On Water and its Effect on the Performance of T1-Shortening Contrast Agents

The performance of low molecular weight Gd³⁺ chelates as T₁-shortening contrast agents for MRI is limited by their rapid rate of molecular tumbling, which makes them very sensitive to factors that alter the rate of molecular reorientation. Unlike the interactions of these chelates with other solutes present in solution, which have been widely studied, the effect of the solvent water itself on tumbling seems to have been largely ignored. Water has long been known to adopt structures that vary from freely diffusing molecules on one extreme and a more “ice-like” structure on the other. A variety of salts can be used to alter this “structure” of water. Relaxometric studies on inner and outersphere Gd³⁺ chelates were performed in the presence of both structure making and structure breaking salts. The addition of structure-making salts to low molecular weight Gd³⁺ chelates was found to increase both the second- and outer-sphere contributions to relaxivity. These results point to a slowing of molecular tumbling arising from an increase solvent structure and therefore microviscosity. The implication of these findings is that the performance of low molecular weight Gd³⁺ contrast agents is not, as generally assumed, constant in the absence of secondary interactions but may vary depending upon the nature of the solution in which it is dissolved.     

Liposomes Loaded with Hydrophobic Iron Oxide Nanoparticles: Suitable T2 Contrast Agents for MRI

There has been a recent surge of interest in the use of superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents (CAs) for magnetic resonance imaging (MRI), due to their tunable properties and their low toxicity compared with other CAs such as gadolinium. SPIONs exert a strong influence on spin-spin T₂ relaxation times by decreasing the MR signal in the regions to which they are delivered, consequently yielding darker images or negative contrast. Given the potential of these nanoparticles to enhance detection of alterations in soft tissues, we studied the MRI response of hydrophobic or hydrophilic SPIONs loaded into liposomes (magnetoliposomes) of different lipid composition obtained by sonication. These hybrid nanostructures were characterized by measuring several parameters such as size and polydispersity, and number of SPIONs encapsulated or embedded into the lipid systems. We then studied the influence of acyl chain length as well as its unsaturation, charge, and presence of cholesterol in the lipid bilayer at high field strength (7 T) to mimic the conditions used in preclinical assays. Our results showed a high variability depending on the nature of the magnetic particles. Focusing on the hydrophobic SPIONs, the cholesterol-containing samples showed a slight reduction in r₂, while unsaturation of the lipid acyl chain and inclusion of a negatively charged lipid into the bilayer appeared to yield a marked increase in negative contrast, thus rendering these magnetoliposomes suitable candidates as CAs, especially as a liver CA.