Abstract
Iron particles are intravenously (IV) administered to label cells in vivo during magnetic resonance imaging. This technique has been extensively used to monitor immune cells in the context of inflammatory diseases. Here, we have investigated whether resting immune cells can be labeled in vivo in healthy mice before disease onset or injury, thus allowing visualization of critical early cellular events. Using 1.5 T magnetic resonance imaging, we were able to detect signal loss in bone marrow, liver, and spleen as early as 1 hour after the IV injection of superparamagnetic iron oxide nanoparticles (Feridex; 80 to 120 nm in diameter) or larger micron-sized iron oxide particles (Bangs; 0.9 μm in diameter). Results were confirmed via histology. Further, flow cytometric analysis confirmed the presence of iron-labeled CD19+ B cells, CD3+ T cells, and CD11b+ myeloid cells within the spleen and the bone marrow. Extending this work to a murine model of multiple sclerosis, we IV administered superparamagnetic iron oxide to healthy mice 1 week before inducing experimental autoimmune encephalomyelitis. Images acquired 1 week after the onset of hindlimb paralysis showed regions of signal hypointensity in the mouse brain that corresponded with iron-labeled macrophages. In summary, we show that resting immune cells in the healthy mouse liver, spleen, and bone marrow can be prelabeled with iron oxide nanoparticles. Furthermore, iron oxide preloading of immune cells in the reticuloendothelial system can be used to detect cellular infiltration in the brains of experimental autoimmune encephalomyelitis mice.
Highlights
Iron oxide nanoparticles have been extensively used to label immune cells in vivo for MRI-based tracking of cellular infiltration and inflammation in disease and injury [1,2,3,4,5,6,7]
Many studies have shown that circulating macrophages can be labeled by administration of a well-timed single bolus of iron oxide contrast agent in diseased animals, during ongoing or active inflammation, and that MRI can be used to detect these iron-labeled cells in inflammatory lesions [1,2,3,4,5,6, 9, 11,12,13,14,15, 20]
It is possible to preload macrophages with iron particles in healthy animals and to subsequently induce an inflammatory disease and detect iron-positive cells that accumulate at the site of inflammation
Summary
Iron oxide nanoparticles have been extensively used to label immune cells in vivo for MRI-based tracking of cellular infiltration and inflammation in disease and injury [1,2,3,4,5,6,7]. The accumulation of iron-labeled cells results in an area of signal loss in magnetic resonance (MR) images by causing field inhomogeneities, which shorten T2 and T2*. Both ultrasmall superparamagnetic iron oxide (USPIO; ϳ10 –30 nm) particles and standard superparamagnetic iron oxide (SPIO; ϳ30 –120 nm) particles have been used to characterize inflammation in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), whereby IV-administered iron particles were phagocytosed by macrophages and tracked to regions of active inflammation in the brain [2, 8, 9]. USPIO particles have been used this way to image inflammation in human patients with MS, atherosclerosis, stroke, myocardial infarction, and diabetes [12,13,14,15,16,17,18]
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