(SPIO) Relatively new types of MRI contrast agents are superparamagnetic iron oxide-based colloids (median diameter greater than 50nm). These compounds consist of nonstoichiometric microcrystalline magnetite cores, which are coated with dextrans (in ferumoxide) or siloxanes (in ferumoxsil). After injection they accumulate in the reticuloendothelial system (RES) of the liver (Kupffer cells) and the spleen. At low doses circulating iron decreases the T1 time of blood, at higher doses predominates the T2* effect.
SPIO agents are much more effective in MR relaxation than paramagnetic agents. Since hepatic tumors either do not contain RES cells or their activity is reduced, the contrast between liver and lesion is improved. Superparamagnetic iron oxides cause noticeable shorter T2 relaxation times with signal loss in the targeted tissue (e.g., liver and spleen) with all standard pulse sequences. Magnetite, a mixture of FeO and Fe2O3, is one of the used iron oxides. FeO can be replaced by Fe3O4.
Use of these colloids as tissue specific contrast agents is now a well-established area of pharmaceutical development. Feridex®, Endorem™, GastroMARK®, Lumirem®, Sinerem®, Resovist® and more patents pending tell us that the last word in this area is not said.
Some remarkable points using SPIO:

See also Superparamagnetism, Superparamagnetic Contrast Agents and Classifications, Characteristics, etc..

(USPIO) The class of the ultrasmall superparamagnetic iron oxide includes several chemically and pharmacologically very distinct materials, which may or may not be interchangeable for a specific use. Some ultrasmall SPIO particles (median diameter less than 50nm) are used as MRI contrast agents (Sinerem®, Combidex®), e.g. to differentiate metastatic from inflammatory lymph nodes. USPIO shows also potential for providing important information about angiogenesis in cancer tumors and could possibly complement MRI helping physicians to identify dangerous arteriosclerosis plaques.
Because of the disadvantageous large T2*//T1 ratio, USPIO compounds are less suitable for arterial bolus contrast enhanced magnetic resonance angiography than gadolinium complexes. The tiny ultrasmall superparamagnetic iron oxides do not accumulate in the RES system as fast as larger particles, which results in a long plasma half-life. USPIO particles, with a small median diameter (less than 10 nm), will accumulate in lymph nodes after an intravenous injection by e.g. direct transcapillary passage through endothelial venules. Once within the nodal parenchyma, phagocytic cells of the mononuclear phagocyte system take up the particles.
As a second way, USPIOs are subsequently taken up from then interstitium by lymphatic vessels and transported to regional lymph nodes. A lymph node with normal phagocytic function takes up a considerable amount and shows a reduction of the signal intensity caused by T2 shortening effects and magnetic susceptibility. Caused by the small uptake of the USPIOs in metastatic lymph nodes, they appear with less signal reduction, and permit the differentiation of healthy lymph nodes from normal-sized, metastatic nodes.

See also Superparamagnetic Contrast Agents, Superparamagnetic Iron Oxide, Very Small Superparamagnetic Iron Oxide Particles, Blood Pool Agents, Intracellular Contrast Agents.

(VSOP) A new class of contrast agents with smaller particle size than SPIO or USPIO with advantages for MR angiography, caused through a longer plasma half-life.

See also Ultrasmall Superparamagnetic Iron Oxide and Superparamagnetic Iron Oxide.

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'

Contrast agent with a preferential intracellular distribution.
Intracellular agents (such as manganese derivatives and ultrasmall superparamagnetic iron oxide), exhibit a flow- and metabolism-dependent uptake. These properties may allow delayed imaging, similar to isotopic methods.
Phospholipid liposomes are rapidly sequestered by the cells in the reticuloendothelial system (RES), primarily in the liver. For imaging of the liver, liposomes may be labeled with MR contrast medium, both positive (T1-shortening) paramagnetic media, and negative (T2-shortening) superparamagnetic media.
Several other nonliposome MR contrast media are also taken up by the RES, e.g.:
Other MR contrast agents accumulate selectively in the hepatocytes, e.g.: