Nanometer-sized materials offer a wide range of applications in biomedical technologies, particularly imaging and diagnostics. Current scaffolds in the nanometer range predominantly make use of inorganic particles, organic polymers or natural peptide-based macromolecules. In contrast we hereby report a supramolecular approach for the preparation of self-assembled dendritic-like nanoparticles for applications as MRI contrast agents. This strategy combines the benefits from low molecular weight imaging agents with the ones of high molecular weight. Their in vitro properties are confirmed by in vivo measurements: post injection of well-defined and meta-stable nanoparticles allows for high-resolution blood-pool imaging, even at very low Gd(III) doses. These dynamic and modular imaging agents are an important addition to the young field of supramolecular medicine using well-defined nanometer-sized assemblies.

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Objectives We report here on the pre-clinical MRI characterization of an apoE−/− mouse model of stable and vulnerable carotid artery atherosclerotic plaques, which were induced by a tapered restriction (cast) around the artery. Specific focus was on the quantification of the wall shear stress, which is considered a key player in the development of the plaque phenotype. Materials and methods In vivo MRI was performed at 9.4 T. The protocol consisted of time-of-flight angiography, highresolution T1-and T2-weighted black-blood imaging and phase-contrast flow velocity imaging as function of time in the cardiac cycle. Wall shear stress was determined by fitting the flow profile to a quadratic polynomial. Results Time-of-flight angiography confirmed preservation of blood flow through the carotid arteries in all cases. T1-and T2-weighted MRI resulted in high-resolution images in which the position of the cast, luminal narrowing introduced by cast and plaque, as well as the arterial wall could be well identified. Laminar flow with low wall shear stress (11.2 ± 5.2 Pa) was measured upstream to the cast at the position of the vulnerable plaque. Downstream to the cast at the position of the stable plaque, the apparent velocities were low, which Conclusions Flow velocities and wall shear stress were successfully measured in this mouse model of stable and unstable plaque. The presented tools can be used to provide valuable insights in the pathogenesis of atherosclerosis.

Treatment of disease can only be effective when timely and accurate diagnosis of the pathology is achieved. More precise diagnosis can be accomplished if the underlying molecular processes involved in the pathology can be imaged in vivo. This is the field of molecular imaging, which aims to visualize cellular function and molecular processes in living organisms in a non-invasive way. With that aim, molecular markers are specifically targeted by imaging contrast agents. Molecular MRI needs powerful targeted contrast agents. For that purpose, target-specific gadolinium-containing paramagnetic and superparamagnetic, iron oxide-based micelles have been developed. Micelles are lipid-based nanoparticles which are biocompatible and carry a high payload of MR contrast-generating agent. The coupling of high-affinity ligands makes the micelles target-specific. Additionally, this lipid-based micelle platform allows for incorporation of contrast generating molecules for other imaging modalities, e.g., fluorescence or nuclear imaging. This permits applications for multiple imaging modalities, making micelles a highly versatile contrast agent.

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