Gadovist® is an extracellular, neutral macrocyclic (gadolinium (Gd) complex) MRI contrast agents for central nervous system indications, particularly suited for studies in which high doses are required or advantageous. Gadovist® (also Gadograf) was available in two concentrations, currently only Gadovist® 1.0 is marketed.
The product was approved in Switzerland in 1999 and in Germany in 2000. Gadovist® 1.0 is in USA currently in the drug development and approval process, particularly for magnetic resonance angiography.

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.

See also Paramagnetic Contrast Agents and Gadobutrol.

Liver imaging can be performed with sonography, computed tomography (CT) and magnetic resonance imaging (MRI). Ultrasound is, caused by the easy access, still the first-line imaging method of choice; CT and MRI are applied whenever ultrasound imaging yields vague results. Indications are the characterization of metastases and primary liver tumors e.g., benign lesions such as focal nodular hyperplasia (FNH), adenoma, hemangioma and malignant lesions (cancer) such as hepatocellular carcinomas (HCC). The decision, which medical imaging modality is more suitable, MRI or CT, is dependent on the different factors. CT is less costly and more widely available; modern multislice scanners provide high spatial resolution and short scan times but has the disadvantage of radiation exposure.
With the introduction of high performance MR systems and advanced sequences the image quality of MRI for the liver has gained substantially. Fast spin echo or single shot techniques, often combined with fat suppression, are the most common T2 weighted sequences used in liver MRI procedures. Spoiled gradient echo sequences are used as ideal T1 weighted sequences for evaluating of the liver. The repetition time (TR) can be sufficiently long to acquire enough sections covering the entire liver in one pass, and to provide good signal to noise. The TE should be the shortest in phase echo time (TE), which provides strong T1 weighting, minimizes magnetic susceptibility effects, and permits acquisition within one breath hold to cover the whole liver. A flip angle of 80° provides good T1 weighting and less of power deposition and tissue saturation than a larger flip angle that would provide comparable T1 weighting.
Liver MRI is very dependent on the administration of contrast agents, especially when detection and characterization of focal lesions are the issues. Liver MRI combined with MRCP is useful to evaluate patients with hepatic and biliary disease.
Gadolinium chelates are typical non-specific extracellular agents diffusing rapidly to the extravascular space of tissues being cleared by glomerular filtration at the kidney. These characteristics are somewhat problematic when a large organ with a huge interstitial space like the liver is imaged. These agents provide a small temporal imaging window (seconds), after which they begin to diffuse to the interstitial space not only of healthy liver cells but also of lesions, reducing the contrast gradient necessary for easy lesion detection. Dynamic MRI with multiple phases after i.v. contrast media (Gd chelates), with arterial, portal and late phase images (similar to CT) provides additional information.
An additional advantage of MRI is the availability of liver-specific contrast agents (see also Hepatobiliary Contrast Agents). Gd-EOB-DTPA (gadoxetate disodium, Gadolinium ethoxybenzyl dimeglumine, EOVIST Injection, brand name in other countries is Primovist) is a gadolinium-based MRI contrast agent approved by the FDA for the detection and characterization of known or suspected focal liver lesions.
Gd-EOB-DTPA provides dynamic phases after intravenous injection, similarly to non-specific gadolinium chelates, and distributes into the hepatocytes and bile ducts during the hepatobiliary phase. It has up to 50% hepatobiliary excretion in the normal liver.
Since ferumoxides are not eliminated by the kidney, they possess long plasmatic half-lives, allowing circulation for several minutes in the vascular space. The uptake process is dependent on the total size of the particle being quicker for larger particles with a size of the range of 150 nm (called superparamagnetic iron oxide). The smaller ones, possessing a total particle size in the order of 30 nm, are called ultrasmall superparamagnetic iron oxide particles and they suffer a slower uptake by RES cells. Intracellular contrast agents used in liver MRI are primarily targeted to the normal liver parenchyma and not to pathological cells. Currently, iron oxide based MRI contrast agents are not marketed.
Beyond contrast enhanced MRI, the detection of fatty liver disease and iron overload has clinical significance due to the potential for evolution into cirrhosis and hepatocellular carcinoma. Imaging-based liver fat quantification (see also Dixon) provides noninvasively information about fat metabolism; chemical shift imaging or T2*-weighted imaging allow the quantification of hepatic iron concentration.

See also Abdominal Imaging, Primovistâ„¢, Liver Acquisition with Volume Acquisition (LAVA), T1W High Resolution Isotropic Volume Examination (THRIVE) and Bolus Injection.

For Ultrasound Imaging (USI) see Liver Sonography at Medical-Ultrasound-Imaging.com.

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.

Primovist™ (U.S brand name Eovist®) is a highly specific MRI contrast agent for the imaging, detection and characterization of liver conditions, including liver tumors, cysts, as well as other malignant and benign lesions. It is a water-soluble ethoxybenzyl derivative of Gd-DTPA. This compound is taken up by the hepatocytes (approximately 30% of the dose goes to the hepatocytes) and is equally excreted renal and biliary in humans.
Primovist™ brightens the signal of T1 weighted MR images immediately after contrast administration. Dynamic scanning and imaging of the accumulation phase (best after 20 min.) can also be performed after bolus injection of Primovistâ„¢. The hepatocytes uptake will increase the signal intensity of normal liver parenchyma. This results in improved lesion-to-liver contrast because malignant tumors (metastases, the majority of hepatocellular carcinomas) do not contain either hepatocytes or their functioning is hampered.

WARNING: 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.

Vasovistâ„¢ is an albumin-targeted intravascular contrast agent. It is indicated for contrast enhanced MR angiography (CE-MRA) for the visualization of abdominal or limb vessels in patients with suspected or known vascular disease. After IV injection, Vasovistâ„¢ binds reversibly to human albumin in plasma, which results in long-lasting increased relaxivity. Imaging from 5 to 50 min is possible. A small unbound portion is, by glomerular filtration, eliminated by the kidneys.
AngioMARK® was the formerly trade name and MS-325 the research name. Currently the phase III clinical trials are completed to determine its efficacy for peripheral vascular disease and coronary artery disease.
In the U.S., EPIX received an approvable letter from the U.S. Food and Drug Administration (FDA) for Vasovistâ„¢ in January 2005. In 2009, Epix Pharmaceuticals has sold the U.S., Canadian and Australian rights for its blood pool agent (now named ABLAVARâ„¢), to Lantheus Medical Imaging, Inc..

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 the liver transplantation period.

See also MRI Safety.