A new way to analyze supramolecular dendritic architectures is reported by making use of (13)C NMR and (31)P NMR. Two ethylene glycol guest molecules have been synthesized containing a (13)C labeled carboxylic acid headgroup (2) and a phosphonic acid headgroup (3). The binding of these guests to urea-adamantyl modified poly(propylene imine) dendrimers has been investigated with (13)C NMR and (31)P NMR next to 1D and 2D (1)H NMR techniques. Different amounts of guest 2 have been added to fifth generation dendrimer 1e, and the observed chemical shift values in (13)C NMR were fitted to a model that assumes 1:1 binding between guest and binding site. An association constant of 400 +/- 95 M(-)(1) is obtained for guest 2 with 41 binding sites per dendrimer. When different amounts of phosphonic acid guest 3 are added to dendrimer 1e, two different signals are observed in (31)P NMR. Deconvolution gives the fractions of free and bound guest, resulting in an association constant of (4 +/- 3) x 10(4) M(-)(1) and 61 +/- 1 binding sites. A statistical analysis shows that guest 2 forms a "polydisperse supramolecular aggregate", while guest 3 is able to form a "monodisperse supramolecular aggregate" when the amount of guest is high enough. The NMR results are compared with dynamic light scattering experiments, and a remarkable agreement is found. Phosphonic acid guest 3 is able to exchange with guest 2, which is in agreement with the obtained association constants, and shows that these techniques can be used to analyze multicomponent dendritic aggregates.

The cardiac muscle architecture lies at the basis of the mechanical and electrical properties of the heart, and dynamic alterations in fiber structure are known to be of prime importance in healing and remodeling after myocardial infarction. In this study, left ventricular remodeling was characterized using diffusion tensor imaging (DTI) in a mouse model of myocardial infarction. Myocardial infarction was induced in mice by permanent ligation of the left anterior descending coronary artery. Serial ex vivo DTI measurements were performed 7, 14, 28, and 60 days after ligation. Apparent diffusion coefficient, fractional anisotropy, the three eigenvalues of the diffusion tensor, and the myofiber disarray served as readout parameters. After myocardial infarction, the mouse hearts displayed extreme wall thinning in the infarcted area, which covered large parts of the apex and extended into the free wall up to the equator. Average heart mass increased by 70% 7-60 days after infarction. Histological analysis showed that the infarct at 7 days consisted of unstructured tissue with residual necrosis and infiltration of macrophages and myofibroblasts. At 14 days after infarction, the necrotic tissue had disappeared and collagen fibers were starting to appear. From 28 to 60 days, the infarct had fully developed into a mature scar. DTI parameters showed dynamic changes as a function of time after infarction. The apparent diffusion coefficient in the infarcted region was lower than in remote regions and increased as a function of time after infarction. The fractional anisotropy was higher in the infarcted region and was maximum at 28 days, which was attributed to the development of structured collagen fibers. Myofiber disarray, which was analyzed by considering the alignment of fibers in neighboring voxels, was significantly higher in infarcted regions. DTI provides a valuable non-destructive tool for characterizing structural remodeling in diseased myocardium.

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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.

The peculiar properties of osmotically shrunken liposomes acting as magnetic resonance imaging-chemical exchange saturation transfer (MRI-CEST) contrast agents have been investigated. Attention has been primarily devoted to assessing the contribution arising from encapsulated and incorporated paramagnetic lanthanide(III)-based shift reagents in determining the chemical shift of the intraliposomal water protons, which is a relevant factor for generating the CEST contrast. It is demonstrated that a highly shifted resonance for the encapsulated water can be attained by increasing the percentage of the amphiphilic shift reagent incorporated in the liposome bilayer. It is also demonstrated that the shift contribution arising from the bulk magnetic susceptibility can be optimized through the modulation of the osmotic shrinkage. In terms of sensitivity, it is shown that the saturation transfer efficiency can be significantly improved by increasing the size of the vesicle, thus allowing a high number of exchangeable protons to be saturated. In addition, the role played by the intensity of the saturating radiofrequency field has also been highlighted.