Gadolinium contrast agents

Last revised by Joshua Yap on 3 May 2023

Gadolinium-based contrast media (GBCM)gadolinium-based contrast agents (GBCAs), or simply gadolinium contrast agents, are molecular complexes containing the rare earth metal gadolinium, chelated to a carrier ligand. They are a type of paramagnetic contrast agent, which are the primary class of MRI contrast media. The intravenous route of administration is the most common.

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:

It should be noted that IV contrast is not required for all MR angiography, MR venography and MR perfusion sequences. Furthermore, some of the MRI contrast media employ other chemical elements than gadolinium, e.g. iron and manganese.

Gadolinium contrast agents are subcategorised into:

  • ionic or non-ionic: based on their net charge in solution

  • linear or macrocyclic: based on the molecular structure of the organic ligand (may be ionic or non-ionic)

Tissue that demonstrates enhancement following administration of gadolinium-containing IV contrast does so because of a combination of the following two mechanisms 3

  • intravascular enhancement

  • interstitial enhancement

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

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

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

Adverse reactions to gadolinium contrast agents are relatively rare, occurring in 0.04-0.3% of administrations, of which 0.4-9% are severe 1-6. These adverse reactions can be acute or chronic.

There is a 30% possibility of recurrence of hypersensitivity in patients who have had a previous hypersensitivity episode to gadolinium contrast agents 9. The risk of adverse reactions is higher in patients with bronchial asthma, a history of reactions to iodine-based contrast media, or others.

Gadolinium deposits in trace amounts in various organs, especially the brain (e.g. dentate nucleus of the cerebellum, globus pallidus) following administration of gadolinium contrast agents. The clinical significance of gadolinium deposition is thus far unknown 4.

Non-contrasted MR imaging such as arterial spin labeling (ASL), time of flight (TOF), phase contrast (PC), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS), susceptibility-weighted imaging (SWI), and amide proton transfer (APT) imaging may provide an alternative imaging technique in answering specific diagnostic questions 13.

See full article here: nephrogenic systemic fibrosis (NSF)

There is an association between the use of gadolinium-based contrast agents in patients with renal failure and nephrogenic systemic fibrosis (NSF). However, nearly all unconfounded cases of nephrogenic systemic fibrosis have been linked to one of the three linear Group I gadolinium contrast agents. 

Recent consensus states that the risk of nephrogenic systemic fibrosis or nephrotoxicity following administration of a Group II gadolinium contrast agent is extremely low, and that the potential harm of delayed diagnosis or misdiagnosis from delaying or withholding Group II gadolinium contrast agent for a clinically indicated MRI in a patient with acute kidney injury or eGFR less than 30 mL/min/1.73 m2 may outweigh the risk of nephrogenic systemic fibrosis, regardless of dialysis status 11

The ACR has divided gadolinium-based contrast agents into three groups depending on the risk of nephrogenic systemic fibrosis 10-12

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.

Gadolinium contrast agents can be divided according to whether the carrier ligand is linear or macrocyclic, and whether they are ionic or nonionic. This leads to four groupings:

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