Abstract 19967: Tracking Monocytes Homing to Atherosclerosis by MRI
Monocyte-endothelium interaction plays a crucial role in atherogenesis. The purpose of this study is to develop a non-invasive imaging approach to track monocyte homing to the arterial wall containing atherosclerotic lesions in a mouse model. Monocytes were isolated from the spleen of mice using CD11b antibody-coated magnetic beads, treated with IL-1beta at 10ng/ml for 3 hours, and then labeled with micron-sized paramagnetic iron oxide particles (MPIO). Monocytes were efficiently labeled (72±14%) by MPIO after incubating with labeling media containing 12.5 μg iron per ml for 60 min. This labeling protocol Resultsed in good viability of the labeled cells (80%). One million labeled monocytes were injected via the tail vein into LDLR-/- mice, which had been on high fat diet for 9 months. Two days after injection, magnetic resonance imaging (MRI) was performed on a 9.4T horizontal bore Varian Direct Drive system interfaced with a 1H quadrature volume coil. The mouse was maintained under isoflurane and all images were acquired under cardiac and respiratory double gating. A fast spin echo sequence was optimized to achieve visualization of arterial wall. The aortic anatomy and aortic wall was clearly visualized as the result of effective suppression of the blood signal in the lumen and high spatial resolution (117 × 94 × 800 μm). The extensive atherosclerotic plaques which developed in the aorta, particularly in the aortic root and arch in the LDLR-/- mouse were readily identified by MRI. MPIO-associated hypointense MRI signals were detectable in atherosclerotic plaques in vivo and ex vivo. Histological analysis confirmed that injected monocytes homed to the atherosclerotic plaque by attaching to endothelium and migrating into the arterial wall. Labeled monocytes were also found in vasa vasorum region, which contains microvasculature feeding the aorta. These data support the use of MRI for non-invasive tracking of monocyte homing. The process of monocyte homing can potentially be compared among subjects with genetic or pharmacological manipulations that are relevant to artherogenesis.
Acknowledgements: Grants from AHA[0735397N], the Translational Biomedical Imaging Center and Program in Targeted Therapeutics of the ITMAT, UPenn are gratefully acknowledged.
- © 2010 by American Heart Association, Inc.