Lawrence R. Muroff, MD, FACR Clinical Professor of Radiology University of Florida and University of South Florida Colleges of Medicine, Tampa

MRI contrast is used for a variety of reasons. Primarily, it is used to improve the detection of disease; that is, to increase sensitivity and diagnostic confidence, to enhance the ability to differentiate normal and abnormal tissue; and to identify the extent of disease. Secondly, and less frequently, it is used to define or characterize disease; to actually make a specific diagnosis. Although there are certain disease entities that have specific or characteristic enhancement patterns, in general, MR contrast is used more for sensitivity than for specificity. Finally, contrast-enhanced MR imaging can be used to demonstrate pathophysiologic activity, including both perfusion and clearance.

There are several types of MR contrast agents being used in clinical practice today. These include not only the extracellular fluid space agents, but also oral agents, extended residence intravascular agents, and organ-specific agents. For the purpose of this publication, we will focus exclusively on the four gadolinium-based extracellular fluid (ECF) agents currently approved for use in the United States (table 1).

Indications and Administration

In general, all of the ECF agents have been approved for use in central nervous system imaging in adults and children. OptiMARK is the only agent not currently approved for use in pediatric patients. Magnevist and ProHance are approved for use in imaging of the head and neck, and there are various approvals for other uses among the different agents as well. To date, none of the agents have FDA approval for use in MR angiography, or cardiovascular or breast imaging. The standard approved clinical dose for each agent is 0.1 mmol/kg of body weight. For some agents, such as ProHance and Omniscan, an additional 0.2 mmol/kg injection may be given to increase sensitivity for detecting poorly enhancing lesions (table 2).

In terms of administration, only the non-ionic agents (Omniscan, ProHance, and OptiMARK) are approved for bolus or rapid injection (table 3). Presently, Magnevist is not approved for a rate greater than 10 mL/15 seconds. None is approved for intraarterial, intraarticular, or intrathecal use at the present time (table 3).

Similarities and Differences

The four gadolinium-based contrast agents have similar biologic properties; they distribute on the basis of blood flow, blood volume, and capillary permeability; there is negligible protein binding; and they are cleared by the kidneys. They have similar physical properties, as well; that is, their ability to shorten T1 is similar.

There are some differences among these agents that need to be considered. One is the issue of net charge; that is, whether an agent is ionic or non-ionic. The other is whether the agent has a linear or a cyclic-type molecular structure (table 4). These two variables result in four possible combinations: an agent can be ionic and have a cyclic structure (no such agent is currently available in the US); ionic and linear (Magnevist); non-ionic and linear (Omniscan and OptiMARK); or non-ionic and cyclic (ProHance).

In terms of safety, all four of the ECF agents have been shown to produce, on occasion, mild adverse reactions, such as nausea and hives. Rarely, moderate reactions have been seen, and very infrequently, anaphylactoid reactions have been reported. These reactions have been seen with all of the agents, and there does not appear to be any significant difference in the reaction rates or types among the agents.

Therefore, in terms of safety and efficacy, I believe it is fair to say that 1 mL of Magnevist equals 1 mL of ProHance equals 1 mL of Omniscan equals 1 mL of OptiMARK.

From a clinical perspective, all of the gadolinium-based ECF agents appear to be identical. This perspective seems to be widely held. In fact, approximately 75% of respondents in the Educational Symposia, Inc., polling said that they consider these agents to be identical in terms on efficacy and safety.

Free Gadolinium

Despite the clinical similarities, on a molecular level, there are several significant structural differences among these agents. As noted above, the major differences are in the net charge (ionic versus non-ionic) and in the ligand (linear versus cyclic). When compared with the linear structure, the cyclic structure, which surrounds the gadolinium ion like a crown, holds the gadolinium far more tightly, resulting in less free gadolinium being released into the body.

Osmolality and Viscosity

Finally, there is the difference between non-ionic and ionic structures. It is well known that the non-ionic agents are less osmolar and less viscous. Such molecular differences may have a significant clinical impact in selected circumstances, such as with the use of power injectors. Furthermore, the issues of extravasation and the use of high-dose procedures may be effected by differences in osmolality and viscosity.

Conclusion

MRI contrast media are used in about a quarter of all MRI procedures. They increase sensitivity and, in some cases, provide a greater specificity of diagnosis. Their use can strengthen diagnostic confidence and impact therapy.

This presentation explores in a general way the similarities and the differences among the agents. Each of these points will be discussed by other authors later in this publication.

Acknowledgment

The author acknowledges with gratitude the work of Val M. Runge, MD, and Mark J. Carvlin, PhD, and the influence this work had on this review article.