Assessment of Unspecific Near-Infrared Dyes in Laser-Induced Fluorescence Imaging of Experimental Arthritis
ABSTRACT 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.
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.
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.
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.
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ABSTRACT: Nerve injury induces long-term changes in neuronal activity in the primary somatosensory cortex (S1), which has often been implicated as the origin of sensory dysfunction. However, the cellular mechanisms underlying this phenomenon remain unclear. C-fos is an immediate early gene, which has been shown to play an instrumental role in plasticity. By developing a new platform to image real-time changes in gene expression in vivo, we investigated whether injury modulates the levels of c-fos in layer V of S1, since previous studies have suggested that these neurons are particularly susceptible to injury. The yellow fluorescent protein, ZsYellow1, under the regulation of the c-fos promoter, was expressed throughout the rat brain. A fiber-based confocal microscope that enabled deep brain imaging was utilized, and local field potentials were collected simultaneously. In the weeks following limb denervation in adult rats (n = 10), sensory stimulation of the intact limb induced significant increases in c-fos gene expression in cells located in S1, both contralateral (affected, 27.6 ± 3 cells) and ipsilateral (8.6 ± 3 cells) to the injury, compared to controls (n = 10, 13.4 ± 3 and 1.0 ± 1, respectively, p value <0.05). Thus, we demonstrated that injury activates cellular mechanisms that are involved in reshaping neuronal connections, and this may translate to neurorehabilitative potential.Journal of Molecular Neuroscience 06/2014; 54(4). DOI:10.1007/s12031-014-0347-y · 2.76 Impact Factor
Conference Paper: Effect of Nano-encapsulation on Photophysical Properties of ICG[Show abstract] [Hide abstract]
ABSTRACT: Indocyanine green (ICG) is an FDA-approved infrared chromophore used for various biomedical applications such as cardiac and hepatic function evaluation, and ophthalmic angiography. Despite its clinical applications, freely dissolved ICG binds non-specifically to various plasma proteins resulting in changes in its near infrared (NIR) emission properties and rapid elimination from the vasculature. To overcome these shortcomings, we have encapsulated ICG within polymeric nano-constructs composed of poly allylamine hydrochloride (PAH) cross-linked with di-sodium hydrogen phosphate (Na2HPO4). To optimize the photophysical properties of nano-encapsulated ICG (NE-ICG) for clinical imaging applications, we report measurements of fluorescent quantum yield (φ) of NE-ICG. Specifically, we constructed capsules of three different diameters (~130, ~240, and ~450 nm). Our preliminary results indicate that NE-ICG shows less quantum yield compared to freely-dissolved ICG. We determined that the 240 nm diameter capsule to have the highest φ and 450 nm diameter capsules to have the least φ at room temperature.Conference on Reporters, Markers, Dyes, Nanoparticles, and Molecular; 02/2011
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ABSTRACT: Background-Lipid-rich inflamed coronary plaques are prone to rupture. The purpose of this study was to assess lipid-rich inflamed plaques in vivo using fully integrated high-speed optical coherence tomography (OCT)/near-infrared fluorescence (NIRF) molecular imaging with a Food and Drug Administration-approved indocyanine green (ICG). Methods and Results-An integrated high-speed intravascular OCT/NIRF imaging catheter and a dual-modal OCT/NIRF system were constructed based on a clinical OCT platform. For imaging lipid-rich inflamed plaques, the Food and Drug Administration-approved NIRF-emitting ICG (2.25 mg/kg) or saline was injected intravenously into rabbit models with experimental atheromata induced by balloon injury and 12- to 14-week high-cholesterol diets. Twenty minutes after injection, in vivo OCT/NIRF imaging of the infrarenal aorta and iliac arteries was acquired only under contrast flushing through catheter (pullback speed up to <= 20 mm/s). NIRF signals were strongly detected in the OCT-visualized atheromata of the ICG-injected rabbits. The in vivo NIRF target-to-background ratio was significantly larger in the ICG-injected rabbits than in the saline-injected controls (P<0.01). Ex vivo peak plaque target-to-background ratios were significantly higher in ICG-injected rabbits than in controls (P<0.01) on fluorescence reflectance imaging, which correlated well with the in vivo target-to-background ratios (P<0.01; r=0.85) without significant bias (0.41). Cellular ICG uptake, correlative fluorescence microscopy, and histopathology also corroborated the in vivo imaging findings. Conclusions-Integrated OCT/NIRF structural/molecular imaging with a Food and Drug Administration -approved ICG accurately identified lipid-rich inflamed atheromata in coronary-sized vessels. This highly translatable dual-modal imaging approach could enhance our capabilities to detect high-risk coronary plaques.Circulation Cardiovascular Interventions 07/2014; 7(4). DOI:10.1161/CIRCINTERVENTIONS.114.001498 · 6.98 Impact Factor