Studies of factors affecting the design of NMR contrast agents: manganese in blood as a model system

Some factors affecting the performance of paramagnetic ions as contrast agents for proton NMR imaging have been studied. It is demonstrated that the relaxation rate of an aqueous solution of the ion is not reliably predicted by its magnetic moment, but that significant relaxation enhancement may result when the ion is complexed with large molecules, which increases the dominant correlation time. This enhancement in turn can be altered by factors such as pH and competition for binding. Chelation of the paramagnetic ion, which may be implemented to lower its toxicity, can considerably reduce its efficacy by not only limiting its access to water but also by preventing the enhancement from associations and macromolecules. For manganese the ratio T₁/T₂ is a useful parameter which is sensitive to the degree of metal binding. These features of paramagnetic relaxation enhancement in tissue are demonstrated in a series of experiments on systems consisting of blood components and manganese.