Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Japanese Journal of Radiology
Published in: Japanese Journal of Radiology 1/2016

01-01-2016 | Review

Brain gadolinium deposition after administration of gadolinium-based contrast agents

Authors: Tomonori Kanda, Hiroshi Oba, Keiko Toyoda, Kazuhiro Kitajima, Shigeru Furui

Published in: Japanese Journal of Radiology | Issue 1/2016

Login to get access

Abstract

Gadolinium-based contrast agents (GBCAs) consist of gadolinium ions and a chelating agent that binds the gadolinium ion tightly so that its toxicity is not manifested. However, in 2013, an association between brain MRI abnormalities and a history of GBCA administration was first reported. Even in patients with normal renal function, increased signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted images showed a positive correlation with previous exposure to linear chelate type GBCAs, but not to macrocyclic chelate type ones. This difference of GBCAs is speculated to reflect the stability of GBCAs, and de-chelated gadolinium deposition has been strongly suspected. Using inductively coupled plasma mass spectroscopy, gadolinium was detected from patients’ brains with a history of repeated GBCA administration. In some cases, the gadolinium concentration of a patient’s brain with normal renal function exceeded the gadolinium concentration of the skin in nephrogenic systemic fibrosis patients, but without any histological change. The actual risk has not been documented yet, but it seems important to consider the potential unknown risks of residual gadolinium in our decisions regarding GBCA administration, and to make efforts to minimize any residual gadolinium in the patient’s body.
Literature
1.
2.
Thomsen HS, Morcos SK, Almén T, Bellin MF, Bertolotto M, Bongartz G, et al. Nephrogenic systemic fibrosis and gadolinium-based contrast media: updated ESUR Contrast Medium Safety Committee guidelines. Eur Radiol. 2013;23:307–18.CrossRefPubMed
3.
Runge VM, Ai T, Hao D, Hu X. The developmental history of the gadolinium chelates as intravenous contrast media for magnetic resonance. Invest Radiol. 2011;46:807–16.CrossRefPubMed
4.
Runge VM, Stewart RG, Clanton JA, Jones MM, Lukehart CM, Partain CL, et al. Work in progress: potential oral and intravenous paramagnetic NMR contrast agents. Radiology. 1983;147:789–91.CrossRefPubMed
5.
Hao D, Ai T, Goerner F, Hu X, Runge VM, Tweedle M. MRI contrast agents: basic chemistry and safety. J Magn Reson Imaging. 2012;36:1060–71.CrossRefPubMed
6.
Port M, Idée JM, Medina C, et al. Efficiency, thermodynamic and kinetic stability of marketed gadolinium chelates and their possible clinical consequences: a critical review. Biometals. 2008;21:469–90.CrossRefPubMed
7.
Idée JM, Port M, Robic C, et al. Role of thermodynamic and kinetic parameters in gadolinium chelate stability. J Magn Reson Imaging. 2009;30:1249–58.CrossRefPubMed
8.
Wedeking P, Tweedle M. Comparison of the biodistribution of 153Gd-labeled Gd(DTPA)2-, Gd(DOTA)-, and Gd(acetate)n in mice. Int J Radiat Appl Instrum B. 1988;15:395–402.CrossRef
9.
Wedeking P, Kumar K, Tweedle MF. Dissociation of gadolinium chelates in mice: relationship to chemical characteristics. Magn Reson Imaging. 1992;10:641–8.CrossRefPubMed
10.
Wedeking P, Kumar K, Tweedle MF. Dose-dependent biodistribution of [153Gd]Gd(acetate)n in mice. Nucl Med Biol. 1993;20:679–91.CrossRefPubMed
11.
Tweedle MF, Wedeking P, Kumar K. Biodistribution of radiolabeled, formulated gadopentetate, gadoteridol, gadoterate, and gadodiamide in mice and rats. Invest Radiol. 1995;30:372–80.CrossRefPubMed
