The paramagnetic water-soluble metallofullerenes (Gd-fullerenols), which have strong T1 shortening effect, can be used as a novel core material of MRI contrast agents. Gadolinium endohedral metallofullerenes have been synthesized as polyhydroxyl forms (Gd@C82(OH)n, Gd-fullerenes) with the evaluation of their paramagnetic properties. The modification to the water-soluble forms is essential for the biomedical application of the metallofullerenes. The in vitro water proton relaxivity, R1 (the effect on 1/T1), of Gd-fullerenes is significantly higher (20-folds) than that of commercial MRI contrast agents - e.g. Gd-DTPA.

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.

OptiMARK® is a formulation of a nonionic gadolinium chelate of diethylenetriamine pentaacetic acid bismethoxyethylamide (gadoversetamide), for use as a paramagnetic MRI contrast agent. OptiMARK® (gadoversetamide injection) is to be administered by intravenous injection. OptiMARK® is indicated for MRI diagnostic procedures to provide increased enhancement and visualization of lesions of the brain, spine and liver, including tumors.

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.

Types of oral contrast agents with positive signal enhancement:
Ideal oral contrast agents are immiscible with water, biologically inert, have a low viscosity and surface tension. Oral positive contrast agents may improve the separation of bowel loops, the detection of polyps in colon MRI or the assessment of inflammatory bowel in the small intestine. Several positive oral contrast agents are available and they are safe to use, for example gadolinium solution, ferric ammonium citrate, different oil emulsions and pediatric formula.
Unfavorably motion artifacts caused by respiration and peristalsis may be increased in MR imaging. In addition, the signal of the positive contrast medium may decrease caused by dilution in gastrointestinal (GI) secretions. With the use of contrast agents that are immiscible with water, no dilution and accompanying signal loss occur even when the contrast agent is in contact with the intraluminal contents of the GI tract. Another disadvantage may be residual substances in the bowel, resembling masses when enclosed by bright signal. In addition, positive contrast agents may have a similar signal as bright masses, which make their (e.g. lipoma) detection difficult.

See also Gastrointestinal Paramagnetic Contrast Agents, Combination Oral Contrast Agents, Gastrointestinal Diamagnetic Contrast Agents.

Liver imaging with gadolinium contrast enhanced MRI is sometimes not sufficient for a reliable diagnosis of liver lesions. For this reasons, special liver Contrast agents that are targeted to the reticuloendothelial system (RES), have been developed to improve both detection and characterization of liver and spleen lesions. Reticuloendothelial Contrast Agents, as e.g. superparamagnetic iron oxides (SPIO), are taken up by healthy liver tissue but not tumors.
These RES targeted contrast agents provide a prolonged imaging window and enough time for high spatial resolution or multiple breath hold images. Reticuloendothelial contrast agents have an increased sensitivity for the detection of small liver lesions (e.g., metastases), compared with gadolinium enhanced MRI and spiral CT. At higher field strengths with an increased signal to noise ratio the susceptibility effect with iron oxide particles may be enhanced.
Other new agents (Gadobenate Dimeglumine, Gadoxetic Acid) have both an initial extracellular circulation and a delayed liver-specific uptake. Since a considerable part of these contrast agents is excreted in the bile, functional biliary imaging can diagnose biliary anomalies, postoperative bile leaks, and anastomotic strictures. Other agents, such as liposomes (with encapsulated Gd-DTPA) or DOTA complexes are in different development stages.

See also Hepatobiliary Contrast Agents, Gadolinium Oxide, Superparamagnetic Iron Oxide and Liposomes.