Contrast agents are chemical substances introduced to the anatomical or functional region being imaged, to increase the differences between different tissues or between normal and abnormal tissue, by altering the relaxation times. MRI contrast agents are classified by the different changes in relaxation times after their injection.
The design objectives for the next generation of MR contrast agents will likely focus on prolonging intravascular retention, improving tissue targeting, and accessing new contrast mechanisms. Macromolecular paramagnetic contrast agents are being tested worldwide. Preclinical data shows that these agents demonstrate great promise for improving the quality of MR angiography, and in quantificating capillary permeability and myocardial perfusion.
Ultrasmall superparamagnetic iron oxide (USPIO) particles have been evaluated in multicenter clinical trials for lymph node MR imaging and MR angiography, with the clinical impact under discussion. In addition, a wide variety of vector and carrier molecules, including antibodies, peptides, proteins, polysaccharides, liposomes, and cells have been developed to deliver magnetic labels to specific sites. Technical advances in MR imaging will further increase the efficacy and necessity of tissue-specific MRI contrast agents.

See also Adverse Reaction and Nephrogenic Systemic Fibrosis.

See also the related poll result: 'The development of contrast agents in MRI is'

Gastrointestinal (GI) superparamagnetic contrast agents are used in MRI to improve the visualization of e.g., the intestinal tract, the pancreas (see MRCP), etc. Disadvantages are susceptibility artifacts e.g., dependent on delayed imaging or large volumes resulting in artifacts in the colon and distal small bowel loops related to higher concentration of the particles and absorption of the fluid.
Different types of MRI gastrointestinal superparamagnetic contrast agents:
Usually gastrointestinal superparamagnetic contrast media consist of small iron oxide crystals (ferrites), which produce a signal reduction in the stomach and bowel after oral administration. The T2 shortening caused by these particles is produced from the local magnetic field inhomogeneities associated with the large magnetic moments of superparamagnetic particles. Ferrites are iron oxides of the general formula Fe203.MO, where M is a divalent metal ion and may be mixed with Fe3O4 in different preparations. Ferrites can produce symptoms of nausea after oral administration, as well as flatulence and a transient rise in serum iron. Embedding in inert substances reduce side effects by decreasing the absorption and interaction with body tissues. Combining these contrast materials with polymers such as polyethylene glycol or cellulose, or with sugars such as dextrose, results in improved T1 and/or T2 relaxivity compared with that of the contrast agent alone.

See also Negative Oral Contrast Agents, Gastrointestinal Diamagnetic Contrast Agents, Relaxivity, and Combination Oral Contrast Agents.

MultiHance® is a paramagnetic contrast agent for use in diagnostic magnetic resonance imaging (MRI) of the liver and central nervous system. MultiHance® is a small molecular weight chelate, which tightly binds the Gd atom. The substance is excreted partly by the kidneys, partly by the biliary system, which is especially unique.
MultiHance® is indicated, for the detection of focal liver lesions in patients with known or suspected primary liver cancer (e.g. hepatocellular carcinoma) or metastatic disease.
MultiHance® is also indicated in brain MRI and spine MRI where it improves the detection of lesions and provides diagnostic information additional to that obtained with unenhanced MRI.
Gd-BOPTA-enhanced MRA can provide superior vascular signal intensity and SNR, as compared with Gd-DTPA, due to its higher relaxivity, even at lower doses.
1 ml of solution MultiHance® contains: (0.5M) gadobenate dimeglumine 529 mg = gadobenic acid 334 mg + meglumine 195 mg. Viscosity at 37°C: 5.3 mPa

WARNING: NEPHROGENIC SYSTEMIC FIBROSIS Gadolinium-based contrast agents increase the risk for nephrogenic systemic fibrosis (NSF) in patients with acute or chronic severe renal insufficiency (glomerular filtration rate less than 30 mL/min/1.73m²), or acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period.

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.

Short name: Gd-BOPTA, generic name: Gadobenate dimeglumine
A paramagnetic MRI contrast agent (small molecular weight Gd-chelate) with 0.5 and 0.25 molar concentration.
The albumin-mediated relaxation enhancement may result in advantages for Gd-BOPTA over Gd-DTPA and other gadolinium agents in poorly vascularized, small, or lesions with low enhancement and in tumors with high concentrations of albumin. The substance is excreted partly by the kidneys (75-90%), partly by the biliary system (10-25%). The uptake in the liver is about 5% in humans. It is bolus injectable.

See Contrast Agents and MultiHance®.