12.
Sieber MA, Lengsfeld P, Frenzel T, Golfier S, Schmitt-Willich H, Siegmund F, 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;18:2164–73.CrossRefPubMed
13.
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;39:138–42.CrossRefPubMed
14.
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;41:272–8.CrossRefPubMed
15.
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;1:479–88.CrossRefPubMed
16.
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;51:1126–36.CrossRefPubMed
17.
Frenzel T, Lengsfeld P, Schirmer H, Hütter J, Weinmann HJ. Stability of gadolinium-based magnetic resonance imaging contrast agents in human serum at 37 °C. Invest Radiol. 2008;43:817–28.CrossRefPubMed
18.
Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE. Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet. 2000;356:1000–1.CrossRefPubMed
19.
Grobner T. Gadolinium—a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant. 2006;21:1104–8.CrossRefPubMed
20.
Marckmann P, Skov L, Rossen K, Dupont A, Damholt MB, Heaf JG, et al. Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol. 2006;17:2359–62.CrossRefPubMed
21.
Boyd AS, Zic JA, Abraham JL. Gadolinium deposition in nephrogenic fibrosing dermopathy. J Am Acad Dermatol. 2007;56:27–30.CrossRefPubMed
22.
High WA, Ayers RA, Chandler J, Zito G, Cowper SE. Gadolinium is detectable within the tissue of patients with nephrogenic systemic fibrosis. Am Acad Dermatol. 2007;56:21–6.CrossRef
23.
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;64:91–6.CrossRefPubMed
24.
25.
Khawaja AZ, Cassidy DB, Shakarchi J, McGrogan DG, Inston NG, Jones RG. Revisiting the risks of MRI with Gadolinium based contrast agents-review of literature and guidelines. Insights Imaging. 2015;6:553–8.PubMedCentralCrossRefPubMed
26.
Sadowski EA, Bennett LK, Chan MR, Wentland AL, Garrett AL, Garrett RW, et al. Nephrogenic systemic fibrosis: risk factors and incidence estimation. Radiology. 2007;243:148–57.CrossRefPubMed
27.
28.
Heverhagen JT, Krombach GA, Gizewski E. Application of extracellular gadolinium-based MRI contrast agents and the risk of nephrogenic systemic fibrosis. RöFo Fortschr Roentgenstr. 2014;186:661–9.CrossRef
29.
European Society of Urogenital Radiology (ESUR). ESUR guidelines on contrast media version 9.0. Vienna: ESUR Head Office; 2014. p. 16–8.
30.
31.
Kanda T, Kawaguchi H. Hyperintense dentate nucleus and globus pallidus on unenhanced T1-weighted MR images are associated with gadolinium-based contrast media. Neuroradiol. 2013;55:1268–9.
32.
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;270:834–41.CrossRefPubMed
33.
Roccatagliata L, Vuolo L, Bonzano L, Pichiecchio A, Mancardi GL. Multiple sclerosis: hyperintense dentate nucleus on unenhanced T1-weighted MR images is associated with the secondary progressive subtype. Radiology. 2009;251:503–10.CrossRefPubMed
34.
Kasahara S, Miki Y, Kanagaki M, Yamamoto A, Mori N, Sawada T, et al. Hyperintense dentate nucleus on unenhanced T1-weighted MR images is associated with a history of brain irradiation. Radiology. 2011;258:222–8.CrossRefPubMed
35.
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;49:685–90.CrossRefPubMed
36.
Quattrocchi CC, Mallio CA, Errante Y, Cirimele V, Carideo L, Ax A, et al. Gadodiamide and dentate nucleus T1 hyperintensity in patients with meningioma evaluated by multiple follow-up contrast-enhanced magnetic resonance examinations with no systemic interval therapy. Invest Radiol. 2015;50:470–2.CrossRefPubMed
37.
