Gadolinium contrast agents
Citation, DOI, disclosures and article data
At the time the article was created Usman Bashir had no recorded disclosures.View Usman Bashir's current disclosures
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.
detection of focal lesions (e.g. tumor, abscess, metastasis)
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)
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 3:
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. 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.
Nephrogenic systemic fibrosis
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.
group I: greatest number of reported nephrogenic systemic fibrosis cases
group II: few, if any, cases of nephrogenic systemic fibrosis
group III: few, if any cases of nephrogenic systemic fibrosis but limited data available
gadoxetate disodium (Eovist, Primovist)
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:
Gd-DOTA, gadoterate meglumine (Dotarem, Artirem)
- 1. Gandhi SN, Brown MA, Wong JG et-al. MR contrast agents for liver imaging: what, when, how. Radiographics. 26 (6): 1621-36. doi:10.1148/rg.266065014 - Pubmed citation
- 2. Pretorius ES, MBA JASMD. Radiology Secrets Plus. Mosby. ISBN:0323067948. Read it at Google Books - Find it at Amazon
- 3. Smirniotopoulos JG, Murphy FM, Rushing EJ, Rees JH, Schroeder JW. Patterns of contrast enhancement in the brain and meninges. (2007) Radiographics : a review publication of the Radiological Society of North America, Inc. 27 (2): 525-51. doi:10.1148/rg.272065155 - Pubmed
- 4. Gulani V, Calamante F, Shellock FG, Kanal E, Reeder SB. Gadolinium deposition in the brain: summary of evidence and recommendations. (2017) The Lancet. Neurology. 16 (7): 564-570. doi:10.1016/S1474-4422(17)30158-8 - Pubmed
- 5. Jung JW, Kang HR, Kim MH, Lee W, Min KU, Han MH, Cho SH. Immediate hypersensitivity reaction to gadolinium-based MR contrast media. (2012) Radiology. 264 (2): 414-22. doi:10.1148/radiol.12112025 - Pubmed
- 6. Hunt CH, Hartman RP, Hesley GK. Frequency and severity of adverse effects of iodinated and gadolinium contrast materials: retrospective review of 456,930 doses. (2009) AJR. American journal of roentgenology. 193 (4): 1124-7. doi:10.2214/AJR.09.2520 - Pubmed
- 7. Dillman JR, Ellis JH, Cohan RH, Strouse PJ, Jan SC. Frequency and severity of acute allergic-like reactions to gadolinium-containing i.v. contrast media in children and adults. (2007) AJR. American journal of roentgenology. 189 (6): 1533-8. doi:10.2214/AJR.07.2554 - Pubmed
- 8. Prince MR, Zhang H, Zou Z, Staron RB, Brill PW. Incidence of immediate gadolinium contrast media reactions. (2011) AJR. American journal of roentgenology. 196 (2): W138-43. doi:10.2214/AJR.10.4885 - Pubmed
- 9. Jae-Woo Jung, Hye-Ryun Kang, Min-Hye Kim, Whal Lee, Kyung-Up Min, Moon-Hee Han, Sang-Heon Cho. Immediate Hypersensitivity Reaction to Gadolinium-based MR Contrast Media. (2012) Radiology. 264 (2): 414-22. doi:10.1148/radiol.12112025 - Pubmed
- 10. ACR Manual On Contrast Media - 2020. ACR Committee on Drugs and Contrast Media. page 85 PDF
- 11. Jeffrey C. Weinreb, Roger A. Rodby, Jerry Yee, Carolyn L. Wang, Derek Fine, Robert J. McDonald, Mark A. Perazella, Jonathan R. Dillman, Matthew S. Davenport. Use of Intravenous Gadolinium-based Contrast Media in Patients with Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation. (2020) Radiology. doi:10.1148/radiol.2020202903
- 12. Prasad R. Shankar, Matthew S. Davenport. Risk of Nephrogenic Systemic Fibrosis in Stage 4 and 5 Chronic Kidney Disease Following Group II Gadolinium-based Contrast Agent Administration: Subanalysis by Chronic Kidney Disease Stage. (2020) Radiology. doi:10.1148/radiol.2020201492
- 13. Falk Delgado A, Van Westen D, Nilsson M et al. Diagnostic Value Of alternative Techniques to Gadolinium-Based Contrast Agents in MR Neuroimaging—a Comprehensive Overview. Insights Imaging. 2019;10(1):84. doi:10.1186/s13244-019-0771-1 - Pubmed
- 14. Robic C, Port M, Rousseaux O et al. Physicochemical and Pharmacokinetic Profiles of Gadopiclenol: A New Macrocyclic Gadolinium Chelate With High T1 Relaxivity. Invest Radiol. 2019;54(8):475-84. doi:10.1097/RLI.0000000000000563 - Pubmed