MR imaging of in vivo recruitment of iron oxide-labeled macrophages in experimentally induced soft-tissue infection in mice.

Abstract

To evaluate the feasibility of magnetic resonance (MR) imaging in depicting in vivo recruitment of iron oxide-labeled macrophages in experimentally induced soft-tissue infection. The study was performed according to the guidelines of the U.S. National Institutes of Health and recommendations of the committee on animal research. The protocol was approved by the local institutional review committee on animal care. Experimental soft-tissue infection in 12 mice was induced by inoculation with a 5 x 10(7) colony-forming units of Staphylococcus aureus into the left calf. Peritoneal macrophages were harvested from thioglycollate-treated mice, cultured, and labeled with iron oxide in vitro. The iron oxide-labeled macrophage (macrophage group, n = 6) or iron oxide solution (control group, n = 6) was administered through the tail vein. The left calf of the mice was imaged on days 2 and 3 with a 4.7-T MR unit. Changes in relative signal intensity (SI) and pattern of contrast material enhancement (macrophage distribution) were analyzed and compared with histopathologic findings. Statistical analysis was performed with the Wilcoxon matched-pairs signed rank test. On MR images obtained 24 hours after administration of macrophage labeled with iron oxide, a band-shaped lower SI zone was noted in the abscess wall, which corresponded to the distribution of the iron oxide-labeled macrophages at histopathologic examination. The relative SI of the abscess wall significantly decreased after injection of iron oxide-labeled macrophages (median, 0.42) compared with that before injection (median, 1.23) (P = .031). In the control group, the SI change after administration of iron oxide solution was not significant (P = .688). Homing of intravenously administered iron oxide-labeled macrophages can be monitored with MR imaging and may provide a tool to investigate interactions between macrophages and the invading pathogens.