Effect of Long-Term Retention of Gadolinium on Metabolism of Deep Cerebellar Nuclei After Repeated Injections of Gadodiamide in Rats - Université d'Orléans Access content directly
Journal Articles Investigative Radiology Year : 2020

Effect of Long-Term Retention of Gadolinium on Metabolism of Deep Cerebellar Nuclei After Repeated Injections of Gadodiamide in Rats

Véronique Vives
  • Function : Author
Rebecca Buchholz
  • Function : Author
William Même
Cécile Factor
  • Function : Author
Stefanie Fingerhut
  • Function : Author
Michael Sperling
  • Function : Author
Uwe Kärst
  • Function : Author
  • PersonId : 929157
Philippe Robert
S. Même

Abstract

OBJECTIVES:The aim of this study was to determine potential metabolism and histological modifications due to gadolinium retention within deep cerebellar nuclei (DCN) after linear gadolinium-based contrast agent injection (gadodiamide) in rats at 1 year after the last injection.MATERIALS AND METHODS:Twenty female rats received 20 doses of gadodiamide (0.6 mmol of gadolinium per kilogram each) over 5 weeks. They were followed at 1 week (M0), 6 weeks (M1), and 54 to 55 weeks (M13) postinjections to evaluate hypersignal on unenhanced T1-weighted magnetic resonance imaging and metabolic alterations by H magnetic resonance spectroscopy (H-MRS). At 1 year postinjections, brains were sampled to determine the localization of gadolinium within cerebellum by laser ablation inductively coupled mass spectroscopy and to evaluate morphological changes by semiquantitative immunofluorescence analysis.RESULTS:There is a significant increase of the ratio DCN/brainstem for the gadodiamide group at M0 (+7.2% vs control group = 0.989 ± 0.01), M1 (+7.6% vs control group = 1.002 ± 0.018), and it lasted up to M13 (+4.7% vs control group = 0.9862 ± 0.008). No variation among metabolic markers (cellular homeostasis [creatine, choline, taurine], excitatory neurotransmitter [glutamate], and metabolites specific to a cellular compartment [N-acetyl aspartate for neurons and myo-inositol for glial cells]) were detected by H-MRS between gadodiamide and saline groups at M0, M1, and M13. At M13, laser ablation inductively coupled mass spectroscopy demonstrated that long-term gadolinium retention occurred preferentially in DCN. No histological abnormalities (including analysis of astrocytes, neurons, and microglial cells) were found in the rostral part of DCN.CONCLUSIONS:Repeated administration of gadodiamide lead to a retention of gadolinium preferentially within DCN at 1 year postinjections. This retention did not lead to any detectable changes of the measured metabolic biomarkers nor histological alterations.

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Imaging
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hal-02437163 , version 1 (16-11-2020)

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Dounia El Hamrani, Véronique Vives, Rebecca Buchholz, William Même, Cécile Factor, et al.. Effect of Long-Term Retention of Gadolinium on Metabolism of Deep Cerebellar Nuclei After Repeated Injections of Gadodiamide in Rats. Investigative Radiology, 2020, 55 (2), pp.120-128. ⟨10.1097/RLI.0000000000000621⟩. ⟨hal-02437163⟩
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