Article
Assaying macrophage activity in a murine model of inflammatory bowel disease using fluorine-19 MRI

https://doi.org/10.1038/labinvest.2012.7Get rights and content
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Abstract

Macrophages have an important role in the pathogenesis of most chronic inflammatory diseases. A means of non-invasively quantifying macrophage migration would contribute significantly towards our understanding of chronic inflammatory processes and aid the evaluation of novel therapeutic strategies. We describe the use of a perfluorocarbon tracer reagent and in vivo19F magnetic resonance imaging (MRI) to quantify macrophage burden longitudinally. We apply these methods to evaluate the severity and three-dimensional distribution of macrophages in a murine model of inflammatory bowel disease (IBD). MRI results were validated by histological analysis, immunofluorescence and quantitative real-time polymerase chain reaction. Selective depletion of macrophages in vivo was also performed, further validating that macrophage accumulation of perfluorocarbon tracers was the basis of 19F MRI signals observed in the bowel. We tested the effects of two common clinical drugs, dexamethasone and cyclosporine A, on IBD progression. Whereas cyclosporine A provided mild therapeutic effect, unexpectedly dexamethasone enhanced colon inflammation, especially in the descending colon. Overall, 19F MRI can be used to evaluate early-stage inflammation in IBD and is suitable for evaluating putative therapeutics. Due to its high macrophage specificity and quantitative ability, we envisage 19F MRI having an important role in evaluating a wide range of chronic inflammatory conditions mediated by macrophages.

Keywords

bowel
inflammation
macrophage
MRI
perfluorocarbon

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Perfluorocarbon imaging agents and 19F magnetic resonance imaging can be used to quantify macrophage burden longitudinally. These methods can be used to assess the topology and severity of macrophages in inflammatory bowel disease and are effective for evaluating early-stage inflammation and therapeutics.