title: Repeated intravenous administration of gadobutrol does not lead to increased signal intensity on unenhanced T1-weighted images-a voxel-based whole brain analysis.
abstract: OBJECTIVE
  To identify a possible association between repeated intravenous administration of gadobutrol and increased signal intensity in the grey and white matter using voxel-based whole-brain analysis.
  
  
  METHODS
  In this retrospective single-centre study, 217 patients with a clinically isolated syndrome underwent baseline brain magnetic resonance imaging and at least one annual follow-up examination with intravenous administration of 0.1 mmol/kg body weight of gadobutrol. Using the "Diffeomorphic Anatomical Registration using Exponentiated Lie algebra" (DARTEL) normalisation process, tissue templates for grey matter (GM), white matter (WM), and cerebrospinal fluid (CSF) were calculated, as were GM-CSF and WM-CSF ratios. Voxel-based whole-brain analysis was used to calculate the signal intensity for each voxel in each data set. Paired t-test was applied to test differences to baseline MRI for significance.
  
  
  RESULTS
  Voxel-based whole-brain analysis demonstrated no significant changes in signal intensity of grey and white matter after up to five gadobutrol administrations. There was no significant change in GM-CSF and grey WM-CSF ratios.
  
  
  CONCLUSIONS
  Voxel-based whole-brain analysis did not demonstrate increased signal intensity of GM and WM on unenhanced T1-weighted images after repeated gadobutrol administration. The molecular structure of gadolinium-based contrast agent preparations may be an essential factor causing SI increase on unenhanced T1-weighted images.
  
  
  CONCLUSIONS
  • Repeated administration of gadobutrol does not lead to increased signal intensity. • Voxel-based whole-brain analysis allows assessment of subtle changes in signal intensity. • Macrocyclic contrast agents in a proven dosage are safe.
authors.affiliation: Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany. soenke.langner@uni-greifswald.de.
authors.forename: Soenke
authors.identifier: http://orcid.org/0000-0001-7241-1173
authors.initials: S
authors.lastname: Langner
authors.affiliation: Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany.
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Kromrey
authors.affiliation: Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany.|Institute for Radiology, University Hospital, Carl Gustav Carus University Dresden, Dresden, Germany.
authors.forename: Jens-Peter
authors.initials: JP
authors.lastname: Kuehn
authors.affiliation: Department of Neurology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, Greifswald, 17475, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Grothe
authors.affiliation: Functional Imaging Unit, Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, Greifswald, 17475, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Domin
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D001927:Brain Diseases / Q000000981:diagnostic imaging*; D002529:Cerebellar Nuclei / Q000473:pathology; D003287:Contrast Media / Q000008:administration & dosage*; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000008:administration & dosage*; D012189:Retrospective Studies; D066127:White Matter / Q000000981:diagnostic imaging
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; C090600:gadobutrol
keywords: Brain; Contrast media; Gadolinium; MRI; Multiple sclerosis