Paramagnetic contrast agents in nuclear magnetic resonance medical imaging

Relaxation time differences are the sources of most of the contrast observed in proton NMR images, not only among normal organs and tissues but between lesions and the adjacent tissue. Although these differences are often large, there are low-contrast situations in which it would be desirable to increase the visibility of an organ or region. The study of time-dependent phenomena would also be aided by the ability to change selected relaxation times deliberately. One way to achieve these goals is to administer substances that change proton relaxation times in tissues without causing significant toxic effects or other physiologic changes. Paramagnetic ions and molecules, those with unpaired electrons, may be useful for this purpose because the very large magnetic effects associated with such electrons can drastically decrease water proton relaxation times at concentrations of the order of 100 to 1000 microM, which may be reached in certain organs after doses of 10 to 100 microM/kg. The general characteristics of such paramagnetic substances are described, and specific animal experiments with manganous ion and its complexes, and with stable nitroxide free radicals and molecular oxygen, are reviewed. The paramagnetic contrast agents already studied are effective, and many more are potentially possible, but the most important questions to be answered are whether acute and chronic toxicity are low enough to permit research and diagnosis on humans.