A Review of the Current Evidence on Gadolinium Deposition in the Brain

A Review of the Current Evidence on Gadolinium Deposition in the Brain 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Klinische Neuroradiologie Springer Journals

A Review of the Current Evidence on Gadolinium Deposition in the Brain

Download PDF
11 pages
Read Article

Loading next page...
 
/lp/springer_journal/a-review-of-the-current-evidence-on-gadolinium-deposition-in-the-brain-sgGMTD8Rx1
Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer-Verlag GmbH Germany, part of Springer Nature
Subject
Medicine & Public Health; Neuroradiology; Neurosurgery; Neurology
ISSN
0939-7116
eISSN
1869-1447
DOI
10.1007/s00062-018-0678-0
Publisher site
See Article on Publisher Site

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.

Journal

Klinische Neuroradiologie – Springer Journals

Published: Mar 9, 2018

References

  • First use of GdDTPA/dimeglumine in man
    Laniado, M; Weinmann, HJ; Schörner, W; Felix, R; Speck, U
  • Dyke Award. Evaluation of contrast-enhanced MR imaging in a brain-abscess model
    Runge, VM; Clanton, JA; Price, AC; Herzer, WA; Allen, JH; Partain, CL
  • Safety of the gadolinium-based contrast agents for magnetic resonance imaging, focusing in part on their accumulation in the brain and especially the dentate nucleus
    Runge, VM
  • Scleromyxoedema-like cutaneous diseases in renal-dialysis patients
    Cowper, SE; Robin, HS; Steinberg, SM; Su, LD; Gupta, S; LeBoit, PE
  • Gadolinium—a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis?
    Grobner, T
  • An epidemic outbreak of nephrogenic systemic fibrosis in a Danish hospital
    Marckmann, P
  • Gadolinium-induced nephrogenic systemic fibrosis: the rise and fall of an iatrogenic disease
    Bennett, CL; Qureshi, ZP; Sartor, AO; Norris, LB; Murday, A; Xirasagar, S
  • Intracranial gadolinium deposition after contrast-enhanced MR imaging
    McDonald, RJ; McDonald, JS; Kallmes, DF; Jentoft, ME; Murray, DL; Thielen, KR
  • Gadolinium released from MR contrast agents is deposited in brain tumors: in situdemonstration using scanning electron microscopy with energy dispersive X‑ray spectroscopy
    Xia, D; Davis, RL; Crawford, JA; Abraham, JL
  • 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
    Kanda, T; Fukusato, T; Matsuda, M; Toyoda, K; Oba, H; Kotoku, J
  • Gadolinium based contrast agents (GBCA): safety overview after 3 decades of clinical experience
    Kanal, E
  • How the chemical properties of gadolinium-based contrast agents and the use of animal models inform us about the behavior of these agents in the human brain
    Gadolinium Retention, LRE; Revisited, D
  • Gadolinium retention in the body: what we know and what we can do
    Tedeschi, E; Caranci, F; Giordano, F; Angelini, V; Cocozza, S; Brunetti, A
  • Distribution and chemical forms of gadolinium in the brain: a review
    Kanda, T; Nakai, Y; Hagiwara, A; Oba, H; Toyoda, K; Furui, S
  • The presence of the gadolinium-based contrast agent depositions in the brain and symptoms of gadolinium neurotoxicity—a systematic review
    Olchowy, C; Cebulski, K; Łasecki, M; Chaber, R; Olchowy, A; Kałwak, K
  • Biodistribution of gadolinium-based contrast agents, including gadolinium deposition
    Aime, S; Caravan, P
  • Reaction of gadolinium chelates with endogenously available ions
    Tweedle, MF; Hagan, JJ; Kumar, K; Mantha, S; Chang, CA
  • Primer on gadolinium chemistry
    Sherry, AD; Caravan, P; Lenkinski, RE
  • What nephrologists need to know about gadolinium
    Penfield, JG; Reilly, RF
  • Stability of gadolinium-based magnetic resonance imaging contrast agents in human serum at 37°C
