Cumulative administrations of gadolinium-based contrast agents: risks of accumulation and toxicity of linear vs macrocyclic agents

References

• Aylett BJ. 1985. Chemistry of the elements. Oxford: Butterworth-Heinemann Available from: http://linkinghub.elsevier.com/retrieve/pii/S0277538700841807
   Google Scholar
• Azim NH, Subki A, Norhana Z, Yusof B. 2018. Abiotic stresses induce total phenolic, total flavonoid and antioxidant properties in Malaysian indigenous microalgae and cyanobacterium. Malays J Microbiol. 14:25–33.
   Web of Science ®Google Scholar
• Bae S, Lee HJ, Han K, Park YW, Choi YS, Ahn SS, Kim J, Lee SK. 2017. Gadolinium deposition in the brain: association with various GBCAs using a generalized additive model. Eur Radiol. 27:3353–3361.
   PubMed Web of Science ®Google Scholar
• Baranyai Z, Brücher E, Uggeri F, Maiocchi A, Tóth I, Andrási M, Gáspár A, Zékány L, Aime S. 2015. The role of equilibrium and kinetic properties in the dissociation of Gd[DTPA-bis(methylamide)] (Omniscan) at near to physiological conditions. Chem Eur J. 21:4789–4799.
   PubMed Web of Science ®Google Scholar
• Baranyai Z, Pálinkás Z, Uggeri F, Maiocchi A, Aime S, Brücher E. 2012. Dissociation kinetics of open-chain and macrocyclic gadolinium(III)-aminopolycarboxylate complexes related to magnetic resonance imaging: catalytic effect of endogenous ligands. Chem Eur J. 18:16426–16435.
   PubMed Web of Science ®Google Scholar
• Behzadi AH, Farooq Z, Zhao Y, Shih G, Prince MR. 2018. Dentate nucleus signal intensity decrease on T1-weighted MR images after switching from gadopentate dimeglumine to gadobutrol. Radiology. 287:171398.
   Web of Science ®Google Scholar
• Bjørnerud A, Vatnehol SAS, Larsson C, Due-Tønnessen P, Hol PK, Groote IR. 2017. Signal enhancement of the dentate nucleus at unenhanced MR imaging after very high cumulative doses of the macrocyclic gadolinium-based contrast agent gadobutrol: an observational study. Radiology. 285:170391.
   Web of Science ®Google Scholar
• Böhm I, Morelli J, Nairz K, Silva Hasembank Keller P, Heverhagen JT. 2017. Myths and misconceptions concerning contrast media-induced anaphylaxis: a narrative review. Postgrad Med. 129:259–266.
   PubMed Web of Science ®Google Scholar
• Bolles GM, Yazdani M, Stalcup ST, Creeden SG, Collins HR, Nietert PJ, Roberts DR. 2018. Development of high signal intensity within the globus pallidus and dentate nucleus following multiple administrations of gadobenate dimeglumine. Am J Neuroradiol. 39:415–420.
   PubMed Web of Science ®Google Scholar
• Bousquet JC, Saini S, Stark DD, Hahn PF, Nigam M, Wittenberg J, Ferrucci JT. 1988. Gd-DOTA: characterization of a new paramagnetic complex. Radiology. 166:693–698.
   PubMed Web of Science ®Google Scholar
• Boyken J, Frenzel T, Lohrke J, Jost G, Schütz G, Pietsch H. 2019. Impact of treatment with chelating agents depends on the stability of administered GBCAs: a comparative study in rats. Invest Radiol. 54:76–82.
   PubMed Web of Science ®Google Scholar
• Brasch RC, Weinmann HJ, Wesbey GE. 1984. Contrast-enhanced NMR imaging: animal studies using gadolinium DTPA complex. Am J Roentgenol. 142:625–630.
   PubMed Web of Science ®Google Scholar
• Burke LMB, Ramalho M, AlObaidy M, Chang E, Jay M, Semelka RC. 2016. Self-reported gadolinium toxicity: a survey of patients with chronic symptoms. Magn Reson Imaging. 34:1078–1080.
   PubMed Web of Science ®Google Scholar
• Cao Y, Huang DQ, Shih G, Prince MR. 2016. Signal change in the dentate nucleus on T1-weighted MR images after multiple administrations of gadopentetate dimeglumine versus gadobutrol. Am J Roentgenol. 206:414–419.
   PubMed Web of Science ®Google Scholar
• Cao Y, Zhang Y, Shih G, Zhang Y, Bohmart A, Hecht EM, Prince MR. 2016. Effect of renal function on gadolinium-related signal increases on unenhanced T1-weighted brain magnetic resonance imaging. Invest Radiol. 51:677–682.
   PubMed Web of Science ®Google Scholar
• Caravan P, Ellison JJ, McMurry TJ, Lauffer RB. 1999. Gadolinium(III) chelates as MRI contrast agents: structure, dynamics, and applications. Chem Rev. 99:2293–2352.
   PubMed Web of Science ®Google Scholar
• Clement O, Dewachter P, Mouton-Faivre C, Nevoret C, Guilloux L, Bloch Morot E, Katsahian S, Laroche D, Audebert M, Benabes-Jezraoui B, et al. 2018. Immediate hypersensitivity to contrast agents: the French 5-year CIRTACI study. EClin Med. 1:51–61.
