The main problem with paramagnetic heavy metal ions in their native form is their toxicity. Complexation of the metal ion with organic ligand, while considerably decreasing toxicity, may alter paramagnetic properties of the metal. Chromium-EDTA complex was the first such agent tried, but problems with synthesis and long-term stability prevented its clinical application.

(CE MRA) Contrast enhanced MR angiography is based on the T1 values of blood, the surrounding tissue, and paramagnetic contrast agent.
T1-shortening contrast agents reduces the T1 value of the blood (approximately to 50 msec, shorter than that of the surrounding tissues) and allow the visualization of blood vessels, as the images are no longer dependent primarily on the inflow effect of the blood. Contrast enhanced MRA is performed with a short TR to have low signal (due to the longer T1) from the stationary tissue, short scan time to facilitate breath hold imaging, short TE to minimize T2* effects and a bolus injection of a sufficient dose of a gadolinium chelate.
Images of the region of interest are performed with 3D spoiled gradient echo pulse sequences. The enhancement is maximized by timing the contrast agent injection such that the period of maximum arterial concentration corresponds to the k-space acquisition. Different techniques are used to ensure optimal contrast of the arteries e.g., bolus timing, automatic bolus detection, bolus tracking, care bolus. A high resolution with near isotropic voxels and minimal pulsatility and misregistration artifacts should be striven for. The postprocessing with the maximum intensity projection (MIP) enables different views of the 3D data set.
Unlike conventional MRA techniques based on velocity dependent inflow or phase shift techniques, contrast enhanced MRA exploits the gadolinium induced T1-shortening effects. CE MRA reduces or eliminates most of the artifacts of time of flight angiography or phase contrast angiography. Advantages are the possibility of in plane imaging of the blood vessels, which allows to examine large parts in a short time and high resolution scans in one breath hold. CE MRA has found a wide acceptance in the clinical routine, caused by the advantages:

Cr-HIDA (Chromium diethyl HIDA meglumine) is a substance with paramagnetic characteristics that has been tested in animals for the use as a hepatobiliary MRI contrast agent.

See also Hepatobiliary Contrast Agents, Paramagnetic Substance, Paramagnetism.

Ferrioxamines are potential iron oxide-based intravascular contrast agents. Ferrioxamine methanesulfonate, ferrioxamine-B, and hydroxyethyl-starch-ferrioxamine have been tested as MRI contrast agents, partly in clinical trials.
Ferrioxamine methanesulfonate was tested as a paramagnetic agent for the imaging of the kidney and the urogenital system. Hydroxyethyl-starch-ferrioxamine has the potential to provide information regarding myocardial vascular flow and ferrioxamine-B derivatives may be used as hepatobiliary contrast agents.

See also Superparamagnetic Iron Oxide, Hepatobiliary Contrast Agents.

Short name: Ami 227, generic name: Ferumoxtran, (USPIO)
Ferumoxtran is a substance of the class of ultrasmall superparamagnetic iron oxide used as a lymph node specific contrast agent for MRI.
See also Combidex®, Sinerem® and Ultrasmall Superparamagnetic Iron Oxide.
Partner(s): Cytogen Corporation, National Cancer Institute. An approvable letter was received from the U.S. Food and Drug Administration for Combidex in June 2000. Advanced Magnetics, Inc. has submitted a complete response to the approvable letter received from the U.S. Food and Drug Administration, which was accepted by the FDA and assigned a user fee goal date of March 30, 2005. In Europe, a Dossier (the European equivalent of a NDA) was submitted by Advanced Magnetics' European partner, Guerbet SA, to the European Medicines Evaluations Agency in December 1999. (Sinerem® is the brand name for this USPIO in Europe manufactured by Guerbet, Combidex® by Advanced Magnetics for the U.S. market)
Advanced Magnetics, Inc. changed its name in July 2007 to AMAG Pharmaceuticals Inc.