Skip to main content
Top
Published in: European Radiology 11/2018

01-11-2018 | Neuro

Gadolinium deposition within the paediatric brain: no increased intrinsic T1-weighted signal intensity within the dentate nucleus following the administration of a minimum of four doses of the macrocyclic agent gadobutrol

Authors: Jonathan R. Young, Joe Qiao, Iren Orosz, Noriko Salamon, Mark A. Franke, Hyun J. Kim, Whitney B. Pope

Published in: European Radiology | Issue 11/2018

Login to get access

Abstract

Objectives

To determine whether repeated administration of the macrocyclic gadolinium-based contrast agent (GBCA) gadobutrol in children is associated with T1-weighted hyperintensity within the dentate nucleus, an imaging surrogate for gadolinium deposition.

Methods

With institutional review board approval, we identified a cohort of eight patients aged 18 years or younger who underwent at least four gadobutrol-enhanced magnetic resonance imaging (MRI) examinations of the brain from 2013 to 2017. For comparison, we identified a cohort of 19 patients who underwent at least four gadopentetate dimeglumine-enhanced MRI examinations. For each examination, both dentate nuclei were contoured on unenhanced images; the mean dentate-to-pons signal intensity (DN-P SI) ratio was calculated. DN-P SI ratios from the first and last MRI exams were compared using Wilcoxon signed ranks tests and linear regression analyses.

Results

In the gadobutrol cohort, there was no significant change in the mean DN-P SI ratio from the first to the last scan (1.02 vs 1.02, p = 1.00). In the gadopentetate dimeglumine cohort, there was a significant increase in the mean DN-P SI ratio from the first to the last scan (1.05 vs 1.13, p = 0.003). After controlling for potentially confounding variables, the change in DN-P SI ratio from the first to the last scan was significantly lower for patients in the gadobutrol group than in the gadopentetate dimeglumine group (β = -0.08, p = 0.04).

Conclusions

Repeated administration of the macrocyclic GBCA gadobutrol in children was not associated with T1-weighted dentate hyperintensity, while the repeated administration of the linear GBCA gadopentetate dimeglumine was associated with T1-weighted dentate hyperintensity, presumably due to gadolinium deposition.

