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

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 vivo 19F 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.

Noninvasive Longitudinal Study of a Magnetic Resonance Imaging Biomarker for the Quantification of Colon Inflammation in a Mouse Model of Colitis

“…In this respect, in a previous study, it has already been shown that perfluorocarbon particles can be used to track macrophages using MRI in a murine colitis model. 52 Similarly, a number of studies have proven that ultrasmall paramagnetic iron oxide particles may be useful to track macrophages in a number of animal models [53][54][55] and may be therefore also used to better investigate the immunological response in the DSS model.…”

In vivo MR detection of fluorine-labeled human MSC using the bSSFP sequence

“…Overall, the vast majority of studies that perform cell tracking with 19 F MRI have employed spin echo sequences. [16][17][18][19][37][38][39][40] Using the 3D bSSFP sequence, we injected and detected 1.5×10 6 Cell Sense-labeled hMSC in vivo on day 0 using a spatial resolution of 2 mm 3 (2 µL). If we assume that on day 0 all of the injected cells are present and evenly distributed, then we detected 30,000 cells per voxel.…”

Theranostic nanoemulsions for macrophage COX-2 inhibition in a murine inflammation model

“…PFC nanoemulsions have been applied in in situ labeling of macrophages and visualizing their accumulation in diseases such as arthritis [10], inflammatory bowel disease [16], cancer [17], neuroinflammation [18], and pulmonary inflammation [19]. Our lab and others have also reported dual mode nanoemulsions that incorporate fluorescent dyes and PFCs for macrophage imaging [17, 18, 20, 21] and also on the in vitro utility of nanoemulsions with therapeutic capabilities [21].…”