Skip to main content

Intravenous injection of gadobutrol in an epidemiological study group did not lead to a difference in relative signal intensities of certain brain structures after 5 years

An Erratum to this article was published on 21 June 2016



To investigate if application of macrocyclic gadolinium-based contrast agents in volunteers is associated with neuronal deposition detected by magnetic resonance imaging in a 5-year longitudinal survey.

Materials and methods

Three hundred eighty-seven volunteers who participated in a population-based study were enrolled. Subjects underwent plain T1-weighted brain MRI at baseline and 5 years later with identical sequence parameters. At baseline, 271 participants additionally received intravenous injection of the macrocyclic contrast agent gadobutrol (1.5 mmol/kg). A control group including 116 subjects received no contrast agent. Relative signal intensities of thalamus, pallidum, pons and dentate nucleus were compared at baseline and follow-up.


No difference in relative signal intensities was observed between contrast group (thalamus, p = 0.865; pallidum, p = 0.263; pons, p = 0.533; dentate nucleus, p = 0.396) and control group (thalamus, p = 0.683; pallidum; p = 0.970; pons, p = 0.773; dentate nucleus, p = 0.232) at both times. Comparison between both groups revealed no significant differences in relative signal intensities (thalamus, p = 0.413; pallidum, p = 0.653; pons, p = 0.460; dentate nucleus, p = 0.751). The study showed no significant change in globus pallidus-to-thalamus or dentate nucleus-to-pons ratios.


Five years after administration of a 1.5-fold dose gadobutrol to normal subjects, signal intensity of thalamus, pallidum, pons and dentate nucleus did not differ from participants who had not received gadobutrol.

Key Points

Gadobutrol does not lead to neuronal signal alterations after 5 years.

Neuronal deposition of macrocyclic contrast agent could not be confirmed.

Macrocyclic contrast agents in a proven dosage are safe.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. 1.

    Felix R, Schorner W, Laniado M et al (1985) Brain tumors: MR imaging with gadolinium-DTPA. Radiology 156:681–688

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Niendorf HP, Felix R, Laniado M, Schorner W, Kornmesser W, Claussen C (1986) Magnetic resonance imaging of intracranial tumors using gadolinium-DTPA. Initial experience with fast imaging. Acta Radiol Suppl 369:561–563

    CAS  PubMed  Google Scholar 

  3. 3.

    Claussen C, Laniado M, Schorner W et al (1985) Gadolinium-DTPA in MR imaging of glioblastomas and intracranial metastases. AJNR Am J Neuroradiol 6:669–674

    CAS  PubMed  Google Scholar 

  4. 4.

    Weinmann HJ, Brasch RC, Press WR, Wesbey GE (1984) Characteristics of gadolinium-DTPA complex: a potential NMR contrast agent. AJR Am J Roentgenol 142:619–624

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Port M, Idee JM, Medina C, Robic C, Sabatou M, Corot C (2008) Efficiency, thermodynamic and kinetic stability of marketed gadolinium chelates and their possible clinical consequences: a critical review. Biometals 21:469–490

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Frenzel T, Lengsfeld P, Schirmer H, Hutter J, Weinmann HJ (2008) Stability of gadolinium-based magnetic resonance imaging contrast agents in human serum at 37 degrees C. Investig Radiol 43:817–828

    CAS  Article  Google Scholar 

  7. 7.

    Hao D, Ai T, Goerner F, Hu X, Runge VM, Tweedle M (2012) MRI contrast agents: basic chemistry and safety. J Magn Reson Imaging 36:1060–1071

    Article  PubMed  Google Scholar 

  8. 8.

    Grobner T (2006) Gadolinium--a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 21:1104–1108

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Marckmann P, Skov L, Rossen K et al (2006) Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 17:2359–2362

    Article  PubMed  Google Scholar 

  10. 10.

    Kanal E, Tweedle MF (2015) Residual or retained gadolinium: practical implications for radiologists and our patients. Radiology 275:630–634

    Article  PubMed  Google Scholar 

  11. 11.

    Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D (2014) High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material. Radiology 270:834–841

    Article  PubMed  Google Scholar 

  12. 12.

    Kanda T, Fukusato T, Matsuda M et al (2015) Gadolinium-based contrast agent accumulates in the brain even in subjects without severe renal dysfunction: evaluation of autopsy brain specimens with inductively coupled plasma mass spectroscopy. Radiology 276:228–232

    Article  PubMed  Google Scholar 

  13. 13.

    Errante Y, Cirimele V, Mallio CA, Di Lazzaro V, Zobel BB, Quattrocchi CC (2014) 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. Investig Radiol 49:685–690

    CAS  Article  Google Scholar 

  14. 14.

    McDonald RJ, McDonald JS, Kallmes DF et al (2015) Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology 275:772–782

    Article  PubMed  Google Scholar 

  15. 15.

    Volzke H, Alte D, Schmidt CO et al (2011) Cohort profile: the study of health in Pomerania. Int J Epidemiol 40:294–307

    Article  PubMed  Google Scholar 

  16. 16.

