Gadolinium-based contrast agents

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Molecular complexes containing the rare earth metal gadolinium, chelated to a carrier ligand, form the gadolinium contrast agents (a type of paramagnetic contrast agent) which are the primary class of MRI contrast media. The intravenous route of administration is the commonest.

Chemistry

The gadolinium ion is useful as an MRI contrast agent because it has seven unpaired electrons, which is the greatest number of unpaired electron spins possible for an atom.

Gadolinium molecules shorten the spin-lattice relaxation time (T1) of voxels in which they are present. As a result, on T1-weighted images they have a brighter signal. This can have a number of uses:

Note

  • IV contrast is not required for all MR angiography, MR venography and MR perfusion sequences
  • some of the MRI contrast media employ other chemical elements than gadolinium, e.g. iron, manganese
    • Mechanism of enhancement

    Tissue that demonstrates enhancement following administration of gadolinium-containing IV contrast does so because of a combination of the following two mechanisms :

  • intravascular enhancement
  • interstitial enhancement

    • Which one of these dominates depends on the characteristics of the tissue.

    Effect on T2 relaxation time

    Gadolinium shortens T2 relaxation time and actually results in a hypointense signal, indeed at very high concentrations of gadolinium contrast media a signal void may appear to be present.

    Excretion 

    Most gadolinium contrast agents are excreted through the renal system and therefore have a prolonged half-life in renal failure.

    Adverse reactions

    Allergic reactions to gadolinium-based contrast agents are relatively rare, occurring in 0.04-0.3% of administrations, of which 0.4-9% are severe . These adverse reactions can be acute or chronic.

    There is 30% possibility in recurrence of hypersensitivity in patients those who known to have a previous hypersensitivity episode to gadolinium based contrast media . The risk if adverse reactions are higher in patients with bronchial asthma, known allergy to iodine based contrast media or others.

    There is an association between the use of gadolinium-based contrast agents in patients with renal failure and nephrogenic systemic fibrosis (NSF). Consequently, gadolinium-based contrast agents are contraindicated for patients who have acute kidney injury or severe chronic kidney disease (such as glomerular filtration rate <30 mL/min) .

    Gadolinium deposits in trace amounts in various organs, especially the brain (e.g. dentate nucleus of the cerebellum, globus pallidus) following administration of gadolinium-based contrast agents. The clinical significance of gadolinium deposition is heretofore unknown .

    Macrocyclic agents have less chemical instability than linear agents, resulting in a lower risk of nephrogenic systemic fibrosis and lower gadolinium deposition. On the other hand, cyclic agents have been associated with a higher risk of allergic reactions.

    The ACR has divided gadolinium contrast agents into 3 groups depending on the risk of NSF .

    Specific agents

    The gadolinium contrast agents can be divided into according to whether A) the carrier ligand is linear or macrocyclic and B) whether they are ionic or non-ionic, leading to four groupings.