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Longitudinal quantification of inflammation in the murine dextran sodium sulfate-induced colitis model using μPET/CT

Authors

  • P. Hindryckx MD,

    Corresponding author
    1. Faculty of Medicine and Health Sciences, Department of Hepatology and Gastroenterology, Ghent University, Ghent, Belgium
    • Department of Gastroenterology, Ghent University Hospital, De Pintelaan 185, 3K12IE, B-9000 Ghent, Belgium
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    • The first two authors contributed equally.

  • S. Staelens PhD,

    1. Medical Signal and Image Processing group, Ghent University-IBBT, Ghent, Belgium
    2. Faculty of Medicine, Molecular Imaging Center Antwerp, Antwerp University, Antwerp, Belgium
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    • The first two authors contributed equally.

  • L. Devisscher MSc,

    1. Faculty of Medicine and Health Sciences, Department of Hepatology and Gastroenterology, Ghent University, Ghent, Belgium
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  • S. Deleye MSc,

    1. Medical Signal and Image Processing group, Ghent University-IBBT, Ghent, Belgium
    2. Faculty of Medicine, Molecular Imaging Center Antwerp, Antwerp University, Antwerp, Belgium
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  • F. De Vos PhD,

    1. Faculty of Pharmaceutical Sciences, Radiopharmacy, Ghent University, Ghent, Belgium
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  • L. Delrue MD,

    1. Faculty of Medicine and Health Sciences, Department of Radiology, Ghent University, Ghent, Belgium
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  • H. Peeters PhD,

    1. Faculty of Medicine and Health Sciences, Department of Hepatology and Gastroenterology, Ghent University, Ghent, Belgium
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  • D. Laukens PhD,

    1. Faculty of Medicine and Health Sciences, Department of Hepatology and Gastroenterology, Ghent University, Ghent, Belgium
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  • M. De Vos PhD

    1. Faculty of Medicine and Health Sciences, Department of Hepatology and Gastroenterology, Ghent University, Ghent, Belgium
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  • Supported by a grant from the Fund for Scientific Research (Aspirant mandaat-FWO Vlaanderen to Pieter Hindryckx) by Ghent University, by the Institute for BroadBand Technology and imaging (IBBT), and by the BOF fund of Antwerp University. There are no financial disclosures to a company related to the submitted article.

Abstract

Background:

This study investigates whether deoxy-2-[18F]fluoro-d-glucose (FDG) micro-positron emission tomography (μPET)/computed tomography (CT) can serve as a tool for monitoring of the commonly used dextran sodium sulfate (DSS)-induced murine model of inflammatory bowel disease (IBD).

Methods:

DSS-colitis was induced in Sv129 mice. In a first experiment, four animals were serially scanned with CT and FDG-μPET on days 0, 3, 7, 11, and 14. The ratio of the mean voxel count of the PET images in the colon and the brain was compared with the histological inflammation score and the colonic myeloperoxidase levels. A second experiment was performed to investigate whether FDG-μPET was able to detect differences in inflammation between two DSS-treated groups, one receiving placebo (n = 4) and one receiving dimethyloxalylglycine (DMOG) (n = 4), a compound that protects against DSS-induced colitis.

Results:

The progression of the colonic/brain FDG-signal ratio (over days 0–14) agreed with the predicted histological inflammation score, obtained from a parallel DSS-experiment. Moreover, the quantification of normalized colonic FDG-activity at the final timepoint (day 14) showed an excellent correlation with both the MPO levels (Spearman's rho = 1) and the histological inflammation score (Spearman's rho = 0.949) of the scanned mice. The protective action of DMOG in DSS colitis was clearly demonstrated with FDG-μPET/CT (normalized colonic FDG-activity DMOG versus placebo: P < 0.05).

Conclusions:

FDG-μPET-CT is a feasible and reliable noninvasive method to monitor murine DSS-induced colitis. The implementation of this technique in this widely used IBD model opens a new window for pathophysiological research and high-throughput screening of potential therapeutic compounds in preclinical IBD research. (Inflamm Bowel Dis 2010;)

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