Enhancement of Contrast in Magnetic Resonance Images by Paramagnetic Agents: Possibilities and Problems

Abstract

Despite the beauty and excellent spatial resolution of magnetic resonance images of native tissue, the improvement in contrast achievable by the introduction of exogenous paramagnetic agents often more than offsets the toxicity risks, and several such agents are currently in clinical trials. The efficacy of any agent relates to the changes it induces in tissue relaxation rates per unit concentration of agent (its relaxivity), which in turn — as is well known—depends both on magnetic field strength and on the physical and chemical environment of the agent. The latter depends on in vivo biochemistry, and may vary from one tissue to another. In addition, current imaging (including animal studies) is done in the range 0.2–200 MHz proton Larmor frequency and, at the highest fields, water and lipid protons can be distinguished and imaged separately. Thus there is much to consider, several classes of problems and related paramagnetic agents exist: (1) Agents that remain in the intact circulation until excreted through the kidney. These include small chelate complexes of Fe3+ and Gd3+ as well as conjugates, both covalent and hydrophobic, with plasma proteins, generally albumin or immunoglobulins. (2) Agents that are scavenged by the liver, ultimately to be excreted, via the bile and gall bladder, into the intestine. There is a search now for safe agents of this class, which is complicated by liver biochemistry that can release the metal ions and increase toxicity. (3) It has been discovered that some non S‐state ions, usually regarded as shifters rather than relaxers, can have high relaxivities at high fields, in part because of directed orbitals. Mn3+‐porphyrin is an example. (4) Aggregates and particulates of magnetic material are becoming popular, in part because they influence 1/T2 preferentially at imaging fields, and in part because their fate in vivo is rather benign. (5) Lipophilic agents, such as nitroxide free radicals, may enhance the relaxation rates of adipose tissue preferentially. It has recently been shown that neat triolein is a good model for such tissue, providing a sizable area for new investigations. (6) Nuclei other than protons may be important, perhaps the most interesting being fluorine because of its presence in synthetic blood substitutes. We present an overview of our recent collaborative work in these many areas, results now under the rubric of “relaxometry”. This work is made possible because of continued advances in the specialized instrumentation (“field‐cycling relaxometers”) required for such investigations. Copyright © 1988 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim