ICG (Pulsion GmbH, Munich, Germany) and a solution of the hydrophilic carbocyanine derivative 1,1′-bis-(4-sulfobutyl) indotricarbocyanine-5,5′-dicarboxylic acid diglucamide monosodium salt (SIDAG; Schering AG, Berlin, Germany). ICG is a hydrophilic anionic dye of which up to 98% is bound to plasma proteins as early as 2 seconds after IV injection. Its median lethal dose in mice ranges from 60 to 80 μmol/kg (17). The dye is excreted solely

Kinetics of NIR Fluorescence Dyes

After injection of ICG, healthy animals showed a rapid increase in NFI of the ankle joints for both dosages, with AUCs of (15 ± 3) count * s (A1) and (19 ± 8) count * s (A2). The subsequent slow decrease had a slope of –0.0032 ± 0.0001 FI units (FIU)/s (A1) and –0.0029 ± 0.0001 FIU/s (A2; Figure 2).

After injection of SIDAG, there was a slow increase in NFI throughout the interval of 150 seconds investigated, with an AUC of (220 ± 60) count * s (B1) and (290 ± 90) count * s (B2).

Animals with

Discussion

The study aims at whether normal and inflammatory joints can be differentiated by means of the pharmacokinetic behavior of nonspecific dyes, determined by means of fluorescence imaging. More specifically, the experimental study was conducted to investigate two nonspecific NIR dyes in terms of their pharmacokinetic behavior in normal and inflammatory ankle joints of mice.

The animal model of Lyme arthritis used in this study is based on the assumption that systemic inflammation is induced by

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