After the initial report in 2014 on T1-weighted (T1w) hyperintensity of deep brain nuclei following serial injections of linear gadolinium-based contrast agents (GBCAs), a multitude of studies on the potential of the marketed GBCAs to cause T1w hyperintensity in the brain have been published. The vast majority of these studies found a signal intensity (SI) increase for linear GBCAs in the brain—first and foremost in the dentate nucleus—while no SI increase was found for macrocyclic GBCAs. However, the scientific debate about this finding is kept alive by the fact that SI differences do not unequivocally represent the amount of gadolinium retained. Since the study design of the SI measurement in various brain structures is relatively simple, MRI studies investigating gadolinium-dependent T1w hyperintensity are currently conducted at multiple institutions worldwide. However, methodological mistakes may result in flawed conclusions. In this position statement, we assess the methodological basis of the published retrospective studies and define quality standards for future studies to give guidance to the scientific community and to help identify studies with potentially flawed methodology and misleading results.
• A multitude of studies has been published on the potential of the marketed GBCAs to cause T1w hyperintensity in the brain.
• The gadolinium-dependent T1w hyperintensity in the brain depends on patient’s history, types of GBCAs used (i.e., linear vs. macrocyclic GBCAs) and MR imaging setup and protocols.
• Quality standards for the design of future studies are needed to standardize methodology and avoid potentially misleading results from retrospective studies.
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American College of Radiology
European Medicine Agency
European Society of Urogenital Radiology
Food and Drug Administration
Gadolinium-based contrast agent
Gadolinium Retention Evaluation Consortium
Nephrogenic systemic fibrosis
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The GREC Task Force is an independent, voluntary body. No funding supported this work.
The scientific guarantor of this publication is Carlo C. Quattrocchi, Departmental Faculty of Medicine and Surgery, Head of the Unit of Diagnostic Imaging and Interventional Radiology, Università Campus Bio-Medico di Roma, Rome, Italy.
Conflict of interest
The authors of this manuscript declare relationships with the following companies:
C.C. Quattrocchi has received speaker honoraria from Bayer Healthcare; has organized the 1st and 2nd European GREC meetings in 2016 and 2017 sponsored by Bayer, Bracco, GE, and Guerbet.
J. Ramalho has organized the 2nd European GREC meeting sponsored by Bayer, Bracco, GE and Guerbet.
A. J. van der Molen has received chairman honoraria from Guerbet; has organized the 1st and 2nd European GREC meetings in 2016 and 2017 sponsored by Bayer, Bracco, GE, and Guerbet.
À. Rovira serves on scientific advisory boards for Novartis, Sanofi-Genzyme, Icometrix, SyntheticMR, and OLEA Medical, and has received speaker honoraria from Bayer Healthcare, Sanofi-Genzyme, Bracco, Merck-Serono, Teva Pharmaceutical Industries Ltd., Novartis, Roche, and Biogen Idec.
A. Radbruch: Bayer (invited talks, study funding, consultancy, advisory boards), Bracco (advisory board), Guerbet (invited talks, study funding, consultancy), GE (advisory board).
Statistics and biometry
No complex statistical methods were necessary for this paper.
Written informed consent was not required for this study because no original data were produced.
Institutional Review Board approval was not required because the paper is a recommendation statement and experiments were not performed.
International consensus statement on methodological recommendations on clinical studies
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Quattrocchi, C.C., Ramalho, J., van der Molen, A.J. et al. Standardized assessment of the signal intensity increase on unenhanced T1-weighted images in the brain: the European Gadolinium Retention Evaluation Consortium (GREC) Task Force position statement. Eur Radiol 29, 3959–3967 (2019). https://doi.org/10.1007/s00330-018-5803-6
- Contrast media
- Magnetic resonance imaging
- Dentate nucleus