   PubMedGoogle Scholar
• Conte G, Preda L, Cocorocchio E, Raimondi S, Giannitto C, Minotti M, De Piano F, Petralia G, Ferrucci PF, Bellomi M. 2017. Signal intensity change on unenhanced T1-weighted images in dentate nucleus and globus pallidus after multiple administrations of gadoxetate disodium: an intraindividual comparative study. Eur Radiol. 27:4372–4378.
   PubMed Web of Science ®Google Scholar
• Darrah TH, Prutsman-Pfeiffer JJ, Poreda RJ, Ellen Campbell M, Hauschka PV, Hannigan RE. 2009. Incorporation of excess gadolinium into human bone from medical contrast agents. Metallomics. 1:479–488.
   PubMed Web of Science ®Google Scholar
• Davenport MS. 2018. Choosing the safest gadolinium-based contrast medium for MR imaging: not so simple after all. Radiology. 286:483–485.
   PubMed Web of Science ®Google Scholar
• Dekkers IA, Roos R, van der Molen AJ. 2018. Gadolinium retention after administration of contrast agents based on linear chelators and the recommendations of the European Medicines Agency. Eur Radiol. 28:1579–1584.
   PubMed Web of Science ®Google Scholar
• Eisele P, Alonso A, Szabo K, Ebert A, Ong M, Schoenberg SO, Gass A. 2016. Lack of increased signal intensity in the dentate nucleus after repeated administration of a macrocyclic contrast agent in multiple sclerosis. Medicine. 95:e4624.
   PubMed Web of Science ®Google Scholar
• Eisele P, Szabo K, Ebert A, Radbruch A, Platten M, Schoenberg SO, Gass A. 2019. Diffusion-weighted imaging of the dentate nucleus after repeated application of gadolinium-based contrast agents in multiple sclerosis. Magn Reson Imaging. 58:1–5.
   PubMed Web of Science ®Google Scholar
• 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. Invest Radiol. 49:685–690.
   PubMed Web of Science ®Google Scholar
• Fingerhut S, Niehoff AC, Sperling M, Jeibmann A, Paulus W, Niederstadt T, Allkemper T, Heindel W, Holling M, Karst U. 2018. Spatially resolved quantification of gadolinium deposited in the brain of a patient treated with gadolinium-based contrast agents. J Trace Elem Med Biol. 45:125–130.
   PubMed Web of Science ®Google Scholar
• Flood TF, Stence NV, Maloney JA, Mirsky DM. 2017. Pediatric brain: repeated exposure to linear gadolinium-based contrast material is associated with increased signal intensity at unenhanced T1-weighted MR imaging. Radiology. 282:222–228.
   PubMed Web of Science ®Google Scholar
• Forslin Y, Shams S, Hashim F, Aspelin P, Bergendal G, Martola J, Fredrikson S, Kristoffersen-Wiberg M, Granberg T. 2017. Retention of gadolinium-based contrast agents in multiple sclerosis: Retrospective analysis of an 18-year longitudinal study. AJNR Am J Neuroradiol. 38:1311–1316.
   PubMed Web of Science ®Google Scholar
• Frenzel T, Apte C, Jost G, Schöckel L, Lohrke J, Pietsch H. 2017. Quantification and assessment of the chemical form of residual gadolinium in the brain after repeated administration of gadolinium-based contrast agents: comparative study in rats. Invest Radiol. 52:396–404.
   PubMed Web of Science ®Google Scholar
• Frenzel T, Lengsfeld P, Schirmer H, Hütter J, Weinmann HJ. 2008. Stability of gadolinium-based magnetic resonance imaging contrast agents in human serum at 37 °C. Invest Radiol. 43:817–828.
   PubMed Web of Science ®Google Scholar
• Fretellier N, Granottier A, Rasschaert M, Grindel A-L, Baudimont F, Robert P, Idée J-M, Corot C. 2019. Does age interfere with gadolinium toxicity and presence in brain and bone tissues? A comparative gadoterate versus gadodiamide study in juvenile and adult rats. Invest Radiol. 54:61–71.
   PubMed Web of Science ®Google Scholar
• Fretellier N, Idée JM, Dencausse A, Karroum O, Guerret S, Poveda N, Jestin G, Factor C, Raynal I, Zamia P, et al. 2011. Comparative in vivo dissociation of Gadolinium Chelates in renally impaired rats: a relaxometry study. Invest Radiol. 46:292–300.
   PubMed Web of Science ®Google Scholar
• Fretellier N, Idée JM, Bruneval P, Guerret S, Daubiné F, Jestin G, Factor C, Poveda N, Dencausse A, Massicot F, et al. 2012. Hyperphosphataemia sensitizes renally impaired rats to the profibrotic effects of gadodiamide. Br J Pharmacol. 165:1151–1162.
   PubMed Web of Science ®Google Scholar
• Gianolio E, Bardini P, Arena F, Stefania R, Di Gregorio E, Iani R, Aime S. 2017. Gadolinium retention in the rat brain: assessment of the amounts of insoluble gadolinium-containing species and intact gadolinium complexes after repeated administration of gadolinium-based contrast agents. Radiology. 285:839–849.
