MRI CONTRAST AGENT

 

MRI CONTRAST AGENT

What is gadolinium used for?

Gadolinium-based contrast agents (GBCAs) help doctors see abnormal tissues in magnetic resonance imaging (MRI) scans with more detail. They help doctors diagnose inflammation, tumors and blood clots by providing them with clearer, brighter images from inside the body.

What are the possible side effects of gadolinium?

Gadolinium may cause side effects in some people but these are usually mild and short lasting. Some of the more common side effects include: injection site pain • nausea • vomiting • itching • rash • headache • parasthesia (abnormal skin sensation, such as prickling, burning or tingling).

Which gadolinium is safest?

Over the last three decades, gadolinium contrast injections have successfully been used in hundreds of millions of patients. It's safe, not radioactive and is different (and better) than the contrast agents used for a CT scan. The U.S. Food and Drug Administration has approved Dotarem as safe for use in MRI scans.

Is gadolinium a heavy metal?

Gadolinium is the element employed as the basis of GBCAs, which have been widely used as MRI contrast agents for nearly three decades. "However, it is also a toxic heavy metal that is not a normal trace element in the body,

Is gadolinium bad for kidneys?

Gadolinium-containing contrast agents may increase the risk of a rare but serious disease called nephrogenic systemic fibrosis in people with severe kidney failure. Nephrogenic systemic fibrosis triggers thickening of the skin, organs and other tissues.

How long does gadolinium stay in the body?

With normal kidney function, most of the gadolinium is removed from your body in the urine within 24 hours. If you have acute renal failure or severe chronic kidney disease and receive a gadolinium-based contrast agent, there may be a very small risk of developing a rare condition.

Should you drink a lot of water after MRI with contrast?

It is very important to drink plenty of water before and after the contrast injection. Staying well hydrated helps the technician get the needle in your vein painlessly. It also helps flush out the Gadolinium after the procedure is over.

Intravenous MRI contrast agents

Intravenous MRI contrast agents include chelates of paramagnetic ions, both ionic and non-ionic. The particulates, sequestered in the liver, spleen, and lymph nodes, the intravascular agents, confined to the blood pool, and tumour specific agents are discusses separately (see bottom). 

NOTE: This article has been transferred from mritutor.org and was last updated in March 5, 1996. Review and edit pending. 

Paramagnetic metal ions suitable as MRI contrast agents are all potentially toxic when injected IV at or near doses needed for clinical imaging. With chelation of these ions, acute toxicity is reduced and elimination rate is increased thereby reducing the chance of long term toxicity.

Ionics

Chelates of paramagnetic ions Cr and Gd with EDTA were first used however EDTA was of relatively low stability resulting in toxicity in animals 1. Chelates with a higher stability constant have since been used successfully such as Gd-DTPA.

Gd-DTPA was the first intravenous MR contrast agent to be approved for human use (Magnevist, Berlex Labs). Gd has a large magnetic moment, exceeded only by Dysprosium(III) and Holmium(III), explaining its paramagnetic properties at low concentrations. This large magnetic moment is related to its seven unpaired orbital electrons. Gd-DTPA has similar pharmacokinetics as iodinated contrast agents. It is distributed in the intravascular and extracellular fluid spaces, does not cross an intact blood-brain-barrier, and is excreted rapidly by glomerular filtration 2.

Non-ionics

The development of non-ionic contrast agents for MRI has parallelled that for iodinated contrast materials. Ionic chelates are also hyperosmolar and some of their side effects may be attributed to this property.

Gadodiamide

Gadodiamide (Omniscan, Winthrop Pharm.) is a non-ionic complex with two-fifths of the osmolality of Gd-DTPA. It has a median lethal dose of 34 mmol/kg resulting in a safety ratio of 2-3 times that of Gd-DOTA, and 3-4 times that of Gd-DTPA. No abnormal serum bilirubin levels occur, however elevated serum iron levels occurred with an incidence of 8.2% in one study of 73 patients.The efficacy of this contrast is similar to that of Gd-DTPA 3.

Gadoteridol 

Gadoteridol (Prohance, Squibb) was the third intravenous contrast agent on the market. It is a low osmolar, non-ionic contrast as is gadodiamide. Indications for use and efficacy are similar to the other agents 4.

MRI contrast agent safety

Though considered safer than the frequently used iodinated contrast agents used in x-ray and CT studies, there are safety issues with MRI contrast agents as well. Paramagnetic metal ions suitable as MRI contrast agents are all potentially toxic when injected IV at or near doses needed for clinical imaging. With chelation of these ions, acute toxicity is reduced and elimination rate is increased, thereby reducing the chance of long-term toxicity.

The most commonly reported reactions associated with the injection of Gd-DTPA are

headache (6.5%)

injection site coldness (3.6%)

injection site pain or burning (2.5%)

nausea (1.9%)

Recent adverse rates for Gd-DTPA are lower than this and comparable to those of gadodiamide and gadoteridol (1.4%-3% for headache, nausea, and dizziness; <1% for the others). The safety factor or ratio (ratio of the LD50 to the imaging dose) may be used to assess the relative acute toxicity of contrast agents. The elimination half-life for the Gd-containing contrast agents range from 1.25-1.6 hours.

Reports of several episodes of severe anaphylactoid reactions after IV injection of Gd-DTPA are published. The frequency of these reactions is about 1 in 100,000 doses. Potential risk factors may include a history of asthma and significant reaction to previously administered iodinated contrast material. It is suggested that the threshold for injecting gadolinium be raised, in those patients, based on an individual risk/benefit ratio. Prophylactic pharmacotherapy with antihistamines and corticosteroids, such as Greenberger's protocol, is suggested for high-risk patients prior to contrast injections 2.

Effect on serum laboratory values

Gadolinium-containing contrast agents usually have no effect on blood chemistries and haematologic studies except transient elevation of serum iron and bilirubin levels. These elevations peaked at 4 to 6 hours post-injection and returned to baseline values in 24 to 48 hours. The mechanism of these elevations is uncertain but may be related to mild haemolysis. A 10-11% increase in the activated partial thromboplastin time and thrombin time occurs in vitro with inhibition of platelet aggregation. The platelet aggregation inhibition is less than that seen with iodinated ionic contrast material and no bleeding problems are reported clinically. 

Effect on physiology

Transient and mild drop blood pressure is reported in both animals and humans. A study of 1,068 patients reported hypotension in 0.3% of the subjects and other symptoms such as syncope probably associated with hypotension in 0.8%. Most of these symptoms occurred 25-85 minutes after the injection.

Deoxygenated sickle erythrocytes align perpendicular to a magnetic field in vitro studies raising the possibility of occlusive complications in patients with sickle cell anaemia. No clinical reports of this potential problem have been found 1. 

Retained gadolinium

There are reports that repeated administrations of IV gadolinium contrast leads to T1 shortening in the dentate nuclei, and possibly the globus pallidus 3. This is thought to be related to retained gadolinium contrast at these sites. The effect is thought to be more common with linear gadolinium chelates rather than with cyclic chelates 4,5. Gadolinium is deposited in the brain in patients with normal renal function 3. Gadolinium retention is not considered to be related to radiation therapy in patients receiving multiple studies for head and neck cancer 6. The clinical effect of this deposition, if any, is currently unknown. However, the phenomenon is currently under investigation by the FDA .