PURPOSE: To investigate the feasibility of macrophage magnetic resonance (MR) imaging in rats by using an experimental soft-tissue infection model. MATERIALS AND METHODS: Thirteen rats with unilateral calf-muscle infection were imaged with a 4.7-T MR imager at an early chronic stage of infection (day 4 before contrast material injection, days 4-7 after injection). Eleven animals were imaged before and 3 and 24 hours after intravenous application of ultrasmall superparamagnetic iron oxide (USPIO), and eight animals were additionally imaged 48 hours and three animals 72 hours after USPIO application. Two infected rats served as controls. T1- and T2-weighted spin-echo and T2*-weighted gradient-echo sequences were applied. All animals were sacrificed, and histopathologic findings were correlated with findings on MR images. Electron microscopy was performed in two rats. For quantitative analysis, signal intensities on T2*-weighted images and T2 values on T2 maps were measured within regions of interest, and the temporal variation was analyzed by using the signed rank test. RESULTS: Visualization of USPIO-loaded macrophages was most sensitive with a T2*-weighted sequence. USPIO distribution pattern and quantitative analysis of T2 and T2* effects 3 hours after USPIO application were significantly different (P < .05) from those at 24 and 48 hours, reflecting the dynamic transit of the particle accumulation from the intravascular to the intracellular compartment by means of macrophage phagocytosis. Local signal intensity alterations could be correlated with iron-loaded macrophages at histopathologic examination. CONCLUSION: Activated macrophages in acute soft-tissue infection can be labeled with USPIOs and detected with MR imaging because of susceptibility effects. (C) RSNA, 2002.