   PubMed Web of Science ®Google Scholar
• Gibby WA, Gibby KA, Gibby WA. 2004. 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. 39:138–142.
   PubMed Web of Science ®Google Scholar
• Grobner T. 2006. Erratum: Gadolinium - A specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant. 21:1745.
   Web of Science ®Google Scholar
• Grobner T, Prischl FC. 2008. Patient characteristics and risk factors for nephrogenic systemic fibrosis following gadolinium exposure. Semin Dial. 21:135–139.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Haylor J, Schroeder J, Wagner B, Nutter F, Jestin G, Idée J-M, Morcos S. 2012. Skin gadolinium following use of MR contrast agents in a rat model of nephrogenic systemic fibrosis. Radiology. 263:107–116.
   PubMed Web of Science ®Google Scholar
• Herazo-Bustos C, Tramontini J C, Mora S JA, Aluja J F, Navas C. 2017. Evaluation of signal intensity in dentate nucleus, pons, globus pallidus and thalamus in patients with multiple sclerosis: assessment of gadolinium retention. Rev Chil Radiol. 23:2–6.
   Google Scholar
• Hermann P, Kotek J, Kubícek V, Lukes I. 2008. Gadolinium(III) complexes as MRI contrast agents: ligand design and properties of the complexes. Dalton Trans. 23:3027–3047.
   PubMed Web of Science ®Google Scholar
• Heshmatzadeh Behzadi A, Zhao Y, Farooq Z, Prince MR. 2017. Immediate allergic reactions to gadolinium-based contrast agents: a systematic review and meta-analysis. Radiology. 286:162740.
   Web of Science ®Google Scholar
• Hinoda T, Fushimi Y, Okada T, Arakawa Y, Liu C, Yamamoto A, Okada T, Yoshida K, Miyamoto S, Togashi K. 2017. Quantitative assessment of gadolinium deposition in dentate nucleus using quantitative susceptibility mapping. J Magn Reson Imaging. 45:1352–1358.
   PubMed Web of Science ®Google Scholar
• Holesta M, Weichet J, Wagnerova M, Lukavsky J, Malikova H. 2018. Gadoxetate disodium, a modern hepatospecific MRI contrast agent: indirect signs for gadolinium deposition in the brain structures with signal intensity increase after intravenous application. Neurol India. 66:1771.
   PubMed Web of Science ®Google Scholar
• Hu HH, Pokorney A, Towbin RB, Miller JH. 2016. Increased signal intensities in the dentate nucleus and globus pallidus on unenhanced T1-weighted images: evidence in children undergoing multiple gadolinium MRI exams. Pediatr Radiol. 46:1590–1598.
   PubMed Web of Science ®Google Scholar
• Ichikawa S, Motosugi U, Omiya Y, Onishi H. 2017. Contrast agent-induced high signal intensity in dentate nucleus on unenhanced T1-weighted images comparison of gadodiamide and gadoxetic acid. Invest Radiol. 52:389–395.
   PubMed Web of Science ®Google Scholar
• Idée JM, Fretellier N, Robic C, Corot C. 2014. The role of gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: a critical update. Crit Rev Toxicol. 44:895–913.
   PubMed Web of Science ®Google Scholar
• Idée JM, Port M, Robic C, Medina C, Sabatou M, Corot C. 2009. Role of thermodynamic and kinetic parameters in gadolinium chelate stability. J Magn Reson Imaging. 30:1249–1258.
   PubMed Web of Science ®Google Scholar
• Idee J-M, Gaillard S, Corot C. 2012. Gadolinium-bound contrast agents: no evidence-based data to support a relationship between structure and hypersensitivity reactions. Indian J Dermatol. 57:245.
   PubMedGoogle Scholar
• Jaulent P, Hannoun S, Kocevar G, Rollot F, Durand-Dubief F, Vukusic S, Brisset JC, Sappey-Marinier D, Cotton F. 2018. Weekly enhanced T1-weighted MRI with Gadobutrol injections in MS patients: is there a signal intensity increase in the dentate nucleus and the globus pallidus? Eur J Radiol. 105:204–208.
   PubMed Web of Science ®Google Scholar
• Jost G, Frenzel T, Boyken J, Lohrke J, Nischwitz V, Pietsch H. 2019. Long-term excretion of gadolinium-based contrast agents: linear versus macrocyclic agents in an experimental rat model. Radiology. 290:340–348.
   PubMed Web of Science ®Google Scholar
• Jost G, Frenzel T, Lohrke J, Lenhard DC, Naganawa S, Pietsch H. 2017. Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue. Eur Radiol. 27:2877–2885.
   PubMed Web of Science ®Google Scholar
• Jost G, Lenhard DC, Sieber MA, Lohrke J, Frenzel T, Pietsch H. 2016. Signal increase on unenhanced T1-weighted images in the rat brain after repeated, extended doses of gadolinium-based contrast agents. Invest Radiol. 51:83–89.
   PubMed Web of Science ®Google Scholar
• Kahn J, Posch H, Steffen IG, Geisel D, Bauknecht C, Liebig T, Denecke T. 2017. Is there long-term signal intensity increase in the central nervous system on T1-weighted images after mr imaging with the hepatospecific contrast agent gadoxetic acid? A cross-sectional study in 91 patients. Radiology. 282:708–716.
