Elsevier

Clinical Radiology

Volume 73, Issue 3, March 2018, Pages 290-295
Clinical Radiology

Gadolinium deposition in the paediatric brain: T1-weighted hyperintensity within the dentate nucleus following repeated gadolinium-based contrast agent administration

https://doi.org/10.1016/j.crad.2017.11.005Get rights and content

Highlights

  • Repeated GBCA injection is associated with T1 hyperintensity in the paediatric brain.

  • T1 hyperintensity is presumably due to gadolinium deposition.

  • Without exposure to intravenous GBCA, the dentate-to-pons signal intensity ratio may decrease with age.

  • A stable DN-P SI ratio across serial MR examinations could, theoretically, reflect gadolinium deposition in the dentate nucleus.

Aim

To determine whether repeated gadolinium-based contrast agent administration (GBCA) in children is associated with the development of increased T1-weighted signal intensity within the cerebellar dentate nucleus.

Materials and methods

With institutional review board approval for this The Health Insurance Portability and Accountability Act-compliant retrospective study, a cohort of 41 patients under the age of 18 years who underwent at least four contrast-enhanced magnetic resonance imaging (MR) examinations of the brain from 2005 to 2015 were identified. For each examination, both dentate nuclei were manually contoured, and the mean dentate nucleus-to-pons signal intensity (DN-P SI) ratio was calculated. The DN-P SI ratios from the last to first MRI examination were compared, and the correlation between DN-P SI ratio and cumulative gadolinium dose was calculated using a linear mixed effect model to control for potentially confounding variables.

Results

For the 41 patients in the cohort, there was a significant increase in the mean DN-P SI ratio from the first MRI to the last MRI examination (1.05 versus 1.11, p=0.004). After controlling for patient diagnosis, history of chemotherapy or radiation, sex, and age, there was a significant positive association between DN-P SI ratio and cumulative gadolinium dose (coefficient=0.401, p=0.032).

Conclusion

Repeated GBCA administration in children is associated with increased T1-weighted signal intensity within the dentate nucleus.

Introduction

It has recently been demonstrated that gadolinium-based contrast agent (GBCA) administration for clinical magnetic resonance imaging (MRI) can result in gadolinium deposition or retention in multiple organs, including the brain.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 Gadolinium deposition in the brain is associated with increased intrinsic signal intensity on T1-weighted images, which is most detectable in the globus pallidus and the cerebellar dentate nucleus. To date, most studies of brain gadolinium retention have been performed in adults with few studies of the paediatric brain. Although the clinical significance, if any, of brain gadolinium deposition or retention is uncertain, the paediatric brain could be more susceptible to the deleterious effects of gadolinium deposition because the paediatric brain is in general more vulnerable to a variety of toxins.12, 13 Additionally, the lifetime dose and duration of exposure to GBCA may be greater in children than adults. Initial studies documenting intracranial gadolinium deposition in adults focused on linear contrast agents, such as gadopentetate dimeglumine and gadodiamide.2, 4 Subsequent studies in adults have suggested that macrocyclic gadolinium-based contrast agents, such as gadoteridol and gadoterate meglumine, may be less likely to deposit within the brain in comparison to gadopentetate dimeglumine3, 6; however, Stojanov et al. found that the macrocyclic agent gadobutrol was associated with increasing T1-weighted hyperintensity within the dentate nucleus and globus pallidus.9 Thus, the nature of deposition of macrocyclic versus linear agents is currently unclear. Three recently published studies examining gadolinium deposition within the paediatric brain have focused exclusively on the linear agent gadopentetate dimeglumine.14, 15, 16

Gadolinium-enhanced MRI is an essential component of neuroimaging and clinical care in paediatric and adult patient populations. Thus, the aim of the present study was to investigate whether, as with adults, the paediatric brain shows imaging evidence of gadolinium retention following repeated exposure to a variety of GBCA.

Section snippets

Patients

With institutional review board approval for this HIPAA (Health Insurance Portability and Accountability Act)-compliant study and a waiver of informed consent, the institution's PACS (picture archiving and communication system) was queried to identify all patients under the age of 18 years who underwent a contrast-enhanced MRI of the brain performed at between the years of 2005 and 2015. From this query, a total of 247 patients were identified. Patients with fewer than four MRI examinations,

Patients

The present cohort was comprised of 25 male (61%) and 16 female (39%) paediatric patients under the age of 18 years (Table 1). On average (±standard deviation), each patient received 9.27±4.26 MRI examinations. Thirty-five of the patients (85%) had brain tumours. Eighteen of the patients (44%) had a history of chemotherapy, and six patients (15%) had a history of irradiation.

T1-hyperintensity within the dentate nuclei following repeated GBCA administration

For the 41 patients in the cohort, there was a significant increase in the DN-P SI ratio from the first MRI to the last

Discussion

The aim of the present study was to determine if T1-weighted signal intensity within the dentate nucleus increases in the paediatric brain following repeated GBCA administration, a phenomenon that has been well-documented in adults. For the cohort of 41 patients who received serial MRI examinations with GBCAs, the mean DN-P SI ratio significantly increased from the first MRI examination to the last MRI examination. A linear mixed effects model demonstrated that even after controlling for

References (17)

  • D.R. Roberts et al.

    Progressive increase of T1 signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MRI images in the paediatric brain exposed to multiple doses of gadolinium contrast

    Brain Dev

    (2016)
  • S.J. Blakemore

    Imaging brain development: the adolescent brain

    Neuroimage

    (2012)
  • Y. Errante et al.

    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

    (2014)
  • T. Kanda et al.

    High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MRI images: relationship with increasing cumulative dose of a gadolinium-based contrast material

    Radiology

    (2014)
  • T. Kanda et al.

    High signal intensity in dentate nucleus on unenhanced T1-weighted MRI images: association with linear versus macrocyclic gadolinium chelate administration

    Radiology

    (2015)
  • R.J. McDonald et al.

    Intracranial gadolinium deposition after contrast-enhanced MRI imaging

    Radiology

    (2015)
  • C.C. Quattrocchi et al.

    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

    (2015)
  • A. Radbruch et al.

    Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent

    Radiology

    (2015)
There are more references available in the full text version of this article.

Cited by (23)

  • Safety of Gadolinium Administration in Children

    2018, Pediatric Neurology
    Citation Excerpt :

    This was revealed through detection of T1 hyperintensity in the globus pallidus and dentate nucleus in children who had earlier doses of GBCA38–42[Table 2]. Additionally, numerous recent articles showed higher incidence of such hyperintensity in children receiving linear GBCA compared with its macrocyclic counterpart44-47 (Table 3). Histopathologic findings of brain biopsies offered confirmation of gadolinium deposition.49,50

View all citing articles on Scopus
1

These authors contributed equally to this study.

View full text