IRON-OXIDES AS MR IMAGING CONTRAST AGENTS

THE DEVELOPMENT of contrast agents for magnetic resonance (MR) imaging is to a considerable extent based on observations from early in vitro nuclear MR experiments. It is interesting to note that iron played a key role in spectroscopic studies fundamental to the development of both major classes of MR contrast agents, the T1 agents and the T2 agents. In 1946, Block ct al showed that the T1 of water protons could be shortened by addition of ferric iron (Fe3+) (1,2). Although Fe3+ today has to a great extent been replaced by stronger T1-shortening agents based on gadolinium, this classical experiment was the basis for development of signal-enhancing contrast agents beginning in the late 1970s. Orally administered Fe3+ was the first contrast agent tested in humans and resulted in marked contrast enhancement in the stomach (3). In 1978, nuclear MR studies performed by Ohgushi et al showed that ferromagnetic iron oxide strongly reduced the T2 of gels (4). Although these data were published at the time when Lauterbur et al first suggested the use of paramagnetic compounds for contrast purposes (5), no attention was paid to possible applications of iron oxides as diagnostic agents. At that time, there was a general prejudice against the use of ferromagnetic materials in MR imaging because of field distortion and signal (and information) loss familiar from nuclear MR studies, as well as image artifacts unique to MR imaging. The first MR data showing a possible diagnostic advantage of iron oxides as T2 agents for liver and spleen were presented in 1984 (6). In the last 6-7 years, there has been great interest in developing and testing iron oxide preparations, and the diagnostic potential of different iron oxides has been investigated in numerous experimental studies (7-27). Iron oxide-based preparations for enteral (28-30) and parenteral (31-33) use have also recently been tested in clinical trials. with promising results.