Contrast enhancement by lipid-based MRI contrast agents in mouse atherosclerotic plaques; a longitudinal study
Article first published online: 29 OCT 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Contrast Media & Molecular Imaging
Volume 8, Issue 1, pages 63–71, January/February 2013
How to Cite
den Adel, B., van der Graaf, L. M., Que, I., Strijkers, G. J., Löwik, C. W., Poelmann, R. E. and van der Weerd, L. (2013), Contrast enhancement by lipid-based MRI contrast agents in mouse atherosclerotic plaques; a longitudinal study. Contrast Media Mol Imaging, 8: 63–71. doi: 10.1002/cmmi.1496
- Issue published online: 29 OCT 2012
- Article first published online: 29 OCT 2012
- Manuscript Accepted: 3 AUG 2012
- Manuscript Revised: 27 JUL 2012
- Manuscript Received: 6 MAR 2012
- paramagnetic contrast agents
The use of contrast-enhanced MRI to enable in vivo specific characterization of atherosclerotic plaques is increasing. In this study the intrinsic ability of two differently sized gadolinium-based contrast agents to enhance atherosclerotic plaques in ApoE−/− mice was evaluated with MRI. We obtained a kinetic profile for contrast enhancement, as the literature data on optimal imaging time points is scarce, and assessed the longer-term kinetics. Signal enhancement in the wall of the aortic arch, following intravenous injection of paramagnetic micelles and liposomes, was followed for 1 week. In vivo T1-weighted MRI plaque enhancement characteristics were complemented by fluorescence microscopy of NIR664 incorporated in the contrast agents and quantification of tissue and blood Gd–DTPA. Both micelles and liposomes enhanced contrast in T1-weighted MR images of plaques in the aortic arch. The average contrast-to-noise ratio increased after liposome or micelle injection to 260 or 280% respectively, at 24 h after injection, compared with a pre-scan. A second wave of maximum contrast enhancement was observed around 60–72 h after injection, which only slowly decreased towards the 1 week end-point. Confocal fluorescence microscopy and whole body fluorescence imaging confirmed MRI-findings of accumulation of micelles and liposomes. Plaque permeation of contrast agents was not strongly dependent on the contrast agent size in this mouse model. Our results show that intraplaque accumulation over time of both contrast agents leads to good plaque visualization for a long period. This inherent intraplaque accumulation might make it difficult to discriminate passive from targeted accumulation. This implies that, in the development of targeted contrast agents on a lipid-based backbone, extensive timing studies are required. Copyright © 2012 John Wiley & Sons, Ltd.