   PubMed Web of Science ®Google Scholar
• Kanda T, Fukusato T, Matsuda M, Toyoda K, Oba H, Kotoku J, Haruyama T, Kitajima K, Furui S. 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Kanda T, Osawa M, Oba H, Toyoda K, Kotoku J, Haruyama T, Takeshita K, Furui S. 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.
   PubMed Web of Science ®Google Scholar
• Kang KM, Choi SH, Hwang M, Yun TJ, Kim J, Sohn C-H. 2018. T1 shortening in the globus pallidus after multiple administrations of gadobutrol: assessment with a multidynamic multiecho sequence. Radiology. 287:258–266.
   PubMed Web of Science ®Google Scholar
• Kang H, Hii M, Le M, Tam R, Riddehough A, Traboulsee A, Kolind S, Freedman MS, Li DKB. 2018. Gadolinium deposition in deep brain structures: relationship with dose and ionization of linear gadolinium-based contrast agents. AJNR Am J Neuroradiol. 39:1597–1603.
   PubMed Web of Science ®Google Scholar
• Kasper E, Schemuth HP, Horry S, Kinner S. 2018. Changes in signal intensity in the dentate nucleus at unenhanced T1-weighted magnetic resonance imaging depending on class of previously used gadolinium-based contrast agent. Pediatr Radiol. 48:686–693.
   PubMed Web of Science ®Google Scholar
• Khant ZA, Hirai T, Kadota Y, Masuda R, Yano T, Azuma M, Suzuki Y, Tashiro K. 2017. T1 shortening in the cerebral cortex after multiple administrations of gadolinium-based contrast agents. MRMS: Magn Reson Med Sci. 16:84–86.
   PubMed Web of Science ®Google Scholar
• Kinner S, Schubert TB, Bruce RJ, Rebsamen SL, Diamond CA, Reeder SB, Rowley HA. 2018. Deep brain nuclei T1 shortening after gadobenate dimeglumine in children: influence of radiation and chemotherapy. AJNR Am J Neuroradiol. 39:24–30.
   PubMed Web of Science ®Google Scholar
• Kiviniemi A, Gardberg M, Ek P, Frantzén J, Bobacka J, Minn H. 2019. Gadolinium retention in gliomas and adjacent normal brain tissue: association with tumor contrast enhancement and linear/macrocyclic agents. Neuroradiology. 1–10. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30710184
   PubMed Web of Science ®Google Scholar
• Kralik SF, Singhal KK, Frank MS, Ladd LM. 2018. Evaluation of gadolinium deposition in the brain after MR arthrography. AJR Am J Roentgenol. 211(5):1063–1067. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30106613
   PubMed Web of Science ®Google Scholar
• Kromrey M-L, Liedtke KR, Ittermann T, Langner S, Kirsch M, Weitschies W, Kühn J-P. 2017. 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
   PubMed Web of Science ®Google Scholar
• Langner S, Kromrey M-L, Kuehn J-P, Grothe M, Domin M. 2017. Repeated intravenous administration of gadobutrol does not lead to increased signal intensity on unenhanced T1-weighted images – a voxel-based whole brain analysis. Eur Radiol. 27:3687–3693.
   PubMed Web of Science ®Google Scholar
• Lee JY, Park JE, Kim HS, Kim S-O, Oh JY, Shim WH, Jung SC, Choi CG, Kim SJ. 2017. Up to 52 administrations of macrocyclic ionic MR contrast agent are not associated with intracranial gadolinium deposition: multifactorial analysis in 385 patients. PLoS One. 12:e0183916.
   Google Scholar
• Lohrke J, Frenzel T, Endrikat J, Alves FC, Grist TM, Law M, Lee JM, Leiner T, Li KC, Nikolaou K, et al. 2016. 25 Years of contrast-enhanced MRI: developments, current challenges and future perspectives. Adv Ther. 33:1–28.
   PubMed Web of Science ®Google Scholar
• Lord ML, Chettle DR, Gräfe JL, Noseworthy MD, McNeill FE. 2018. Observed deposition of gadolinium in bone using a new noninvasive in vivo biomedical device: results of a small pilot feasibility study. Radiology. 287:96–103
   PubMed Web of Science ®Google Scholar
• Malhotra A, LeSar B, Wu X, Durand D, Das N, Anzai Y, Sanelli P. 2018. Progressive T1 shortening of the dentate nucleus in patients with multiple sclerosis: result of multiple administrations of linear gadolinium contrast agents versus intrinsic disease. AJR Am J Roentgenol. 211(5):1099–1105. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30160975
   PubMed Web of Science ®Google Scholar
• Marie GPO, Pozeg P, Meuli RA, Maeder P, Forget J. 2018. Spatiotemporal pattern of gadodiamide-related T1 hyperintensity increase within the deep brain nuclei. Invest Radiol. 53(12):748–754. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30036232
   PubMed Web of Science ®Google Scholar
• Maximova N, Gregori M, Zennaro F, Sonzogni A, Simeone R, Zanon D. 2016. Hepatic gadolinium deposition and reversibility after contrast agent–enhanced MR imaging of pediatric hematopoietic stem cell transplant recipients. Radiology. 281:418–426.
