How safe are Gd-based MR contrast agentsIntroduced byAbdulrahman AlquaitMedical imaging MSc student

-What is a contrast agent? It is a substance which is put into the body with the intention of increasing the image contrast between two tissues, or between a tissue and an abnormal region within it. 

How can we enhance image contrast in MRI?

The parameters most commonly used to provide image contrast are:

• Proton density.• T1 relaxation time.• T2 relaxation time.

Most contrast agents achieve their effect by changing the relaxation times of water protons in tissue.

How? Dipole-dipole interaction between the

water protons and those of the “relaxing agent” results in an increased relaxation rate given by:

= gyromagnetic ratio of water protons. gyromagnetic ratio of relaxing agent. r = separation between water protons and relaxing agent protons.

What is an ideal contrast gent ? A good relaxing agent should have a

large value for (). The electron is highly effective since its

gyromagnetic ratio is 600 times that of the proton.

In general, electrons occur in pairs round their nuclei and give no net magnetic moment.

Substances with unpaired electrons are ideal for our purpose.

Why Gadolinium? -What is Gadolinium A sample of gadolinium

-A paramagnetic substance.

-atomic number of 64. -7 unpaired electrons

(large magnetic moment).

-TOXIC .

Gd- based contrast agent chelates .

To reduce their toxicity they have to be bound in chelates.

chelates are complexes with at least two bonds (e.g. DTPA, DOTA).

Chelates has to be very stable so virtually no free ion is released inside the body.

Chelates must have short half-life (2 hours) to be excreted from the body.

Gd- based contrast agents contra indications Allergy . Pregnancy (assessed according to the risk/benefit ratio).

Adverse effects Nausea, headache, taste alteration. Nephrogenic Systemic Fibrosis (NSF).

NSF also known as nephrogenic fibrosing

dermopathy (NFD), is a rare condition that involves fibrosis of the skin and connective tissues, which can lead to contractures and joint immobility.

NSF usually starts in the extremities, sometimes involving the trunk, and other organs can become affected later including the lungs, liver, muscles, and heart, in some cases leading to a fatal outcome.

Only occurred in patients with renal dysfunction.

NSF

NSF MECHANISM The mechanism by which some gadolinium-

containing contrast agents might trigger NSF is under investigation.

Patients with severe renal impairment have an increased risk of NSF because they take longer to eliminate the contrast agent from the body compared with those without renal impairment.

Gadolinium ions (Gd3+) may be released into the body from a chelate complex of the gadolinium-containing contrast agent by transmetallation with ions from the body (e.g. zinc, iron, calcium, magnesium).

Free Gd3+ can accumulate in tissues and organs and trigger fibrosis, leading to NSF.

Brand name Generic name

Chemical structure Charge Elimination

pathwayProtein binding

Cases of NSF

Omniscan gadodiamide Linear Non-ionic Kidney None Yes

OptiMARK gadoversetamide Linear Non-ionic Kidney None Yes

Magnevist gadopentetic acid Linear Ionic Kidney None Yes

MultiHance Gadobenic acid Linear Ionic 97% Kidney,

3% Bile<5% Yes

Primovist gadoxetic acid Linear Ionic 50% Kidney,

50% Bile<15% No

Vasovist gadofosveset Linear Ionic 91% Kidney, 9% Bile

>85% No

ProHance gadoteridol Cyclic Non-ionic Kidney None NoGadovist gadobutrol Cyclic Non-ionic Kidney None No

Dotarem Gadoteric acid Cyclic Ionic Kidney None No

Eight gadolinium-containing contrast agents are currently authorized in the UK:

New advice to minimise the risk of NSF by MHRA*

On the basis of current evidence, the risk classification is as follows:

• High risk, -Omniscan, OptiMARK and Magnevist.

• Medium risk,

-MultiHance, Primovist and Vasovist.

• Low risk,-Gadovist, ProHance and Dotarem.

* Medicines and Healthcare products Regulatory Agency (Jan 2010) .

Risk-minimization measures considered by MHRA for Gd-based contrast agents:

Renal-function monitoring. Renal impairment. Perioperative liver-transplantation period. Neonates. Infants. Breastfeeding. Pregnancy. Haemodialysis. Recording of the agent used. Reporting of suspected adverse reactions.

Conclusion Millions of Gd- based contrast agents are performed

world wide. As of March 2010, more than 335 cases of NSF have

been identified according to the Yale NSF Registry. NSF has occurred only in people with kidney disease. NSF affects males and females and has been confirmed

in children and the elderly. It has been identified in patients from a variety of ethnic

backgrounds from North and South America, Europe, Asia and Australia.

Two U.S. universities were able to eliminate cases of NSF among their patients receiving MRI scans by switching to a different gadolinium-based contrast agent and by adopting stricter guidelines for contrast use.

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