Adin ME, Kleinberg L, Vaidya D, Zan E, Mirbagheri S, Yousem DM. Hyperintense dentate nuclei on T1-weighted MRI: relation to repeat gadolinium administration. AJNR Am J Neuroradiol. 2015;36(10):1859–65. doi:10.​3174/​ajnr.​A4378.CrossRefPubMed
38.
Roberts DR, Holden KR. Progressive increase of T1 signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images in the pediatric brain exposed to multiple doses of gadolinium contrast. Brain Dev. 2015. doi:10.​1016/​j.​braindev.​2015.​08.​009.PubMed
39.
Kanda T, Osawa M, Oba H, Toyoda K, Kotoku J, Haruyama T, et al. High signal intensity in dentate nucleus on unenhanced T1-weighted MR images: association with linear versus macrocyclic gadolinium chelate administration. Radiology. 2015;275:803–9.CrossRefPubMed
40.
Radbruch A, Weberling LD, Kieslich PJ, Eidel O, Burth S, Kickingereder P, et al. Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent. Radiology. 2015;275:783–91.CrossRefPubMed
41.
Nandwana SB, Moreno CC, Osipow MT, Sekhar A, Cox KL. Gadobenate dimeglumine administration and nephrogenic systemic fibrosis: is there a real risk in patients with impaired renal function? Radiology. 2015;276:741–7.CrossRefPubMed
42.
Ramalho J, Castillo M, AlObaidy M, Nunes RH, Ramalho M, Dale BM, et al. High signal intensity in globus pallidus and dentate nucleus on unenhanced T1-weighted MR images: evaluation of two linear gadolinium-based contrast agents. Radiology. 2015;276:836–44.CrossRefPubMed
43.
44.
Stojanov DA, Aracki-Trenkic A, Vojinovic S, Benedeto-Stojanov D, Ljubisavljevic S, et al. Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol. Eur Radiol. 2015. doi:10.​1007/​s00330-015-3879-9.
45.
Agris J, Pietsch H, Balzer T. What evidence is there that gadobutrol causes increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W MRI in patients with RRMS? Eur Radiol. 2015. doi:10.​1007/​s00330-015-4019-2.PubMed
46.
Radbruch A, Weberling LD, Kieslich PJ, et al. High-signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted images: evaluation of the macrocyclic gadolinium-based contrast agent gadobutrol. Invest Radiol. 2015;50(12):805–10. doi:10.​1097/​RLI.​0000000000000227​.CrossRefPubMed
47.
Ginat DT, Meyers SP. Intracranial lesions with high signal intensity on T1-weighted MR images: differential diagnosis. Radiographics. 2012;32:499–516.CrossRefPubMed
48.
McDonald RJ, McDonald JS, Kallmes DF, Jentoft ME, Murray DL, Thielen KR, et al. Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology. 2015;275:772–82.CrossRefPubMed
49.
Kanda T, Fukusato T, Matsuda M, Toyoda K, Oba H, Kotoku J, et al. 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. 2015;276:228–32.CrossRefPubMed
50.
Robert P, Lehericy S, Grand S, Violas X, Fretellier N, Idée JM, et al. T1-weighted hypersignal in the deep cerebellar nuclei after repeated administrations of gadolinium-based contrast agents in healthy rats: difference between linear and macrocyclic agents. Invest Radiol. 2015;50:473–80.PubMedCentralCrossRefPubMed
51.
Runge VM. Commentary on T1-weighted hypersignal in the deep cerebellar nuclei after repeated administrations of gadolinium-based contrast agents in healthy rats: difference between linear and macrocyclic agents. Invest Radiol. 2015;50:481–2.CrossRefPubMed
52.
Frenzel T, Lengsfeld P, Schirmer H, Hütter J, Weinmann HJ. Stability of gadolinium-based magnetic resonance imaging contrast agents in human serum at 37 °C. Invest Radiol. 2008;43:817–28.CrossRefPubMed
53.
Puttagunta NR, Gibby WA, Smith GT. Human in vivo comparative study of zinc and copper transmetallation after administration of magnetic resonance imaging contrast agents. Invest Radiol. 1996;31:739–42.CrossRefPubMed
