Gadolinium deposition within the dentate nucleus and globus pallidus after repeated administrations of gadolinium-based contrast agents—current status
- 2.1k Downloads
Gadolinium-based contrast agents (GBCAs) have been used clinically since 1988 for contrast-enhanced magnetic resonance imaging (CE-MRI). Generally, GBCAs are considered to have an excellent safety profile. However, GBCA administration has been associated with increased occurrence of nephrogenic systemic fibrosis (NSF) in patients with severely compromised renal function, and several studies have shown evidence of gadolinium deposition in specific brain structures, the globus pallidus and dentate nucleus, in patients with normal renal function.
Gadolinium deposition in the brain following repeated CE-MRI scans has been demonstrated in patients using T1-weighted unenhanced MRI and inductively coupled plasma mass spectroscopy. Additionally, rodent studies with controlled GBCA administration also resulted in neural gadolinium deposits.
Repeated GBCA use is associated with gadolinium deposition in the brain. This is especially true with the use of less-stable, linear GBCAs. In spite of increasing evidence of gadolinium deposits in the brains of patients after multiple GBCA administrations, the clinical significance of these deposits continues to be unclear.
Here, we discuss the current state of scientific evidence surrounding gadolinium deposition in the brain following GBCA use, and the potential clinical significance of gadolinium deposition. There is considerable need for further research, both to understand the mechanism by which gadolinium deposition in the brain occurs and how it affects the patients in which it occurs.
KeywordsMagnetic resonance imaging Gadolinium deposition Contrast media Globus pallidus Dentate nucleus
Compliance with ethical standards
We declare that this manuscript does not contain clinical studies or patient data.
Conflict of interest
We declare that we have no conflict of interest.
- 7.Errante Y, Cirimele V, Mallio CA et al (2014) Progressive increase of T1 signal intensity of the dentate nucleus on unenhanced magnetic resonance images is associated with cumulative doses of intravenously administered gadodiamide in patients with normal renal function, suggesting dechelation. Investig Radiol 49:685–690CrossRefGoogle Scholar
- 12.Stojanov DA, Aracki-Trenkic A, Vojinovic S, Benedeto-Stojanov D, Jubisavljevic S (2015) Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol. Eur Radiol.Google Scholar
- 13.Kanda T, Fukusato T, Matsuda M, Toyoda K, Oba H, Kotoku J, Haruvama T, Kitajima K, Furui S (2015) Gadolinium-based contrast agent accumulates in the brain even in subjects without severe renal dysfunction: evaluation of autopsy brain specimens with inductively coupled plasma mass spectroscopy. Radiology 276(1):228–32CrossRefPubMedGoogle Scholar
- 16.Roberts D and Holden K (2015) Progressive increase of T1 signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images in the pediatric brain exposed to multiple doses of gadolinium contrast. Brain Dev.Google Scholar
- 20.Robert P, Violas X, Grand S, et al. (2015) Linear gadolinium-based contrast agents are associated with brain gadolinium retention in healthy rats. Invest Radiol.Google Scholar
- 22.United States Food and Drug Administration (2015) http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm456012.htm
- 29.Pirovano G, Munley J, Schultz C et al (2012) Nephrogenic systemic fibrosis: a review of published cases and results from three prospective observational studies. Insights Imaging 3(suppl 1):S293Google Scholar
- 33.American College of Radiology. Manual on Contrast Media. Version 10.1. 2015. http://www.acr.org
- 47.Beomonte Zobel B, Quattrocchi CC, Errante Y, Grasso RF (2015) Gadolinium-based contrast agents: did we miss something in the last 25 years? Radiol MedGoogle Scholar
- 48.Ramalho J, Semelka RC, Ramalho M, et al. (2015) Gadolinium-based contrast agent accumulation and toxicity: an update. AJNR Am J NeuroradiolGoogle Scholar
- 49.Thomsen HS (2016) T1 hyperintensity in the brain after multiple intravenous injections of gadolinium-based contrast agents. Acta RadiolGoogle Scholar
- 51.Agris J, Pietsch H, and Balzer T (2015) What evidence is there that gadobutrol causes increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W MRI in patients with RRMS? Eur RadiolGoogle Scholar
- 52.Stojanov D (2015) Reply to Letter to the Editor re: Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol. Eur RadiolGoogle Scholar
- 60.Tabanor K, Lee P, Kiptoo P, et al. (2016) Brain delivery of drug and MRI contrast agent: detection and quantitative determination of brain deposition of CPT-Glu using LC-MS/MS and Gd-DTPA using magnetic resonance imaging. Mol PharmGoogle Scholar
- 65.Chan DE, Pan HC, Ho DM et al (2007) Presence of activated microglia in a high-signal lesion on T1-weighted MR images: a biopsy sample re-examined. AJNR Am J Neuroradiol 28:602Google Scholar
- 79.Weinmann HJ, Gries H, Speck U (1992) Fundamental physics and chemistry: types of contrast agents. In: Sartor K (ed) MR imaging of the skull and brain: a correlative text atlas. Springer-Verlag, New York, pp 26–28Google Scholar
- 81.Kim TJ, Kim TO, Kim WS et al (2006) MR imaging of the brain in Wilson disease of childhood: findings before and after treatment with clinical correlation. AJNR Am J Neuroradiol 2(6):1373–1378Google Scholar
- 82.Lai PH, Chen C, Liang HL, Pan HB (1999) Hyperintense basal ganglia on T1-weighted MR imaging. AJNR Am J Neuroradiol 172(4):1109–1115Google Scholar
- 87.Mirowitz SA, Westicks TJ, Hirsch JD (1991) Hyperintense basal ganglia on T1-weighted MR images in patients receiving parenteral nutrition. Radiology 181(1):117–120Google Scholar