Objectives To use non-invasive conventional and molecular magnetic resonance imaging (MRI) to detect and characterize abdominal aortic aneurysms (AAAs) in vivo. Background Collagen is an essential constituent of aneurysms. Non-invasive MRI of collagen may represent an opportunity to help detect and better characterize AAA and initiate intervention. Methods We used an AAA C57BL/6 mouse model where a combination of angiotensin-II infusion and TGF-β neutralization results in AAA formation with incidence of aortic rupture. High-resolution multi-sequence MRI was performed to characterize the temporal progression of AAA. To allow molecular MRI of collagen, paramagnetic/fluorescent micellar nanoparticles functionalized with a collagen-binding protein (CNA-35) were intravenously administered. In vivo imaging results were corroborated with immunohistochemistry and confocal fluorescence microscopy. Results High-resolution multi-sequence MRI allowed the visualization of the primary fibrotic response in the aortic wall. As the aneurysm progressed, the formation of a secondary channel or dissection was detected. Further analysis revealed a dramatic increase of the aortic diameter. Injection of CNA-35 micelles resulted in a significant higher MR signal enhancement in the aneurysmal wall compared to non-specific micelles. Histological studies demonstrated the presence of collagen in regions of MR signal enhancement and confocal microscopy proved the precise colocalization of CNA-35 micelles with collagen-I. In addition, in a proof of concept experiment, we have shown the potential of CNA-35 micelles to discriminate between stable AAA lesions and aneurysms that were likely to rapidly progress/rupture. Conclusion Multi-sequence MRI allowed longitudinal monitoring of AAA progression while the presence of collagen was visualized by nanoparticle-enhanced MRI.

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.