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European Radiology

, Volume 28, Issue 11, pp 4882–4889 | Cite as

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

  • Jonathan R. Young
  • Joe Qiao
  • Iren Orosz
  • Noriko Salamon
  • Mark A. Franke
  • Hyun J. Kim
  • Whitney B. Pope
Neuro
  • 229 Downloads

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.

Keywords

Gadolinium Contrast media Magnetic resonance imaging Cerebellar nuclei Paediatrics 

Abbreviations

DN-P SI

Dentate-to-pons signal intensity

GBCA

Gadolinium-based contrast agent

MP-RAGE

Magnetisation preparation rapid acquisition gradient-echo

Notes

Funding

The authors state that this work has not received any funding.

Compliance with ethical standards

Guarantor

The scientific guarantor of this publication is Whitney B. Pope, MD, PhD.

Conflict of interest

Whitney B. Pope, MD, PhD, is a consultant for Guerbet and Bracco.

Statistics and biometry

One of the authors, Hyun J. Kim, PhD, has significant statistical expertise.

Informed consent

Written informed consent was waived by the institutional review board.

Ethical approval

Institutional review board approval was obtained.

Methodology

• retrospective

• performed at one institution

References

  1. 1.
    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 36:1859–1865CrossRefGoogle Scholar
  2. 2.
    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 49:685–690CrossRefGoogle Scholar
  3. 3.
    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 270:834–841CrossRefGoogle Scholar
  4. 4.
    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 275:803–809CrossRefGoogle Scholar
  5. 5.
    McDonald RJ, McDonald JS, Kallmes DF et al (2015) Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology 275:772–782CrossRefGoogle Scholar
  6. 6.
    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 285:546–554CrossRefGoogle Scholar
  7. 7.
    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 50:470–472CrossRefGoogle Scholar
  8. 8.
    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 275:783–791CrossRefGoogle Scholar
  9. 9.
    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 276:836–844CrossRefGoogle Scholar
  10. 10.
    Blakemore SJ (2012) Imaging brain development: the adolescent brain. Neuroimage 61:397–406CrossRefGoogle Scholar
  11. 11.
    Stein J, Schettler T, Wallinga D, Valenti M (2002) In harm's way: toxic threats to child development. J Dev Behav Pediatr 23:S13–S22CrossRefGoogle Scholar
  12. 12.
    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 282:222–228CrossRefGoogle Scholar
  13. 13.
    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 46:1590–1598CrossRefGoogle Scholar
  14. 14.
    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 37:2340–2347CrossRefGoogle Scholar
  15. 15.
    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 73:290–295CrossRefGoogle Scholar
  16. 16.
    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 283:828–836CrossRefGoogle Scholar
  17. 17.
    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 53:246–255CrossRefGoogle Scholar
  18. 18.
    Tibussek D, Rademacher C, Caspers J et al (2017) Gadolinium brain deposition after macrocyclic gadolinium administration: a pediatric case-control study. Radiology 285:223–230CrossRefGoogle Scholar
  19. 19.
    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 47:1345–1352CrossRefGoogle Scholar
  20. 20.
    Radbruch A, Quattrocchi CC (2017) Interpreting signal-intensity ratios without visible T1 hyperintensities in clinical gadolinium retention studies. Pediatr Radiol 47:1688–1689CrossRefGoogle Scholar
  21. 21.
    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 282:699–707CrossRefGoogle Scholar
  22. 22.
    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 26:807–815CrossRefGoogle Scholar
  23. 23.
    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 26:816–817CrossRefGoogle Scholar
  24. 24.
    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 53:119–127CrossRefGoogle Scholar
  25. 25.
    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 34:1355–1358CrossRefGoogle Scholar
  26. 26.
    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 45:1352–1358CrossRefGoogle Scholar
  27. 27.
    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 73:290–295CrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2018

Authors and Affiliations

  • Jonathan R. Young
    • 1
  • Joe Qiao
    • 2
  • Iren Orosz
    • 2
  • Noriko Salamon
    • 2
  • Mark A. Franke
    • 2
  • Hyun J. Kim
    • 2
  • Whitney B. Pope
    • 2
  1. 1.Department of RadiologyUC Davis School of MedicineSacramentoUSA
  2. 2.Department of RadiologyDavid Geffen School of Medicine at UCLALos AngelesUSA

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