Key Points

• Gadolinium-based contrast agents are routinely used in magnetic resonance imaging.
• Repeated administration of the macrocyclic agent gadobutrol in children was not associated with T1-weighted dentate hyperintensity.
Literature
1.
go back to reference Adin ME, Kleinberg L, Vaidya D, Zan E, Mirbagheri S, Yousem DM (2015) Hyperintense dentate nuclei on T1-weighted MRI: relation to repeat gadolinium administration. AJNR Am J Neuroradiol 36:1859–1865CrossRef Adin ME, Kleinberg L, Vaidya D, Zan E, Mirbagheri S, Yousem DM (2015) Hyperintense dentate nuclei on T1-weighted MRI: relation to repeat gadolinium administration. AJNR Am J Neuroradiol 36:1859–1865CrossRef
2.
go back to reference Errante Y, Cirimele V, Mallio CA, Di Lazzaro V, Zobel BB, Quattrocchi CC (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. Invest Radiol 49:685–690CrossRef Errante Y, Cirimele V, Mallio CA, Di Lazzaro V, Zobel BB, Quattrocchi CC (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. Invest Radiol 49:685–690CrossRef
3.
go back to reference Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D (2014) 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. Radiology 270:834–841CrossRef Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D (2014) 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. Radiology 270:834–841CrossRef
4.
go back to reference Kanda T, Osawa M, Oba H et al (2015) High signal intensity in dentate nucleus on unenhanced T1-weighted MR images: association with linear versus macrocyclic gadolinium chelate administration. Radiology 275:803–809CrossRef Kanda T, Osawa M, Oba H et al (2015) High signal intensity in dentate nucleus on unenhanced T1-weighted MR images: association with linear versus macrocyclic gadolinium chelate administration. Radiology 275:803–809CrossRef
5.
go back to reference McDonald RJ, McDonald JS, Kallmes DF et al (2015) Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology 275:772–782CrossRef McDonald RJ, McDonald JS, Kallmes DF et al (2015) Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology 275:772–782CrossRef
6.
go back to reference McDonald RJ, McDonald JS, Kallmes DF et al (2017) Gadolinium deposition in human brain tissues after contrast-enhanced MR imaging in adult patients without intracranial abnormalities. Radiology 285:546–554CrossRef McDonald RJ, McDonald JS, Kallmes DF et al (2017) Gadolinium deposition in human brain tissues after contrast-enhanced MR imaging in adult patients without intracranial abnormalities. Radiology 285:546–554CrossRef
7.
go back to reference Quattrocchi CC, Mallio CA, Errante Y et al (2015) 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. Invest Radiol 50:470–472CrossRef Quattrocchi CC, Mallio CA, Errante Y et al (2015) 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. Invest Radiol 50:470–472CrossRef
8.
go back to reference Radbruch A, Weberling LD, Kieslich PJ et al (2015) Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent. Radiology 275:783–791CrossRef Radbruch A, Weberling LD, Kieslich PJ et al (2015) Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent. Radiology 275:783–791CrossRef
9.
go back to reference Ramalho J, Castillo M, AlObaidy M et al (2015) High signal intensity in globus pallidus and dentate nucleus on unenhanced T1-weighted MR images: evaluation of two linear gadolinium-based contrast agents. Radiology 276:836–844CrossRef Ramalho J, Castillo M, AlObaidy M et al (2015) High signal intensity in globus pallidus and dentate nucleus on unenhanced T1-weighted MR images: evaluation of two linear gadolinium-based contrast agents. Radiology 276:836–844CrossRef
10.
go back to reference Blakemore SJ (2012) Imaging brain development: the adolescent brain. Neuroimage 61:397–406CrossRef Blakemore SJ (2012) Imaging brain development: the adolescent brain. Neuroimage 61:397–406CrossRef
11.
go back to reference Stein J, Schettler T, Wallinga D, Valenti M (2002) In harm's way: toxic threats to child development. J Dev Behav Pediatr 23:S13–S22CrossRef Stein J, Schettler T, Wallinga D, Valenti M (2002) In harm's way: toxic threats to child development. J Dev Behav Pediatr 23:S13–S22CrossRef
12.
go back to reference Flood TF, Stence NV, Maloney JA, Mirsky DM (2017) Pediatric brain: repeated exposure to linear gadolinium-based contrast material is associated with increased signal intensity at unenhanced T1-weighted MR imaging. Radiology 282:222–228CrossRef Flood TF, Stence NV, Maloney JA, Mirsky DM (2017) Pediatric brain: repeated exposure to linear gadolinium-based contrast material is associated with increased signal intensity at unenhanced T1-weighted MR imaging. Radiology 282:222–228CrossRef
13.
go back to reference Hu HH, Pokorney A, Towbin RB, Miller JH (2016) Increased signal intensities in the dentate nucleus and globus pallidus on unenhanced T1-weighted images: evidence in children undergoing multiple gadolinium MRI exams. Pediatr Radiol 46:1590–1598CrossRef Hu HH, Pokorney A, Towbin RB, Miller JH (2016) Increased signal intensities in the dentate nucleus and globus pallidus on unenhanced T1-weighted images: evidence in children undergoing multiple gadolinium MRI exams. Pediatr Radiol 46:1590–1598CrossRef
14.
go back to reference Roberts DR, Chatterjee AR, Yazdani M et al (2016) Pediatric patients demonstrate progressive T1-weighted hyperintensity in the dentate nucleus following multiple doses of gadolinium-based contrast agent. AJNR Am J Neuroradiol 37:2340–2347CrossRef Roberts DR, Chatterjee AR, Yazdani M et al (2016) Pediatric patients demonstrate progressive T1-weighted hyperintensity in the dentate nucleus following multiple doses of gadolinium-based contrast agent. AJNR Am J Neuroradiol 37:2340–2347CrossRef
15.
