Ablagerung von gadoliniumhaltigen Kontrastmitteln im Gehirn nach mehrfacher Anwendung: Konsequenzen für den Einsatz der MRT bei Diagnosestellung und Verlaufsbeurteilung der Multiplen Sklerose?

Zusammenfassung

Neue Studienergebnisse weisen auf einen Zusammenhang zwischen wiederholten kontrastmittel-unterstützen MRT-Untersuchungen und Ablagerung gadoliniumhaltiger Kontrastmittel im zentralen Nervensystem hin. Ein wesentlicher Faktor hierbei stellt möglicherweise die zum Einsatz kommende Kontrastmittelsubstanzklasse (linear bzw. makrozyklisch) dar. Über die letzten Jahrzehnte hat sich die MRT als ein unverzichtbarer Bestandteil in der Diagnostik, aber auch in der Verlaufsbeurteilung unterschiedlicher Erkrankungen etabliert. Dies gilt im besonderen Maße für chronische Erkrankungen, wie die Multiple Sklerose. Wiederholte MRT-Untersuchungen spielen hier insbesondere durch die zunehmenden Therapieoptionen eine wesentliche Rolle im Verlauf der Erkrankung. Im vorliegenden Artikel werden die derzeit vorhandenen Studienergebnisse über die Ablagerung gadoliniumhaltiger Kontrastmittel zusammengefasst und im Hinblick auf mögliche Konsequenzen für den Einsatz der MRT im Rahmen der Diagnose und insbesondere der Verlaufsbeurteilung der Multiplen Sklerose diskutiert.

Abstract

Recent studies have pointed towards a relationship between repetitive contrast- enhanced magnetic resonance imaging (MRI) and accumulation of gadolinium-based contrast agents. This relationship seems to be dependent on the subclass of contrast agents (linear vs. cyclic) used. Over the past decades, MRI has become one of the most valuable tools in the diagnosis and follow-up of a wide spectrum of disease entities. This holds true especially for chronic diseases such as multiple sclerosis. Given current strategies to establish MRI in treatment decision pathways due to the availability of more potential treatment options, repetitive MRI is frequently performed during the disease course of MS. In this article, we review currently available studies focusing on the accumulation of gadolinium-based contrast agents. Furthermore, consequences that may arise in the context of MR imaging in MS patients are discussed.

Schlüsselwörter

Magnetresonanztomografie - gadoliniumhaltige Kontrastmittel - Gadoliniumablagerung - Multiple Sklerose

Keywords

magnetic resonance imaging - gadolinium accumulation - multiple sclerosis - gadolinium-based contrast agents

