REVIEW ARTICLE
https://doi.org/10.1007/s00062-018-0678-0
Clin Neuroradiol (2018) 28:159–169
A Review of the Current Evidence on Gadolinium Deposition in the
Brain
Richard Pullicino
1
· Mark Radon
1
· Shubhabrata Biswas
1
· Maneesh Bhojak
1
·KumarDas
1
Received: 18 November 2017 / Accepted: 20 February 2018 / Published online: 9 March 2018
© Springer-Verlag GmbH Germany, part of Springer Nature 2018
Abstract
Over the past 3 years, gadolinium-based contrast agents have been linked to MRI signal changes in the brain, which have
been found to be secondary to gadolinium deposition in the brain, particularly in the dentate nuclei and globus pallidus
even in patients having an intact blood-brain barrier and a normal renal function. This tends to occur more in linear agents
than with macrocyclic agents. Nonetheless, there has been no significant evidence that this has any clinical consequence.
We reviewed the current evidence related to this new phenomenon and the precautionary approach taken by regulatory
agencies.
Keywords Gadolinium-based contrast agents · Gadolinium deposition · Pharmacokinetics · Dentate nucleus · Regulation
Abbreviations
BBB Blood-brain barrier
CMSC Consortium of Multiple Sclerosis Centers
CSF Cerebrospinal fluid
DN Dentate nucleus
EMA European Medicines Agency
FDA U.S. Food and Drug Administration
Fe Iron
GBCA Gadolinium-based contrast agent
Gd Gadolinium
GP Globus pallidus
ICP-MS Inductively coupled plasma mass spectrome-
try
LA-ICP-MS Laser ablation inductively coupled plasma
mass spectrometry
MRI Magnetic resonance imaging
MS Multiple sclerosis
NSF Nephrogenic systemic fibrosis
QSM Quantitative-susceptibility mapping
SEM/EDS Scanning electron microscopy/energy disper-
sive X-ray spectroscopy
Richard Pullicino
richard.pullicino@gmail.com
1
Neuroradiology Department, The Walton Centre NHS
Foundation Trust, Lower Lane, Liverpool, L9 7LJ, UK
Introduction
The use of gadolinium-based contrast agents (GBCA) in hu-
mans [1, 2], dramatically expanded the diagnostic capabil-
ities of magnetic resonance imaging (MRI) and 30 million
doses of GBCA are administered annually in both clinical
and research settings [3]. Initially, it was thought that the
only risks associated with these agents would be allergic
reactions and similar acute adverse events. The first case
of nephrogenic systemic fibrosis (NSF) [4] was reported
in 1997 and 9 years later this condition was eventually
linked to gadolinium (Gd) exposure [5–7]. The incidence
of NSF has been lowered dramatically by decreasing the
dosage and limiting administration of these agents in high-
risk patients. Over the past 3 years, evidence for deposi-
tion of these agents in the brain during clinical use has
come to light: first on imaging as high-T1 signal intensity
in the dentate nuclei (DN) (Fig. 1) and globus pallidus (GP)
and subsequently the detection of Gd in both autopsy and
biopsy tissue studies [8–10]. The question as to whether
there is a clinical syndrome associated with Gd deposition
remains open, although no definitive evidence has so far
been published [11–15].
Chemistry and Properties of Gadolinium
Contrast Agents
Contrast agents in MRI increase the contrast between the
cavity, vessel or organ in which they are present and the
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