    Frenzel, T; Lengsfeld, P; Schirmer, H; Hütter, J; Weinmann, H-J
  • Kinetics of formation and dissociation of lanthanide (III)-DOTA complexes
    Toth, E; Brücher, E; Lazar, I; Toth, I
  • Studies on the kinetic stabilities of the Gd(3+) complexes formed with the N‑mono(methylamide), N′-mono(methylamide) and N,N″-bis(methylamide) derivatives of diethylenetriamine-N,N,N′,N′,N′-pentaacetic acid
    Sarka, L; Burai, L; Király, R; Zékány, L; Brücher, E
  • Gadolinium(III) chelates as MRI contrast agents:  structure, dynamics, and applications
    Caravan, P; Ellison, JJ; McMurry, TJ; Lauffer, RB
  • Human in vivo comparative study of zinc and copper transmetallation after administration of magnetic resonance imaging contrast agents
    Puttagunta, NR; Gibby, WA; Smith, GT
  • Comparison of Gd DTPA-BMA (Omniscan) versus Gd HP-DO3A (ProHance) retention in human bone tissue by inductively coupled plasma atomic emission spectroscopy
    Gibby, WA; Gibby, KA; Gibby, WA
  • Comparative study of the physicochemical properties of six clinical low molecular weight gadolinium contrast agents
    Laurent, S; Elst, LV; Muller, RN
  • Hyperintense dentate nucleus on unenhanced T1-weighted MR images is associated with the secondary progressive subtype
    Roccatagliata, L; Vuolo, L; Bonzano, L; Pichiecchio, A; Multiple Sclerosis, MGL
  • Dentate nucleus T1 hyperintensity in multiple sclerosis
    Absinta, M; Rocca, MA; Filippi, M
  • Hyperintense dentate nucleus on unenhanced T1-weighted MR images is associated with a history of brain irradiation
    Kasahara, S; Miki, Y; Kanagaki, M; Yamamoto, A; Mori, N; Sawada, T
  • High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material
    Kanda, T; Ishii, K; Kawaguchi, H; Kitajima, K; Takenaka, D
  • Epidemiology of multiple sclerosis
    Leray, E; Moreau, T; Fromont, A; Edan, G
  • Extent of signal hyperintensity on unenhanced T1-weighted brain MR images after more than 35 administrations of linear gadolinium-based contrast agents
    Zhang, Y; Cao, Y; Shih, GL; Hecht, EM; Prince, MR
  • T1 shortening in the cerebral cortex after multiple administrations of gadolinium-based contrast agents
    Khant, ZA; Hirai, T; Kadota, Y; Masuda, R; Yano, T; Azuma, M
  • In vivo dentate nucleus MRI relaxometry correlates with previous administration of gadolinium-based contrast agents
    Tedeschi, E; Palma, G; Canna, A; Cocozza, S; Russo, C; Borrelli, P
  • Quantitative assessment of gadolinium deposition in dentate nucleus using quantitative susceptibility mapping
    Hinoda, T; Fushimi, Y; Okada, T; Arakawa, Y; Liu, C; Yamamoto, A
  • Longitudinal assessment of dentate nuclei relaxometry during massive gadobutrol exposure
    Tedeschi, E; Cocozza, S; Borrelli, P; Ugga, L; Morra, VB; Palma, G
  • No signal intensity increase in the dentate nucleus on unenhanced T1-weighted MR images after more than 20 serial injections of macrocyclic gadolinium-based contrast agents
    Radbruch, A; Haase, R; Kieslich, PJ; Weberling, LD; Kickingereder, P; Wick, W
  • Pediatric brain: repeated exposure to linear gadolinium-based contrast material is associated with increased signal intensity at unenhanced T1-weighted MR imaging
    Flood, TF; Stence, NV; Maloney, JA; Mirsky, DM
  • Increased signal intensities in the dentate nucleus and globus pallidus on unenhanced T1-weighted images: evidence in children undergoing multiple gadolinium MRI exams. Pediatric Radiology
    Hu, HH; Pokorney, A; Towbin, RB; Miller, JH
  • Pediatric patients demonstrate progressive T1-weighted hyperintensity in the dentate nucleus following multiple doses of gadolinium-based contrast agent