   PubMed Web of Science ®Google Scholar
• McDonald RJ, McDonald JS, Kallmes DF, Jentoft ME, Murray DL, Thielen KR, Williamson EE, Eckel LJ. 2015. Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology. 275:772–782.
   PubMed Web of Science ®Google Scholar
• Miller JH, Hu HH, Pokorney A, Cornejo P, Towbin R. 2015. MRI brain signal intensity changes of a child during the course of 35 gadolinium contrast examinations. Pediatrics. 136:e1637–e1640.
   PubMed Web of Science ®Google Scholar
• Moreno J, Vaz NB, Soler JC, Carrasco JL, Podlipnick S. 2018. High signal intensity in the dentate nucleus on unenhanced T1-weighted MR images in melanoma patients receiving macrocyclic gadolinium-based contrast. J Radiol Diagnos Meth. 1:101.
   Google Scholar
• Moser FG, Watterson CT, Weiss S, Austin M, Mirocha J, Prasad R, Wang J. 2018. High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: comparison between gadobutrol and linear gadolinium-based contrast agents. AJNR Am J Neuroradiol. 39:421–426.
   PubMed Web of Science ®Google Scholar
• Müller A, Jurcoane A, Mädler B, Ditter P, Schild H, Hattingen E. 2017. Brain relaxometry after macrocyclic Gd-based contrast agent. Clin Neuroradiol. 27:459–468.
   PubMed Web of Science ®Google Scholar
• Murata N, Gonzalez-Cuyar LF, Murata K, Fligner C, Dills R, Hippe D, Maravilla KR. 2016. Macrocyclic and other non-group 1 gadolinium contrast agents deposit low levels of gadolinium in brain and bone tissue: preliminary results from 9 patients with normal renal function. Invest Radiol. 51:447–453.
   PubMed Web of Science ®Google Scholar
• Nehra AK, McDonald RJ, Bluhm AM, Gunderson TM, Murray DL, Jannetto PJ, Kallmes DF, Eckel LJ, McDonald JS. 2018. Accumulation of gadolinium in human cerebrospinal fluid after gadobutrol-enhanced MR imaging: a prospective observational cohort study. Radiology. 288:416–423.
   PubMed Web of Science ®Google Scholar
• Oksendal AN, Hals P-A. 1993. Biodistribution and toxicity of MR imaging contrast media. J Magn Reson Imaging. 3:157–165.
   PubMed Web of Science ®Google Scholar
• Öner AY, Barutcu B, Aykol Ş, Tali ET. 2017. Intrathecal contrast-enhanced magnetic resonance imaging–related brain signal changes. Invest Radiol. 52:195–197.
   PubMed Web of Science ®Google Scholar
• Ozturk K, Nas OF, Soylu E, Hakyemez B. 2018. Signal changes in the dentate nucleus and globus pallidus on unenhanced T1-weighted magnetic resonance images after intrathecal administration of macrocyclic gadolinium contrast agent. Invest Radiol. 53:535–540.
   PubMed Web of Science ®Google Scholar
• Palasz A, Czekaj P. 2000. Toxicological and cytophysiological aspects of lanthanides action. Acta Biochim Pol. 47:1107–1114.
   PubMed Web of Science ®Google Scholar
• Perrotta G, Metens T, Absil J, Lemort M, Manto M. 2017. Absence of clinical cerebellar syndrome after serial injections of more than 20 doses of gadoterate, a macrocyclic GBCA: a monocenter retrospective study. J Neurol.Neurol. 264:2277–2283.
   Web of Science ®Google Scholar
• Port M, Idée 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.
   PubMed Web of Science ®Google Scholar
• Quattrocchi CC, Mallio CA, Errante Y, Cirimele V, Carideo L, Ax A, Zobel BB. 2015. 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. 50:470–472.
   PubMed Web of Science ®Google Scholar
• Quattrocchi CC, van der Molen AJ. 2017. Gadolinium retention in the body and brain: is it time for an international joint research effort? Radiology. 282:12–16.
   PubMed Web of Science ®Google Scholar
• Radbruch A, Haase R, Kieslich PJ, Weberling LD, Kickingereder P, Wick W, Schlemmer H-P, Bendszus M. 2017. No signal intensity increase in the dentate nucleus on unenhanced T1-weighted MR images after more than 20 serial injections of macrocyclic gadolinium-based contrast agents. Radiology. 282:699–707.
   PubMed Web of Science ®Google Scholar
• Radbruch A, Weberling LD, Kieslich PJ, Eidel O, Burth S, Kickingereder P, Heiland S, Wick W, Schlemmer H-P, Bendszus M. 2015. Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent. Radiology. 275:783–791.
   PubMed Web of Science ®Google Scholar
• Radbruch A, Weberling LD, Kieslich PJ, Hepp J, Kickingereder P, Wick W, Schlemmer H-P, Bendszus M. 2015. High-signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted images. Invest Radiol. 50:805–810.
   PubMed Web of Science ®Google Scholar
• Radbruch A, Weberling LD, Kieslich PJ, Hepp J, Kickingereder P, Wick W, Schlemmer H-P, Bendszus M. 2016. Intraindividual analysis of signal intensity changes in the dentate nucleus after consecutive serial applications of linear and macrocyclic gadolinium-based contrast agents. Invest Radiol. 51:683–690.
