Adipose Tissue Macrophages: MR Tracking to Monitor Obesity-associated Inflammation

Abstract

To investigate whether cellular imaging by using ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging can allow detection and quantification of adipose tissue macrophage-related inflammation within adipose tissue in a mouse model. Experimental protocols were conducted in accordance with French government policies. Adipose tissue macrophages were detected and quantified with a 4.7-T MR imager in ob/ob obese mice on the basis of the signal variance of adipose tissue triggered by injection of P904 iron oxide nanoparticles (USPIO). Mice were either intravenously injected with 1000 μmol of iron per kilogram of body weight of P904 (10 ob/ob and 11 ob/+) or used as noninjected control animals (seven ob/ob and six ob/+). Three-dimensional T2*-weighted gradient-echo MR images were acquired 10 days after intravenous injection. MR imaging signal variance in mice was correlated to adipose tissue macrophage quantification by using monoclonal antibody to F4/80 immunostaining, to proinflammatory marker quantification by using reverse transcription polymerase chain reaction (CCl2, Tnfα, Emr1), and to P904 quantification by using electron paramagnetic resonance imaging. Quantitative data were compared by using the Mann-Whitney or Student t test, and correlations were performed by using the Pearson correlation test. MR imaging measurements showed a significant increase in adipose tissue signal variance in ob/ob mice compared with ob/+ controls or noninjected animals (P < .0001), which was consistent with increased P904 uptake by adipose tissue in ob/ob mice. There was a significant and positive correlation between adipose tissue macrophage quantification at MR imaging and P904 iron oxide content (r = 0.87, P < .0001), adipose tissue macrophage-related inflammation at immunohistochemistry (r = 0.60, P < .01), and adipose tissue proinflammatory marker expression (r = 0.55, 0.56, and 0.58 for CCl2, Tnfα, and Emr1, respectively; P < .01). P904 USPIO-enhanced MR imaging is potentially a tool for noninvasive assessment of adipose tissue inflammation during experimental obesity. These results provide the basis for translation of MR imaging into clinical practice as a marker of patients at risk for metabolic syndrome.