The goal of this study was to investigate the normal MRI appearance of lymphoid organs in immuno-competent and immuno-deficient mice commonly used in research. Four mice from each of four different mouse strains (nude, NOG, C57BL/6, CB-17 SCID (SCID)) were imaged weekly for one month. Images were acquired with a 3D balanced steady state free precession (bSSFP) sequence. The volume of the lymph nodes and spleens were measured from MR images. In images of nude and SCID mice, lymph nodes sometimes contained a hyperintense region visible on MRI images. Volumes of the nodes were highly variable in nude mice. Nodes in SCID mice were smaller than in nude or C57Bl/6 mice (p<0.0001). Lymph node volumes changed slightly over time in all strains. The spleens of C57Bl/6 and nude mice were similar in size and appearance. Spleens of SCID and NOG mice were significantly smaller (p<0.0001) and abnormal in appearance. The MRI appearance of the normal lymph nodes and spleen varies considerably in the various mouse strains examined in this study. This is important to recognize in order to avoid the misinterpretation of MRI findings as abnormal when these strains are used in MRI imaging studies.
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.
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