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August 06, 2019; 93 (6) Article

Cumulative gadodiamide administration leads to brain gadolinium deposition in early MS

Robert Zivadinov, Niels Bergsland, Jesper Hagemeier, Deepa P. Ramasamy, Michael G. Dwyer, Ferdinand Schweser, Channa Kolb, Bianca Weinstock-Guttman, David Hojnacki
First published July 8, 2019, DOI: https://doi.org/10.1212/WNL.0000000000007892
Robert Zivadinov
From the Buffalo Neuroimaging Analysis Center (R.Z., N.B., J.H., D.P.R.) and Jacobs Comprehensive MS Treatment and Research Center (C.K., B.W.-G., D.H.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z., M.G.D., F.S.), University at Buffalo, State University of New York.
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Niels Bergsland
From the Buffalo Neuroimaging Analysis Center (R.Z., N.B., J.H., D.P.R.) and Jacobs Comprehensive MS Treatment and Research Center (C.K., B.W.-G., D.H.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z., M.G.D., F.S.), University at Buffalo, State University of New York.
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Jesper Hagemeier
From the Buffalo Neuroimaging Analysis Center (R.Z., N.B., J.H., D.P.R.) and Jacobs Comprehensive MS Treatment and Research Center (C.K., B.W.-G., D.H.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z., M.G.D., F.S.), University at Buffalo, State University of New York.
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Deepa P. Ramasamy
From the Buffalo Neuroimaging Analysis Center (R.Z., N.B., J.H., D.P.R.) and Jacobs Comprehensive MS Treatment and Research Center (C.K., B.W.-G., D.H.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z., M.G.D., F.S.), University at Buffalo, State University of New York.
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Michael G. Dwyer
From the Buffalo Neuroimaging Analysis Center (R.Z., N.B., J.H., D.P.R.) and Jacobs Comprehensive MS Treatment and Research Center (C.K., B.W.-G., D.H.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z., M.G.D., F.S.), University at Buffalo, State University of New York.
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Ferdinand Schweser
From the Buffalo Neuroimaging Analysis Center (R.Z., N.B., J.H., D.P.R.) and Jacobs Comprehensive MS Treatment and Research Center (C.K., B.W.-G., D.H.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z., M.G.D., F.S.), University at Buffalo, State University of New York.
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Channa Kolb
From the Buffalo Neuroimaging Analysis Center (R.Z., N.B., J.H., D.P.R.) and Jacobs Comprehensive MS Treatment and Research Center (C.K., B.W.-G., D.H.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z., M.G.D., F.S.), University at Buffalo, State University of New York.
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Bianca Weinstock-Guttman
From the Buffalo Neuroimaging Analysis Center (R.Z., N.B., J.H., D.P.R.) and Jacobs Comprehensive MS Treatment and Research Center (C.K., B.W.-G., D.H.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z., M.G.D., F.S.), University at Buffalo, State University of New York.
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David Hojnacki
From the Buffalo Neuroimaging Analysis Center (R.Z., N.B., J.H., D.P.R.) and Jacobs Comprehensive MS Treatment and Research Center (C.K., B.W.-G., D.H.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z., M.G.D., F.S.), University at Buffalo, State University of New York.
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Citation
Cumulative gadodiamide administration leads to brain gadolinium deposition in early MS
Robert Zivadinov, Niels Bergsland, Jesper Hagemeier, Deepa P. Ramasamy, Michael G. Dwyer, Ferdinand Schweser, Channa Kolb, Bianca Weinstock-Guttman, David Hojnacki
Neurology Aug 2019, 93 (6) e611-e623; DOI: 10.1212/WNL.0000000000007892

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Abstract

Objective Frequent administration of gadolinium-based contrast agents in multiple sclerosis (MS) may increase signal intensity (SI) unenhanced T1-weighted imaging MRI throughout the brain. We evaluated the association between lifetime cumulative doses of gadodiamide administration and increased SI within the dentate nucleus (DN), globus pallidus (GP), and thalamus in patients with early MS.

Methods A total of 203 patients with MS (107 with baseline and follow-up MRI assessments) and 262 age- and sex-matched controls were included in this retrospective, longitudinal, 3T MRI-reader-blinded study. Patients with MS had disease duration <2 years at baseline and received exclusively gadodiamide at all MRI time points. SI ratio (SIR) to pons and CSF of lateral ventricle volume (CSF-LVV) were assessed. Analysis of covariance and correlation analyses, adjusted for age, sex, and region of interest volume, were used.

Results The mean follow-up time was 55.4 months, and the mean number of gadolinium-based contrast agents administrations was 9.2. At follow-up, 49.3% of patients with MS and no controls showed DN T1 hyperintensity (p < 0.001). The mean SIR of DN (p < 0.001) and of GP (p = 0.005) to pons and the mean SIR of DN, GP, and thalamus to CSF-LVV were higher in patients with MS compared to controls (p < 0.001). SIR of DN to pons was associated with number of gadodiamide doses (p < 0.001). No associations between SIR of DN, GP, and thalamus and clinical and MRI outcomes of disease severity were detected over the follow-up.

Conclusions DN, GP, and thalamus gadolinium deposition in early MS is associated with lifetime cumulative gadodiamide administration without clinical or radiologic correlates of more aggressive disease.

Glossary

ANT=
advanced normalization tool;
CI=
confidence interval;
CIS=
clinically isolated syndrome;
CSF-LVV=
CSF of lateral ventricle volume;
DN=
dentate nucleus;
FLAIR=
fluid-attenuated inversion recovery;
FOV=
field of view;
GBCA=
gadolinium-based contrast agents;
GM=
gray matter;
GP=
globus pallidus;
ICC=
intraclass correlation coefficient;
LV=
lesion volume;
MRF=
most recent follow-up;
MS=
multiple sclerosis;
ROI=
region of interest;
RRMS=
relapsing-remitting multiple sclerosis;
CSI=
signal intensity;
SIR=
signal intensity ratio;
TE=
echo time;
TI=
inversion time;
TR=
repetition time;
WI=
weighted images;
WM=
white matter

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 239

  • Podcast: NPub.org/uihdww

  • Received April 21, 2018.
  • Accepted in final form April 2, 2019.
  • © 2019 American Academy of Neurology
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