Even in subjects without severe renal dysfunction, gadolinium-based contrast agent administration causes gadolinium accumulation in the brain, especially in the dentate nucleus and globus pallidus.


To use inductively coupled plasma mass spectroscopy (ICP-MS) to evaluate gadolinium accumulation in brain tissues, including the dentate nucleus (DN) and globus pallidus (GP), in subjects who received a gadolinium-based contrast agent (GBCA).

Materials and Methods

Institutional review board approval was obtained for this study. Written informed consent for postmortem investigation was obtained either from the subject prior to his or her death or afterward from the subject’s relatives. Brain tissues obtained at autopsy in five subjects who received a linear GBCA (GBCA group) and five subjects with no history of GBCA administration (non-GBCA group) were examined with ICP-MS. Formalin-fixed DN tissue, the inner segment of the GP, cerebellar white matter, the frontal lobe cortex, and frontal lobe white matter were obtained, and their gadolinium concentrations were measured. None of the subjects had received a diagnosis of severely compromised renal function (estimated glomerular filtration rate <45 mL/min/1.73 m2) or acute renal failure. Fisher permutation test was used to compare gadolinium concentrations between the two groups and among brain regions.


Gadolinium was detected in all specimens in the GBCA agent group (mean, 0.25 µg per gram of brain tissue ± 0.44 [standard deviation]), with significantly higher concentrations in each region (P = .004 vs the non-GBCA group for all regions). In the GBCA group, the DN and GP showed significantly higher gadolinium concentrations (mean, 0.44 µg/g ± 0.63) than other regions (0.12 µg/g ± 0.16) (P = .029).


Even in subjects without severe renal dysfunction, GBCA administration causes gadolinium accumulation in the brain, especially in the DN and GP.

© RSNA, 2015


  • 1. Hao D, Ai T, Goerner F, Hu X, Runge VM, Tweedle M. MRI contrast agents: basic chemistry and safety. J Magn Reson Imaging 2012;36(5):1060–1071. Crossref, MedlineGoogle Scholar
  • 2. Runge VM. Safety of approved MR contrast media for intravenous injection. J Magn Reson Imaging 2000;12(2):205–213. Crossref, MedlineGoogle Scholar
  • 3. Idée JM, Port M, Robic C, Medina C, Sabatou M, Corot C. Role of thermodynamic and kinetic parameters in gadolinium chelate stability. J Magn Reson Imaging 2009;30(6):1249–1258. Crossref, MedlineGoogle Scholar
  • 4. Aime S, Caravan P. Biodistribution of gadolinium-based contrast agents, including gadolinium deposition. J Magn Reson Imaging 2009;30(6):1259–1267. Crossref, MedlineGoogle Scholar
  • 5. Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D. 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 2014;270(3):834–841. LinkGoogle Scholar
  • 6. Kanda T, Osawa M, Oba H, et al. High signal intensity in dentate nucleus on unenhanced T1-weighted MR images: association with linear versus macrocyclic gadolinium chelate administration. Radiology 2015 Jan 27:140364. [Epub ahead of print] LinkGoogle Scholar
  • 7. Errante Y, Cirimele V, Mallio CA, Di Lazzaro V, Zobel BB, Quattrocchi CC. 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. Invest Radiol 2014;49(10):685–690. Crossref, MedlineGoogle Scholar
  • 8. Sanyal S, Marckmann P, Scherer S, Abraham JL. Multiorgan gadolinium (Gd) deposition and fibrosis in a patient with nephrogenic systemic fibrosis: an autopsy-based review. Nephrol Dial Transplant 2011;26(11):3616–3626. Crossref, MedlineGoogle Scholar
  • 9. Christensen KN, Lee CU, Hanley MM, Leung N, Moyer TP, Pittelkow MR. Quantification of gadolinium in fresh skin and serum samples from patients with nephrogenic systemic fibrosis. J Am Acad Dermatol 2011;64(1):91–96. Crossref, MedlineGoogle Scholar
  • 10. Gibby WA, Gibby KA, Gibby WA. Comparison of Gd DTPA-BMA (Omniscan) versus Gd HP-DO3A (ProHance) retention in human bone tissue by inductively coupled plasma atomic emission spectroscopy. Invest Radiol 2004;39(3):138–142. Crossref, MedlineGoogle Scholar
  • 11. White GW, Gibby WA, Tweedle MF. Comparison of Gd(DTPA-BMA) (Omniscan) versus Gd(HP-DO3A) (ProHance) relative to gadolinium retention in human bone tissue by inductively coupled plasma mass spectroscopy. Invest Radiol 2006;41(3):272–278. Crossref, MedlineGoogle Scholar
  • 12. Darrah TH, Prutsman-Pfeiffer JJ, Poreda RJ, Ellen Campbell M, Hauschka PV, Hannigan RE. Incorporation of excess gadolinium into human bone from medical contrast agents. Metallomics 2009;1(6):479–488. Crossref, MedlineGoogle Scholar
  • 13. Xia D, Davis RL, Crawford JA, Abraham JL. Gadolinium released from MR contrast agents is deposited in brain tumors: in situ demonstration using scanning electron microscopy with energy dispersive X-ray spectroscopy. Acta Radiol 2010;51(10):1126–1136. Crossref, MedlineGoogle Scholar
  • 14. McDonald RJ, McDonald JS, Kallmes DF, et al. Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology 2015 Mar 5:150025. [Epub ahead of print] LinkGoogle Scholar
  • 15. Sieber MA, Lengsfeld P, Frenzel T, et al. Preclinical investigation to compare different gadolinium-based contrast agents regarding their propensity to release gadolinium in vivo and to trigger nephrogenic systemic fibrosis-like lesions. Eur Radiol 2008;18(10):2164–2173. Crossref, MedlineGoogle Scholar
  • 16. Sieber MA, Pietsch H, Walter J, Haider W, Frenzel T, Weinmann HJ. A preclinical study to investigate the development of nephrogenic systemic fibrosis: a possible role for gadolinium-based contrast media. Invest Radiol 2008;43(1):65–75. Crossref, MedlineGoogle Scholar

Article History

Received November 20, 2014; revision requested January 5, 2015; revision received February 8; accepted March 2; final version accepted March 24.
Published online: May 05 2015
Published in print: July 2015