    John U, Greiner B, Hensel E et al (2001) Study of health in pomerania (SHIP): a health examination survey in an east German region: objectives and design. Soz Praventivmed 46:186–194

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Hegenscheid K, Kuhn JP, Volzke H, Biffar R, Hosten N, Puls R (2009) Whole-body magnetic resonance imaging of healthy volunteers: pilot study results from the population-based SHIP study. Röfo 181:748–759

    CAS  PubMed  Google Scholar 

  18. 18.

    Radbruch A, Weberling LD, Kieslich PJ et al (2015) Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent. Radiology 275:783–791

    Article  PubMed  Google Scholar 

  19. 19.

    Kanda T, Osawa M, Oba H et al (2015) High signal intensity in dentate nucleus on unenhanced T1-weighted MR images: association with linear versus macrocyclic gadolinium chelate administration. Radiology 275:803–809

    Article  PubMed  Google Scholar 

  20. 20.

    Radbruch A, Weberling LD, Kieslich PJ et al (2015) High-signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted images: evaluation of the macrocyclic gadolinium-based contrast agent gadobutrol. Investig Radiol 50:805–810

    CAS  Article  Google Scholar 

  21. 21.

    Kasahara S, Miki Y, Kanagaki M et al (2011) Hyperintense dentate nucleus on unenhanced T1-weighted MR images is associated with a history of brain irradiation. Radiology 258:222–228

    Article  PubMed  Google Scholar 

  22. 22.

    Roccatagliata L, Vuolo L, Bonzano L, Pichiecchio A, Mancardi GL (2009) Multiple sclerosis: hyperintense dentate nucleus on unenhanced T1-weighted MR images is associated with the secondary progressive subtype. Radiology 251:503–510

    Article  PubMed  Google Scholar 

  23. 23.

    Lai PH, Chen C, Liang HL, Pan HB (1999) Hyperintense basal ganglia on T1-weighted MR imaging. AJR Am J Roentgenol 172:1109–1115

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Rovira A, Alonso J, Cordoba J (2008) MR imaging findings in hepatic encephalopathy. AJNR Am J Neuroradiol 29:1612–1621

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Oikonomou A, Chatzistefanou A, Zezos P, Mintzopoulou P, Vadikolias K, Prassopoulos P (2012) Basal ganglia hyperintensity on T1-weighted MRI in Rendu-Osler-Weber disease. J Magn Reson Imaging 35:426–430

    Article  PubMed  Google Scholar 

  26. 26.

    Valdes Hernandez Mdel C, Maconick LC, Tan EM, Wardlaw JM (2012) Identification of mineral deposits in the brain on radiological images: a systematic review. Eur Radiol 22:2371–2381

    Article  PubMed  Google Scholar 

  27. 27.

    Shin YC, Kim E, Cheong HK et al (2007) High signal intensity on magnetic resonance imaging as a predictor of neurobehavioral performance of workers exposed to manganese. Neurotoxicology 28:257–262

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    da Silva CJ, da Rocha AJ, Jeronymo S et al (2007) A preliminary study revealing a new association in patients undergoing maintenance hemodialysis: manganism symptoms and T1 hyperintense changes in the basal ganglia. AJNR Am J Neuroradiol 28:1474–1479

    Article  PubMed  Google Scholar 

  29. 29.

    Martin-Duverneuil N, Idbaih A, Hoang-Xuan K et al (2006) MRI features of neurodegenerative Langerhans cell histiocytosis. Eur Radiol 16:2074–2082

    CAS  Article  PubMed  Google Scholar 

Download references


The scientific guarantor of this publication is MD J.-P. Kühn. The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. This study has received funding by the Federal Ministry of Education and Research (01ZZ9603, 01ZZ0103, 01ZZ0403, 01ZZ0701, 03ZIK012), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Whole-body MR imaging was supported by a joint grant from Siemens Healthcare, Erlangen, Germany, and the Federal State of Mecklenburg-West Pomerania. The University of Greifswald is a member of the ‘Center of Knowledge Interchange’ program of Siemens AG. Contrast-enhanced MRI research is part of the entire whole-body MRI study and was supported by Bayer Healthcare. One of the authors has significant statistical expertise. Institutional Review Board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. Some study subjects or cohorts have been previously reported in the context of publications made during the Study of Health in Pomerania, a prospective population-based cohort study in a defined region in Northeast Germany. Methodology: retrospective, observational, performed at one institution.

Author information



Corresponding author

Correspondence to Marie-Luise Kromrey.

Additional information

An erratum to this article is available at

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kromrey, ML., Liedtke, K.R., Ittermann, T. et al. Intravenous injection of gadobutrol in an epidemiological study group did not lead to a difference in relative signal intensities of certain brain structures after 5 years. Eur Radiol 27, 772–777 (2017).

Download citation


  • Gadolinium
  • Magnetic resonance imaging
  • Contrast media
  • Brain
  • Gadobutrol