• Literatur

• 1 Kanal E, Tweedle MF. Residual or retained gadolinium: practical implications for radiologists and our patients. Radiology 2015; 275: 630-634
• 2 Grobner T. Gadolinium – a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis?. Nephrol Dial Transplant 2006; 21: 1104-1108
• 3 Errante Y, Cirimele V, Mallio CA et al. 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: 685-690
• 4 Kanda T, Ishii K, Kawaguchi H et al. 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: 834-841
• 5 Ginat DT, Meyers SP. Intracranial lesions with high signal intensity on T1-weighted MR images: differential diagnosis. Radiographic 2012; 32: 499-516
• 6 Kanda T, Fukusato T, Matsuda M 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: 228-232
• 7 McDonald RJ, McDonald JS, Kallmes DF et al. Intracranial gadolinium deposition after contrast-enhanced mr imaging. Radiology 2015; 275: 772-782
• 8 Radbruch A, Weberling LD, Kieslich PJ et al. Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent. Radiology 2015; 275: 783-791
• 9 Robert P, Lehericy Sp, Grand S 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: 473-480
• 10 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; 275: 803-809
• 11 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: 805-810
• 12 Idee JM, Port M, Dencausse A et al. Involvement of gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: an update. Radiol Clin North Am 2009; 47: 855-869 vii
• 13 Stojanov DA, Aracki-Trenkic A, Vojinovic 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 2016; 26: 807-815
• 14 Weberling LD, Kieslich PJ, Kickingereder P et al. Increased signal intensity in the dentate nucleus on unenhanced T1-weighted images after gadobenate dimeglumine administration. Invest Radiol 2015; 50: 743-748
• 15 Ramalho J, Castillo M, AlObaidy M 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: 836-844
• 16 Roccatagliata L, Vuolo L, Bonzano L et al. Multiple sclerosis: hyperintense dentate nucleus on unenhanced T1-weighted MR images is associated with the secondary progressive subtype. Radiology 2009; 251: 503-510
• 17 Absinta M, Rocca MA, Filippi M. Dentate nucleus T1 hyperintensity in multiple sclerosis. AJNR 2011; 32: E120-E121
• 18 Janardhan V, Suri S, Bakshi R. Multiple sclerosis: hyperintense lesions in the brain on nonenhanced T1-weighted MR images evidenced as areas of T1 shortening 1. Radiology 2007; 244: 823-831
• 19 Brass SD, Chen NK, Mulkern RV et al. Magnetic resonance imaging of iron deposition in neurological disorders. Top Magn Reson Imaging 2006; 17: 31-40
• 20 Drayer B, Burger P, Hurwitz B et al. Reduced signal intensity on MR images of thalamus and putamen in multiple sclerosis: increased iron content?. AJR 1987; 149: 357-363
• 21 Gutteridge JM. Iron and oxygen radicals in brain. Ann Neurol 1992; 32 (Suppl) S16-S21
• 22 LeVine SM. Iron deposits in multiple sclerosis and Alzheimer's disease brains. Brain Res 1997; 760: 298-303
• 23 Powell T, Sussman JG, Davies-Jones GA. MR imaging in acute multiple sclerosis: ringlike appearance in plaques suggesting the presence of paramagnetic free radicals. AJNR 1992; 13: 1544-1546
• 24 Shan DE, Pan HC, Ho DM et al. Presence of activated microglia in a high-signal lesion on T1-weighted MR images: a biopsy sample re-examined. AJNR 2007; 28: 602
• 25 Terada H, Barkovich AJ, Edwards MS et al. Evolution of high-intensity basal ganglia lesions on T1-weighted MR in neurofibromatosis type 1. AJNR 1996; 17: 755-760
• 26 Zhou F, Shiroishi M, Gong H et al. Multiple sclerosis: hyperintense lesions in the brain on T1-weighted MR images assessed by diffusion tensor imaging. Journal of magnetic resonance imaging: JMRI 2010; 31: 789-795
• 27 Polman CH, Reingold SC, Banwell B et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69: 292-302
• 28 Vigeveno RM, Wiebenga OT, Wattjes MP et al. Shifting imaging targets in multiple sclerosis: from inflammation to neurodegeneration. Journal of magnetic resonance imaging: JMRI 2012; 36: 1-19
• 29 Barkhof F, Hommes OR, Scheltens P et al. Quantitative MRI changes in gadolinium-DTPA enhancement after high-dose intravenous methylprednisolone in multiple sclerosis. Neurology 1991; 41: 1219-1222
• 30 Burnham JA, Wright RR, Dreisbach J et al. The effect of high-dose steroids on MRI gadolinium enhancement in acute demyelinating lesions. Neurology 1991; 41: 1349-1354
• 31 Filippi M, Rocca MA. MR imaging of multiple sclerosis. Radiology 2011; 259: 659-681
• 32 Kappos L, Moeri D, Radue EW et al. Predictive value of gadolinium-enhanced magnetic resonance imaging for relapse rate and changes in disability or impairment in multiple sclerosis: a meta-analysis. Gadolinium MRI Meta-analysis Group. Lancet 1999; 353: 964-969
• 33 Fox RJ, Cree BA, De Seze J et al. MS disease activity in RESTORE: a randomized 24-week natalizumab treatment interruption study. Neurology 2014; 82: 1491-1498
• 34 Cotton F, Weiner HL, Jolesz FA et al. MRI contrast uptake in new lesions in relapsing-remitting MS followed at weekly intervals. Neurology 2003; 60: 640-646
• 35 Guttmann CR, Rousset M, Roch JA et al. Multiple sclerosis lesion formation and early evolution revisited: A weekly high-resolution magnetic resonance imaging study. Mult Scler 2015; Online First DOI: 10.1177/1352458515600247.
• 36 Miller DH, Barkhof F, Nauta JJ. Gadolinium enhancement increases the sensitivity of MRI in detecting disease activity in multiple sclerosis. Brain 1993; 116: 1077-1094
• 37 Bonzano L, Roccatagliata L, Mancardi GL et al. Gadolinium-enhancing or active T2 magnetic resonance imaging lesions in multiple sclerosis clinical trials?. Mult Scler 2009; 15: 1043-1047
• 38 Filippi M, Rocca MA, Arnold DL et al. Use of imaging in multiple sclerosis. In: European Handbook of Neurological Management. Gilhus NE, Brainin MM. ed. Blackwell Publishing; 2011: 35-51
• 39 Freedman MS, Patry DG, GrandʼMaison F et al. Treatment optimization in multiple sclerosis. Can J Neurol Sci 2004; 31: 157-168
• 40 Freedman MS, Selchen D, Arnold DL et al. Treatment optimization in MS: Canadian MS Working Group updated recommendations. Can J Neurol Sci 2013; 40: 307-323
• 41 Stangel M, Penner IK, Kallmann BA et al. Multiple Sclerosis Decision Model (MSDM): Entwicklung eines Mehrfaktorenmodells zur Beurteilung des Therapie- und Krankheitsverlaufs bei schubförmiger Multipler Sklerose. Akt Neurol 2013; 40: 486-493
• 42 Rio J, Castillo J, Rovira A et al. Measures in the first year of therapy predict the response to interferon beta in MS. Mult Scler 2009; 15: 848-853
• 43 Dobson R, Rudick RA, Turner B et al. Assessing treatment response to interferon-beta: is there a role for MRI?. Neurology 2014; 82: 248-254
• 44 Grand'Maison F, Bhan V, Freedman MS et al. Utility of the Canadian Treatment Optimization Recommendations (TOR) in MS care. Can J Neurol Sci 2013; 40: 527-535
• 45 Rio J, Rovira A, Tintore M et al. Relationship between MRI lesion activity and response to IFN-beta in relapsing-remitting multiple sclerosis patients. Mult Scler 2008; 14: 479-484
• 46 Sormani MP, Rio J, Tintore M et al. Scoring treatment response in patients with relapsing multiple sclerosis. Mult Scler 2013; 19: 605-612
• 47 Simon JH, Li D, Traboulsee A et al. Standardized MR imaging protocol for multiple sclerosis: Consortium of MS Centers consensus guidelines. AJNR 2006; 27: 455-461
• 48 Wattjes MP, Barkhof F. Diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy using MRI. Curr Opin Neurol 2014; 27: 260-270
• 49 Malayeri AA, Brooks KM, Bryant H et al. National Institutes of Health Perspective on Reports of Gadolinium Deposition in the Brain. J Am Coll Radiol 2016; 13: 237-241