Cumulative gadodiamide administration leads to brain gadolinium deposition in early MS

Neurology. 2019 Aug 6;93(6):e611-e623. doi: 10.1212/WNL.0000000000007892. Epub 2019 Jul 8.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Contrast Media / pharmacokinetics*
  • Female
  • Follow-Up Studies
  • Gadolinium / metabolism*
  • Gadolinium DTPA / pharmacokinetics*
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnostic imaging
  • Multiple Sclerosis / metabolism*
  • Retrospective Studies


  • Contrast Media
  • gadodiamide
  • Gadolinium
  • Gadolinium DTPA