    Roberts, DR; Chatterjee, AR; Yazdani, M; Marebwa, B; Brown, T; Collins, H
  • Gadolinium brain deposition after macrocyclic gadolinium administration: a pediatric case-control study
    Tibussek, D; Rademacher, C; Caspers, J; Turowski, B; Schaper, J; Antoch, G
  • Pediatric brain: no increased signal intensity in the dentate nucleus on unenhanced T1-weighted MR images after consecutive exposure to a macrocyclic gadolinium-based contrast agent
    Radbruch, A; Haase, R; Kickingereder, P; Bäumer, P; Bickelhaupt, S; Paech, D
  • 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
    Stojanov, DA; Aracki-Trenkic, A; Vojinovic, S; Benedeto-Stojanov, D; Ljubisavljevic, S
  • 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?
    Agris, J; Pietsch, H; Balzer, T
  • Intraindividual analysis of signal intensity changes in the dentate nucleus after consecutive serial applications of linear and macrocyclic gadolinium-based contrast agents
    Radbruch, A; Weberling, LD; Kieslich, PJ; Hepp, J; Kickingereder, P; Wick, W
  • Signal change in the dentate nucleus on T1-weighted MR images after multiple administrations of gadopentetate fimeglumine versus gadobutrol
    Cao, Y; Huang, DQ; Shih, G; Prince, MR
  • High signal intensity in dentate nucleus on unenhanced T1-weighted MR images: association with linear versus macrocyclic gadolinium chelate administration
    Kanda, T; Osawa, M; Oba, H; Toyoda, K; Kotoku, J; Haruyama, T
  • T1 signal measurements in pediatric brain: findings after multiple exposures to gadobenate dimeglumine for imaging of nonneurologic disease
    Schneider, GK; Stroeder, J; Roditi, G; Colosimo, C; Armstrong, P; Martucci, M
  • Signal intensity at unenhanced T1-weighted magnetic resonance in the globus pallidus and dentate nucleus after serial administrations of a macrocyclic gadolinium-based contrast agent in children
    Rossi Espagnet, MC; Bernardi, B; Pasquini, L; Figà-Talamanca, L; Tomà, P; Napolitano, A
  • Interpreting signal-intensity ratios without visible T1 hyperintensities in clinical gadolinium retention studies
    Radbruch, A; Quattrocchi, CC
  • Quantification and assessment of the chemical form of residual gadolinium in the brain after repeated administration of gadolinium-based contrast agents: comparative study in rats
    Frenzel, T; Apte, C; Jost, G; Schöckel, L; Lohrke, J; Pietsch, H
  • Distribution map of gadolinium deposition within the cerebellum following GBCA administration
    Roberts, DR; Welsh, CA; LeBel, DP; Davis, WC
  • Reply to Radbruch et al.: ‘interpreting signal-intensity ratios without visible T1 hyperintensities in clinical gadolinium retention studies’
    Rossi Espagnet, MC; Tomà, P; Napolitano, A
  • The microvasculature of the human cerebellar meninges
    Nonaka, H; Akima, M; Hatori, T; Nagayama, T; Zhang, Z; Ihara, F
  • Gadolinium deposition in human brain tissues after contrast-enhanced MR imaging in adult patients without Intracranial abnormalities
    McDonald, RJ; McDonald, JS; Kallmes, DF; Jentoft, ME; Paolini, MA; Murray, DL
  • Macrocyclic and other non-group 1 gadolinium contrast agents deposit low levels of gadolinium in brain and bone tissue: preliminary results from 9 patients with normal renal function
    Murata, N; Gonzalez-Cuyar, LF; Murata, K; Fligner, C; Dills, R; Hippe, D
  • T1-weighted hypersignal in the deep cerebellar nuclei after repeated administrations of gadolinium-based contrast agents in healthy rats: difference between linear and macrocyclic agents
    Robert, P; Lehericy, S; Grand, S; Violas, X; Fretellier, N; Idée, J-M