   PubMed Web of Science ®Google Scholar
• Ramalho J, Castillo M, AlObaidy M, Nunes RH, Ramalho M, Dale BM, Semelka RC. 2015. high signal intensity in globus pallidus and dentate nucleus on unenhanced T1-weighted MR images: evaluation of two linear gadolinium-based contrast agents. Radiology. 276:836–844.
   PubMed Web of Science ®Google Scholar
• Ramalho M, Ramalho J. 2017. Gadolinium-based contrast agents: associated adverse reactions. Magn Reson Imaging Clin N Am. 25:755–764.
   PubMed Web of Science ®Google Scholar
• Ramalho J, Ramalho M, AlObaidy M, Nunes RH, Castillo M, Semelka RC. 2016. T1 signal-intensity increase in the dentate nucleus after multiple exposures to gadodiamide: intraindividual comparison between 2 commonly used sequences. Am J Neuroradiol. 37:1427–1431.
   PubMed Web of Science ®Google Scholar
• Ramalho J, Semelka RC, AlObaidy M, Ramalho M, Nunes RH, Castillo M. 2016. Signal intensity change on unenhanced T1-weighted images in dentate nucleus following gadobenate dimeglumine in patients with and without previous multiple administrations of gadodiamide. Eur Radiol. 26:4080–4088.
   PubMed Web of Science ®Google Scholar
• Ramalho J, Semelka RC, Ramalho M, Nunes RH, AlObaidy M, Castillo M. 2016. Gadolinium-based contrast agent accumulation and toxicity: an update. Am J Neuroradiol. 37:1192–1198.
   PubMed Web of Science ®Google Scholar
• Rasschaert M, Emerit A, Fretellier N, Factor C, Robert P, Idée JM, Corot C. 2018. Gadolinium retention, brain T1 hyperintensity, and endogenous metals: a comparative study of macrocyclic versus linear gadolinium chelates in renally sensitized rats. Invest Radiol. 53:328–337.
   PubMed Web of Science ®Google Scholar
• Rasschaert M, Schroeder JA, Wu T-D, Marco S, Emerit A, Siegmund H, Fischer C, Fretellier N, Idée J-M, Corot C, et al. 2018. Multimodal imaging study of gadolinium presence in rat cerebellum: differences between Gd chelates, presence in the virchow-robin space, association with lipofuscin, and hypotheses about distribution pathway. Invest Radiol. 53:518–528.
   PubMed Web of Science ®Google Scholar
• Renz DM, Kümpel S, Böttcher J, Pfeil A, Streitparth F, Waginger M, Reichenbach JR, Teichgräber UK, Mentzel HJ. 2018. Comparison of unenhanced T1-weighted signal intensities within the dentate nucleus and the globus pallidus after serial applications of gadopentetate dimeglumine versus gadobutrol in a pediatric population. Invest Radiol. 53:119–127.
   PubMed Web of Science ®Google Scholar
• Ringe KI, Husarik DB, Sirlin CB, Merkle EM. 2010. Gadoxetate disodium–enhanced MRI of the liver: part 1, protocol optimization and lesion appearance in the noncirrhotic liver. Am J Roentgenol. 195:13–28.
   PubMed Web of Science ®Google Scholar
• Robert P, Frenzel T, Factor C, Jost G, Rasschaert M, Schuetz G, Fretellier N, Boyken J, Idée J-M, Pietsch H. 2018. Methodological aspects for preclinical evaluation of gadolinium presence in brain tissue: critical appraisal and suggestions for harmonization - a joint initiative. Invest Radiol. 53:499–517.
   PubMed Web of Science ®Google Scholar
• Robert P, Lehericy S, Grand S, Violas X, Fretellier N, Ideé JM, Ballet S, Corot C. 2015. 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. 50:473–480.
   PubMed Web of Science ®Google Scholar
• Robert P, Violas X, Grand S, Lehericy S, Idée JM, Ballet S, Corot C. 2016. Linear gadolinium-based contrast agents are associated with brain gadolinium retention in healthy rats. Invest Radiol. 51:73–82.
   PubMed Web of Science ®Google Scholar
• Roberts DR, Chatterjee AR, Yazdani M, Marebwa B, Brown T, Collins H, Bolles G, Jenrette JM, Nietert PJ, Zhu X. 2016. Pediatric patients demonstrate progressive T1-weighted hyperintensity in the dentate nucleus following multiple doses of gadolinium-based contrast agent. AJNR Am J Neuroradiol. 37:2340–2347.
   PubMed Web of Science ®Google Scholar
• Roberts DR, Holden KR. 2016. 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. 38:331–336.
   PubMed Web of Science ®Google Scholar
• Robison RK, Pokorney A, Miller JH. 2018. Evaluation of the effect of switching from a linear to a macrocyclic contrast agent on the T1 -weighted brain signal intensity of a child during the course of 43 contrast-enhanced MRI examinations. J Magn Reson Imaging. 49(2):608–609. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30142238.
