Gadolinium Presence in the Brain and Body

Increased signal intensity (SI) in the dentate nucleus (DN) and globus pallidus (GP) brain areas on unenhanced T1-weighted (T1w) MR images have long been observed. Historically, these brain hyperintensities have been associated with multiple sclerosis (MS)1, with accompanying iron deposition2, manganese deposition3, brain irradiation4 and hepatic dysfunction5. The first association of repeated gadolinium-based contrast agent (GBCA) administrations and increased SI on non-contrast T1w images in the DN and GP brain areas was published by Kanda et al.6 This study stimulated intensive scientific investigations that aim to better understand the origin of this SI increase (Figure 1).

To date, no study has shown an association between the observed increased SI in the brain after repeated GBCA administrations and the occurrence of any clinical adverse events. Additionally, no causal relationship has been established between clinical signs and symptoms and the presence of small amounts of gadolinium (Gd) in the body in patients with normal renal function following use of a GBCA.

Bayer has an extensive non-clinical research program underway to further evaluate these clinical findings in more detail and is actively participating in the ongoing discussions with leading experts worldwide.


Figure 1. Summary of key findings of clinical imaging studies that try to associate various gadolinium based contrast agents with signal intensity increase in the brain based on Bayer's interpretation of these studies (click here for a more detailed summary of these clinical imaging studies)

Summary of current clinical observations

  • Hyperintensity in the DN and GP brain areas has been observed after 5 or more administrations of multi-purpose linear GBCAs with standard dose (0.1 mmol Gd/kg body weight (BW)) in patients with normal renal function.6-15
  • No robust proof for any visual and/or statistically significant measurable SI increase on T1w images of the brain has been observed after a high number (up to 50 or more) of administrations of macrocyclic GBCAs (Dotarem, Gadovist, ProHance).11, 12, 14, 16-27
  • Similar brain hyperintensities as observed in adults were observed in pediatric studies21, 28-33 after multiple standard doses (0.1 mmol Gd/kg BW) of multi-purpose linear GBCAs.
  • No SI increase was seen following up to 15–18 administrations of Primovist34, 35, a liver-specific linear GBCA with a dual elimination pathway administered at ¼ the dose of other linear GBCAs. However, one study has shown a SI increase following a significantly higher number of administrations (ranging from 11–37 injections) while no SI was seen in patients with less than 10 Primovist injections.36
  • Despite differences in SI increase, no histopathological changes to brain tissue and no clinical adverse effects have been confirmed to be associated with this SI increase.38
  • Traces of gadolinium can be found in bone and brain after administration of either linear or macrocyclic GBCAs, regardless of renal function. Explorative data on the presence of gadolinium in some brain areas as well as bone tissue are provided by some post-mortem (seven in total) studies37-43
  • Reports of persistent or elevated gadolinium levels in certain areas of the body (blood, hair, nails, skin, and urine) have been reported with all GBCAs in a small number of patients who experience persistent symptoms which they associate with gadolinium presence.44, 45 To date, no adverse health effects have been confirmed to be associated with these findings.37-39


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  21. Yoo RE, Sohn CH, Kang KM, Yun TJ, Choi SH, Kim JH and Park SW. Evaluation of Gadolinium Retention After Serial Administrations of a Macrocyclic Gadolinium-Based Contrast Agent (Gadobutrol): A Single-Institution Experience With 189 Patients. Investigative radiology. 2017.
  22. Muller A, Jurcoane A, Madler B, Ditter P, Schild H and Hattingen E. Brain relaxometry after macrocyclic Gd-based contrast agent. Clin Neuroradiol. 2017.
  23. Cao Y, Huang DQ, Shih G and Prince MR. Signal Change in the Dentate Nucleus on T1-Weighted MR Images After Multiple Administrations of Gadopentetate Dimeglumine Versus Gadobutrol. AJR American journal of roentgenology. 2016;206:414-9.
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  25. Lee JY, Park JE, Kim HS, Kim SO, Oh JY, Shim WH, Jung SC, Choi CG and Kim SJ. Up to 52 administrations of macrocyclic ionic MR contrast agent are not associated with intracranial gadolinium deposition: Multifactorial analysis in 385 patients. PLoS One. 2017;12:e0183916.
  26. Lim WH, Choi SH, Yoo RE, Kang KM, Yun TJ, Kim JH and Sohn CH. Does radiation therapy increase gadolinium accumulation in the brain?: Quantitative analysis of T1 shortening using R1 relaxometry in glioblastoma multiforme patients. PLoS One. 2018;13:e0192838.
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