go back to reference Young JR, Orosz I, Franke MA et al (2017) Gadolinium deposition in the paediatric brain: T1-weighted hyperintensity within the dentate nucleus following repeated gadolinium-based contrast agent administration. Clin Radiol 73:290–295CrossRef Young JR, Orosz I, Franke MA et al (2017) Gadolinium deposition in the paediatric brain: T1-weighted hyperintensity within the dentate nucleus following repeated gadolinium-based contrast agent administration. Clin Radiol 73:290–295CrossRef
16.
go back to reference Radbruch A, Haase R, Kickingereder P et al (2017) 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. Radiology 283:828–836CrossRef Radbruch A, Haase R, Kickingereder P et al (2017) 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. Radiology 283:828–836CrossRef
17.
go back to reference Ryu YJ, Choi YH, Cheon JE et al (2018) Pediatric brain: gadolinium deposition in dentate nucleus and globus pallidus on unenhanced T1-weighted images is dependent on the type of contrast agent. Invest Radiol 53:246–255CrossRef Ryu YJ, Choi YH, Cheon JE et al (2018) Pediatric brain: gadolinium deposition in dentate nucleus and globus pallidus on unenhanced T1-weighted images is dependent on the type of contrast agent. Invest Radiol 53:246–255CrossRef
18.
go back to reference Tibussek D, Rademacher C, Caspers J et al (2017) Gadolinium brain deposition after macrocyclic gadolinium administration: a pediatric case-control study. Radiology 285:223–230CrossRef Tibussek D, Rademacher C, Caspers J et al (2017) Gadolinium brain deposition after macrocyclic gadolinium administration: a pediatric case-control study. Radiology 285:223–230CrossRef
19.
go back to reference Rossi Espagnet MC, Bernardi B, Pasquini L, Figa-Talamanca L, Toma P, Napolitano A (2017) 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. Pediatr Radiol 47:1345–1352CrossRef Rossi Espagnet MC, Bernardi B, Pasquini L, Figa-Talamanca L, Toma P, Napolitano A (2017) 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. Pediatr Radiol 47:1345–1352CrossRef
20.
go back to reference Radbruch A, Quattrocchi CC (2017) Interpreting signal-intensity ratios without visible T1 hyperintensities in clinical gadolinium retention studies. Pediatr Radiol 47:1688–1689CrossRef Radbruch A, Quattrocchi CC (2017) Interpreting signal-intensity ratios without visible T1 hyperintensities in clinical gadolinium retention studies. Pediatr Radiol 47:1688–1689CrossRef
21.
go back to reference Radbruch A, Haase R, Kieslich PJ et al (2017) 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. Radiology 282:699–707CrossRef Radbruch A, Haase R, Kieslich PJ et al (2017) 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. Radiology 282:699–707CrossRef
22.
go back to reference Stojanov DA, Aracki-Trenkic A, Vojinovic S, Benedeto-Stojanov D, Ljubisavljevic S (2016) 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 26:807–815CrossRef Stojanov DA, Aracki-Trenkic A, Vojinovic S, Benedeto-Stojanov D, Ljubisavljevic S (2016) 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 26:807–815CrossRef
23.
go back to reference Agris J, Pietsch H, Balzer T (2016) 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 Radiol 26:816–817CrossRef Agris J, Pietsch H, Balzer T (2016) 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 Radiol 26:816–817CrossRef
24.
go back to reference Renz DM, Kumpel S, Bottcher J et al (2018) Comparison of unenhanced T1-weighted signal intensities within the dentate nucleus and the globus pallidus after serial applications of gadopentetate dimeglumine versus gadobutrol in a pediatric population. Invest Radiol 53:119–127CrossRef Renz DM, Kumpel S, Bottcher J et al (2018) Comparison of unenhanced T1-weighted signal intensities within the dentate nucleus and the globus pallidus after serial applications of gadopentetate dimeglumine versus gadobutrol in a pediatric population. Invest Radiol 53:119–127CrossRef
25.
go back to reference Ramalho J, Ramalho M, AlObaidy M, Semelka RC (2016) Technical aspects of MRI signal change quantification after gadolinium-based contrast agents' administration. Magn Reson Imaging 34:1355–1358CrossRef Ramalho J, Ramalho M, AlObaidy M, Semelka RC (2016) Technical aspects of MRI signal change quantification after gadolinium-based contrast agents' administration. Magn Reson Imaging 34:1355–1358CrossRef
26.
go back to reference Hinoda T, Fushimi Y, Okada T et al (2017) Quantitative assessment of gadolinium deposition in dentate nucleus using quantitative susceptibility mapping. J Magn Reson Imaging 45:1352–1358CrossRef Hinoda T, Fushimi Y, Okada T et al (2017) Quantitative assessment of gadolinium deposition in dentate nucleus using quantitative susceptibility mapping. J Magn Reson Imaging 45:1352–1358CrossRef
27.
go back to reference Young JR, Orosz I, Franke MA et al (2018) Gadolinium deposition in the paediatric brain: T1-weighted hyperintensity within the dentate nucleus following repeated gadolinium-based contrast agent administration. Clin Radiol 73:290–295CrossRef Young JR, Orosz I, Franke MA et al (2018) Gadolinium deposition in the paediatric brain: T1-weighted hyperintensity within the dentate nucleus following repeated gadolinium-based contrast agent administration. Clin Radiol 73:290–295CrossRef
Metadata
Title
Gadolinium deposition within the paediatric brain: no increased intrinsic T1-weighted signal intensity within the dentate nucleus following the administration of a minimum of four doses of the macrocyclic agent gadobutrol
Authors
Jonathan R. Young
Joe Qiao
Iren Orosz
Noriko Salamon
Mark A. Franke
Hyun J. Kim
Whitney B. Pope
Publication date
01-11-2018
Publisher
Springer Berlin Heidelberg
Published in
European Radiology / Issue 11/2018
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-018-5464-5

Other articles of this Issue 11/2018

European Radiology 11/2018 Go to the issue