  • Signal increase on unenhanced T1-weighted images in the rat brain after repeated, extended doses of gadolinium-based contrast agents: comparison of linear and macrocyclic agents
    Jost, G; Lenhard, DC; Sieber, MA; Lohrke, J; Frenzel, T; Pietsch, H
  • Linear gadolinium-based contrast agents are associated with brain gadolinium retention in healthy rats
    Robert, P; Violas, X; Grand, S; Lehericy, S; Idée, J-M; Ballet, S
  • Clearance of gadolinium from the brain with no pathologic effect after repeated administration of gadodiamide in healthy rats: an analytical and histologic study
    Smith, APL; Marino, M; Roberts, J; Crowder, JM; Castle, J; Lowery, L
  • Gadolinium deposition in the brain: lessons learned from other metals known to cross the blood-brain barrier
    Prybylski, JP; Maxwell, E; Coste Sanchez, C; Jay, M
  • High signal intensity in globus pallidus and dentate nucleus on unenhanced T1-weighted MR images: evaluation of two linear gadolinium-based contrast agents
    Ramalho, J; Castillo, M; AlObaidy, M; Nunes, RH; Ramalho, M; Dale, BM
  • Increased signal intensity in the dentate nucleus on unenhanced T1-weighted images after gadobenate dimeglumine administration
    Weberling, LD; Kieslich, PJ; Kickingereder, P; Wick, W; Bendszus, M; Schlemmer, H-P
  • 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
    Roberts, DR; Holden, KR
  • Are some agents less likely to deposit gadolinium in the brain?
    Radbruch, A
  • Gadopentetate but not gadobutrol accumulates in the dentate nucleus of multiple sclerosis patients
    Schlemm, L; Chien, C; Bellmann-Strobl, J; Dörr, J; Wuerfel, J; Brandt, AU
  • Is there long-term signal intensity increase in the central nervous system on T1-weighted images after MR imaging with the hepatospecific contrast agent Gadoxetic acid? A cross-sectional study in 91 patients
    Kahn, J; Posch, H; Steffen, IG; Geisel, D; Bauknecht, C; Liebig, T
  • Brain uptake of trace metals, zinc and manganese
    Takeda, A; Akiyama, T; Sawashita, J; Okada, S
  • In vivo detection of neuroarchitecture in the rodent brain using manganese-enhanced MRI
    Aoki, I; Wu Y‑JL, SAC; Lynch, RM; Koretsky, AP
  • Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue
    Jost, G; Frenzel, T; Lohrke, J; Lenhard, DC; Naganawa, S; Pietsch, H
  • Changes in background blood-brain barrier integrity between lacunar and cortical ischemic stroke subtypes
    Wardlaw, JM; Farrall, A; Armitage, PA; Carpenter, T; Chappell, F; Doubal, F
  • Improved HYDROPS: imaging of endolymphatic hydrops after intravenous administration of gadolinium
    Naganawa, S; Kawai, H; Taoka, T; Sone, M
  • A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β
    Iliff, JJ; Wang, M; Liao, Y; Plogg, BA; Peng, W; Gundersen, GA
  • Brain-wide pathway for waste clearance captured by contrast-enhanced MRI
    Iliff, JJ; Lee, H; Yu, M; Feng, T; Logan, J; Nedergaard, M
  • Gadolinium retention, brain T1 hyperintensity, and endogenous metals: a comparative study of macrocyclic versus linear gadolinium chelates in renally sensitized rats
    Rasschaert, M; Emerit, A; Fretellier, N; Factor, C; Robert, P; Idée, J-M
  • Analytical interference in serum iron determination reveals iron versus gadolinium transmetallation with linear gadolinium-based contrast agents
    Fretellier, N; Poteau, N; Factor, C; Mayer, J-F; Medina, C; Port, M
  • Low-molecular-weight iron chelates may be an alternative to gadolinium-based contrast agents for T1-weighted contrast-enhanced MR imaging
    Boehm-Sturm, P; Haeckel, A; Hauptmann, R; Mueller, S; Kuhl, CK; Schellenberger, EA