   PubMed Web of Science ®Google Scholar
• Rossi Espagnet MC, Bernardi B, Pasquini L, Figà-Talamanca L, Tomà P, Napolitano A. 2017. Signal intensity at unenhanced T1-weighted magnetic resonance in the globus pallidus and dentate nucleus after serial administrations of a macrocyclic gadolinium-based contrast agent in children. Pediatr Radiol. 47:1345–1352.
   PubMed Web of Science ®Google Scholar
• Runge VM. 2001. Allergic reactions to gadolinium chelates. Am J Roentgenol. 177:944–945.
   PubMed Web of Science ®Google Scholar
• Runge VM, Ai T, Hao D, Hu X. 2011. The developmental history of the gadolinium chelates as intravenous contrast media for magnetic resonance. Invest Radiol. 46:807–816.
   PubMed Web of Science ®Google Scholar
• Runge VM, Dickey KM, Williams NM, Peng X. 2002. Local tissue toxicity in response to extravascular extravasation of magnetic resonance contrast media. Invest Radiol. 37:393–398.
   PubMed Web of Science ®Google Scholar
• Runge VM, Stewart RG, Clanton JA, Jones MM, Lukehart CM, Partain CL, James AE. Jr. 1983. Work in progress: potential oral and intravenous paramagnetic NMR contrast agents. Radiology. 147:789–791.
   PubMed Web of Science ®Google Scholar
• Ryu YJ, Choi YH, Cheon JE, Lee WJ, Park S, Park JE, Kim WS, Kim IO. 2018. Pediatric brain: gadolinium deposition in dentate nucleus and globus pallidus on unenhanced T1-weighted images is dependent on the type of contrast agent. Invest Radiol. 53:246–255.
   PubMed Web of Science ®Google Scholar
• Schieda N, Blaichman JI, Costa AF, Glikstein R, Hurrell C, James M, Jabehdar Maralani P, Shabana W, Tang A, Tsampalieros A, et al. 2018. Gadolinium-based contrast agents in kidney disease: comprehensive review and clinical practice guideline issued by the Canadian association of radiologists. Can Assoc Radiol J. 69:136–150.
   PubMed Web of Science ®Google Scholar
• Schlemm L, Chien C, Bellmann-Strobl J, Dörr J, Wuerfel J, Brandt AU, Paul F, Scheel M. 2017. Gadopentetate but not gadobutrol accumulates in the dentate nucleus of multiple sclerosis patients. Mult Scler. 23:963–972.
   PubMed Web of Science ®Google Scholar
• Schneider GK, Stroeder J, Roditi G, Colosimo C, Armstrong P, Martucci M, Buecker A, Raczeck P. 2017. T1 signal measurements in pediatric brain: findings after multiple exposures to gadobenate dimeglumine for imaging of nonneurologic disease. AJNR Am J Neuroradiol. 38:1799–1806.
   PubMed Web of Science ®Google Scholar
• Semelka RC, Ramalho J, Vakharia A, AlObaidy M, Burke LM, Jay M, Ramalho M. 2016. Gadolinium deposition disease: initial description of a disease that has been around for a while. Magn Reson Imaging. 34:1383–1390.
   PubMed Web of Science ®Google Scholar
• Sieber MA, Lengsfeld P, Frenzel T, Golfier S, Schmitt-Willich H, Siegmund F, Walter J, Weinmann H-J, Pietsch H. 2008. 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. 18:2164–2173.
   PubMed Web of Science ®Google Scholar
• Splendiani A, Perri M, Marsecano C, Vellucci V, Michelini G, Barile A, Di Cesare E. 2018. Effects of serial macrocyclic-based contrast materials gadoterate meglumine and gadobutrol administrations on gadolinium-related dentate nuclei signal increases in unenhanced T1-weighted brain: a retrospective study in 158 multiple sclerosis (MS) patients. Radiol Med. 123:125–134.
   PubMed Web of Science ®Google Scholar
• Stojanov DA, Aracki-Trenkic A, Vojinovic S, Benedeto-Stojanov D, Ljubisavljevic S. 2016. 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 age. Eur Radiol. 26:807–815.
   PubMed Web of Science ®Google Scholar
• Tamrazi B, Liu C-S, Cen SY, Nelson MB, Dhall G, Nelson MD. 2018. Brain irradiation and gadobutrol administration in pediatric patients with brain tumors: effect on MRI brain signal intensity. Radiology. 289:188–194.
   PubMed Web of Science ®Google Scholar
• Tamrazi B, Nguyen B, Liu C-S, Azen CG, Nelson MB, Dhall G, Nelson MD. 2018. Changes in signal intensity of the dentate nucleus and globus pallidus in pediatric patients: impact of brain irradiation and presence of primary brain tumors independent of linear gadolinium-based contrast agent administration. Radiology. 287:452–460.
   PubMed Web of Science ®Google Scholar
• Tanaka M, Nakahara K, Kinoshita M. 2016. Increased signal intensity in the dentate nucleus of patients with multiple sclerosis in comparison with neuromyelitis optica spectrum disorder after multiple doses of gadolinium contrast. Eur Neurol. 75:195–198.
   PubMed Web of Science ®Google Scholar
• Taoka T, Jost G, Frenzel T, Naganawa S, Pietsch H. 2018. Impact of the glymphatic system on the kinetic and distribution of gadodiamide in the rat brain: observations by dynamic MRI and effect of circadian rhythm on tissue gadolinium concentrations. Invest Radiol. 53:529–534.
