AbstractPurpose:To test the ability of MION‐47 enhanced MRI to identify tissue macrophage infiltration in a rabbit model of aortic valve sclerosis (AVS).Materials and Methods:The aortic valves of control and cholesterol‐fed New Zealand White rabbits were imaged in vivo pre‐ and 48 h post‐intravenous administration of MION‐47 using a 1.5 Tesla (T) MR clinical scanner and a CINE fSPGR sequence. MION‐47 aortic valve cusps were imaged ex vivo on a 3.0T whole‐body MR system with a custom gradient insert coil and a three‐dimensional (3D) FIESTA sequence and compared with aortic valve cusps from control and cholesterol‐fed contrast‐free rabbits. Histopathological analysis was performed to determine the site of iron oxide uptake.Results:MION‐47 enhanced the visibility of both control and cholesterol‐fed rabbit valves in in vivo images. Ex vivo image analysis confirmed the presence of significant signal voids in contrast‐administered aortic valves. Signal voids were not observed in contrast‐free valve cusps. In MION‐47 administered rabbits, histopathological analysis revealed iron staining not only in fibrosal macrophages of cholesterol‐fed valves but also in myofibroblasts from control and cholesterol‐fed valves.Conclusion:Although iron oxide labeling of macrophage infiltration in AVS has the potential to detect the disease process early, a macrophage‐specific iron compound rather than passive targeting may be required. J. Magn. Reson. Imaging 2010;31:110–116. © 2009 Wiley‐Liss, Inc.