  • Can gadolinium be re-chelated in vivo? Considerations from decorporation therapy
    Prybylski, JP; Semelka, RC; Jay, M
  • Nephrogenic systemic fibrosis manifesting a decade after exposure to gadolinium
    Larson, KN; Gagnon, AL; Darling, MD; Patterson, JW; Cropley, TG
  • Diagnosing nephrogenic systemic fibrosis in the post-FDA restriction era
    Thomson, LK; Thomson, PC; Kingsmore, DB; Blessing, K; Daly, CD; Cowper, SE
  • Functional imaging of the deep cerebellar nuclei: a review
    Habas, C
  • Unilateral lesions of the globus pallidus: report of four patients presenting with focal or segmental dystonia
    Münchau, A; Mathen, D; Cox, T; Quinn, NP; Marsden, CD; Bhatia, KP
  • Association between gadolinium contrast exposure and the risk of parkinsonism
    Welk, B; McArthur, E; Morrow, SA; MacDonald, P; Hayward, J; Leung, A
  • Retention of gadolinium-based contrast agents in multiple sclerosis: retrospective analysis of an 18-year longitudinal study
    Forslin, Y; Shams, S; Hashim, F; Aspelin, P; Bergendal, G; Martola, J
  • Brain gadolinium deposition varies with contrast agent in MS
  • Cumulative dose of macrocyclic gadolinium-based contrast agent improves detection of enhancing lesions in patients with multiple sclerosis
    Rovira, A; Auger, C; Huerga, E; Corral, JF; Mitjana, R; Sastre-Garriga, J
  • Gadolinium accumulation after contrast-enhanced magnetic resonance imaging: which implications in patients with Crohn’s disease?
    Savarino, E; Chianca, V; Bodini, G; Albano, D; Messina, C; Tontini, GE
  • A family of disorders
    Semelka, RC; Ramalho, M; AlObaidy, M; Gadolinium Humans, RJ
  • Gadolinium-based contrast agent accumulation and toxicity: an update
    Ramalho, J; Semelka, RC; Ramalho, M; Nunes, RH; AlObaidy, M; Castillo, M
  • Mono-, bi-, and trinuclear bis-hydrated Mn(2+) complexes as potential MRI contrast agents
    Forgács, A; Regueiro-Figueroa, M; Barriada, JL; Esteban-Gómez, D; Blas, A; Rodríguez-Blas, T
  • Nitroxide-based macromolecular contrast agents with unprecedented transverse relaxivity and stability for magnetic resonance imaging of tumors
    Nguyen, HVT; Chen, Q; Paletta, JT; Harvey, P; Jiang, Y; Zhang, H
  • FDA evaluating the risk of brain deposits with repeated use of gadolinium-based contrast agents for magnetic resonance imaging (MRI)
  • FDA warns that gadolinium-based contrast agents (GBCAs) are retained in the body; requires new class warnings
  • Gadolinium deposition in the brain: summary of evidence and recommendations
    Gulani, V; Calamante, F; Shellock, FG; Kanal, E; Reeder, SB
  • Chelated or dechelated gadolinium deposition
    Radbruch, A; Roberts, DR; Clement, O; Rovira, A; Quattrocchi, CC
  • EMA’s final opinion confirms restrictions on use of linear gadolinium agents in body scans
  • 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
    Errante, Y; Cirimele, V; Mallio, CA; Lazzaro, V; Zobel, BB; Quattrocchi, CC
  • High-signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted images
    Radbruch, A; Weberling, LD; Kieslich, PJ; Hepp, J; Kickingereder, P; Wick, W
  • Gadodiamide and dentate nucleus T1 hyperintensity in patients with meningioma evaluated by multiple follow-up contrast-enhanced magnetic resonance examinations with no systemic interval therapy
    Quattrocchi, CC; Mallio, CA; Errante, Y; Cirimele, V; Carideo, L; Ax, A

You’re reading a free preview. Subscribe to read the entire article.

Try 2 weeks free now

DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

or browse the journals available

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off

Sign up
for free
Start 14 day
Free Trial