   PubMed Web of Science ®Google Scholar
• Taylor DM, Leggett RW. 2003. A generic biokinetic model for predicting the behaviour of the lanthanide elements in the human body. Radiat Prot Dosimetry. 105:193–198.
   PubMed Web of Science ®Google Scholar
• Tedeschi E, Palma G, Canna A, Cocozza S, Russo C, Borrelli P, Lanzillo R, Angelini V, Postiglione E, Morra VB, et al. 2016. In vivo dentate nucleus MRI relaxometry correlates with previous administration of Gadolinium-based contrast agents. Eur Radiol. 26:4577–4584.
   PubMed Web of Science ®Google Scholar
• Tibussek D, Rademacher C, Caspers J, Turowski B, Schaper J, Antoch G, Klee D. 2017. Gadolinium brain deposition after macrocyclic gadolinium administration: a pediatric case-control study. Radiology. 285:223–230.
   PubMed Web of Science ®Google Scholar
• Tweedle MF. 2007. “Stability” of gadolinium chelates. BJR. 80:583–584.
   Google Scholar
• Tweedle MF, Wedeking P, Kumar K. 1995. Biodistribution of radiolabeled, formulated gadopentetate, gadoteridol, gadoterate, and gadodiamide in mice and rats. Invest Radiol. 30:372–380.
   PubMed Web of Science ®Google Scholar
• Vergauwen E, Vanbinst A-M, Brussaard C, Janssens P, De Clerck D, Van Lint M, Houtman AC, Michel O, Keymolen K, Lefevere B, et al. 2018. Central nervous system gadolinium accumulation in patients undergoing periodical contrast MRI screening for hereditary tumor syndromes. Hered Cancer Clin Pract. 16:2.
   PubMed Web of Science ®Google Scholar
• Vidaud C, Bourgeois D, Meyer D. 2012. Bone as target organ for metals: the case of f-elements. Chem Res Toxicol. 25:1161–1175.
   PubMed Web of Science ®Google Scholar
• Wáng Y-X, Schroeder J, Siegmund H, Idée J-M, Fretellier N, Jestin-Mayer G, Factor C, Deng M, Kang W, Morcos SK. 2015. Total gadolinium tissue deposition and skin structural findings following the administration of structurally different gadolinium chelates in healthy and ovariectomized female rats. Quant Imaging Med Surg. 5:534–545.
   PubMed Web of Science ®Google Scholar
• Weberling LD, Kieslich PJ, Kickingereder P, Wick W, Bendszus M, Schlemmer HP, Radbruch A. 2015. Increased signal intensity in the dentate nucleus on unenhanced t1-weighted images after gadobenate dimeglumine administration. Invest Radiol. 50:743–748.
   PubMed Web of Science ®Google Scholar
• Weinmann HJ, Brasch RC, Press WR, Wesbey GE. 1984. Characteristics of gadolinium-DTPA complex: a potential NMR contrast agent. Am J Roentgenol. 142:619–624.
   PubMed Web of Science ®Google Scholar
• Welk B, McArthur E, Morrow SA, MacDonald P, Hayward J, Leung A, Lum A. 2016. Association between gadolinium contrast exposure and the risk of parkinsonism. JAMA. 316:96–98.
   PubMed Web of Science ®Google Scholar
• White GW, Gibby WA, Tweedle MF. 2006. 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. 41:272–278.
   PubMed Web of Science ®Google Scholar
• Yoo RE, Sohn CH, Kang KM, Yun TJ, Choi SH, Kim JH, Park SW. 2018. Evaluation of gadolinium retention after serial administrations of a macrocyclic gadolinium-based contrast agent (gadobutrol): a single-institution experience with 189 patients. Invest Radiol. 53:20–25.
   PubMed Web of Science ®Google Scholar
• Young JR, Orosz I, Franke MA, Kim HJ, Woodworth D, Ellingson BM, Salamon N, Pope WB. 2018. Gadolinium deposition in the paediatric brain: T1-weighted hyperintensity within the dentate nucleus following repeated gadolinium-based contrast agent administration. Clin Radiol. 73:290–295.
   PubMed Web of Science ®Google Scholar
• Young JR, Qiao J, Orosz I, Salamon N, Franke MA, Kim HJ, Pope WB. 2018. Gadolinium deposition within the paediatric brain: no increased intrinsic T1-weighted signal intensity within the dentate nucleus following the administration of a minimum of four doses of the macrocyclic agent gadobutrol. Eur Radiol. 28(11):4882–4889. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29744642
   PubMed Web of Science ®Google Scholar
• Zhang Y, Cao Y, Shih GL, Hecht EM, Prince MR. 2017. Extent of signal hyperintensity on unenhanced T1-weighted brain MR images after more than 35 administrations of linear gadolinium-based contrast agents. Radiology. 282:516–525.
   PubMed Web of Science ®Google Scholar
• Zhang Z, Nair SA, McMurry TJ. 2005. Gadolinium meets medicinal chemistry: MRI contrast agent development. CMC. 12:751–778.
   PubMed Web of Science ®Google Scholar