54.
Kimura J, Ishiguchi T, Matsuda J, Ohno R, Nakamura A, Kamei S, et al. Human comparative study of zinc and copper excretion via urine after administration of magnetic resonance imaging contrast agents. Radiat Med. 2005;23:322–6.PubMed
55.
Yamada M, Asano T, Okamoto K, Hayashi Y, Kanematsu M, Hoshi H, et al. High frequency of calcification in basal ganglia on brain computed tomography images in Japanese older adults. Geriatr Gerontol Int. 2013;13:706–10.CrossRefPubMed
56.
Valdés Hernández Mdel C, Maconick LC, Tan EM, Wardlaw JM. Identification of mineral deposits in the brain on radiological images: a systematic review. Eur Radiol. 2012;22:2371–81.CrossRefPubMed
57.
Bressler JP, Olivi L, Cheong JH, Kim Y, Maerten A, Bannon D. Metal transporters in intestine and brain: their involvement in metal-associated neurotoxicities. Hum Exp Toxicol. 2007;26:221–9.CrossRefPubMed
58.
Kanda T, Matsuda M, Oba H, et al. High T1 signal intensity in dentate nucleus after multiple injections of linear gadolinium chelates response. Radiology. 2015;276:616–7.CrossRefPubMed
59.
Gathings RM, Reddy R, Santa Cruz D, Brodell RT. Gadolinium-associated plaques: a new, distinctive clinical entity. JAMA Dermatol. 2015;151:316–9.CrossRefPubMed
60.
Kartono F, Basile A, Roshdieh B, Schwimer C, Shitabata PK. Findings of osseous sclerotic bodies: a unique sequence of cutaneous bone formation in nephrogenic systemic fibrosis. J Cutan Pathol. 2011;38:286–9.CrossRefPubMed
61.
Bhawan J, Swick BL, Koff AB, Stone MS. Sclerotic bodies in nephrogenic systemic fibrosis: a new histopathologic finding. J Cutan Pathol. 2009;36:548–52.CrossRefPubMed
62.
Grekin SJ, Holcomb MJ, Modi GM, Huttenbach YT, Poythress EL, Diwan AH. Lollipop lesions in nephrogenic systemic fibrosis mimicking a deep fungal infection. J Cutan Pathol. 2012;39:981–4.CrossRefPubMed
63.
Kanal E, Tweedle MF. Residual or retained gadolinium: practical implications for radiologists and our patients. Radiology. 2015;275:630–4.CrossRefPubMed
64.
65.
Japan Radiological Society and Japanese Society of Nephrology: guidelines for administering gadolinium based contrast agents to patients with renal dysfunction. Japan Radiological Society web site. http://​www.​radiology.​jp/​content/​files/​743.​pdf. Published 25 July 2008. Updated 2 September 2009. Accessed 28 July 2015.
Metadata
Title
Brain gadolinium deposition after administration of gadolinium-based contrast agents
Authors
Tomonori Kanda
Hiroshi Oba
Keiko Toyoda
Kazuhiro Kitajima
Shigeru Furui
Publication date
01-01-2016
Publisher
Springer Japan
Published in
Japanese Journal of Radiology / Issue 1/2016
Print ISSN: 1867-1071
Electronic ISSN: 1867-108X
DOI
https://doi.org/10.1007/s11604-015-0503-5

Other articles of this Issue 1/2016

Japanese Journal of Radiology 1/2016 Go to the issue

Original Article

Chemoradiotherapy for patients with recurrent lymph-node metastasis or local recurrence of gastric cancer after curative gastrectomy

Editorial

New Year's resolution: increase the impact factor of this journal

Special Report

The Practice Guidelines for Primary Care of Acute Abdomen 2015

Special Report

The essence of the Japan Radiological Society/Japanese College of Radiology Imaging Guideline

Original Article

Evaluation of diagnostic accuracy in CT perfusion analysis in moyamoya disease

Original Article

Multicenter study of quantitative computed tomography analysis using a computer-aided three-dimensional system in patients with idiopathic pulmonary fibrosis