On March 11, 2015, a retrospective study on 46 patients with a meningioma who had routinely undergone follow-up enhanced-MRI scans with gadodiamide was published online in Investigative Radiology.  The authors report a significant increase in T1 hyperintensity of the dentate nuclei of the cerebellum on unenhanced scans was observed between the first and last MRI in the group of patients with a history of at least 6 enhanced MRI.  All patients had normal renal function before intravenous administration of gadodiamide (Omniscan).

Two recent studies (Kanda and Errante), with different cohorts of patients, have shown the association between high T1 signal intensity of the dentate nucleus and history of a high number of contrast-enhanced MRI in patients with cancer and brain metastases, and in patients with Multiple Sclerosis (MS).  It was suggested that this phenomenon may be related to multiple enhanced MRI scans conducted after intravenous administration of gadodiamide.

This study sought to address the hypothesis that the T1 hyperintensity of the dentate nucleus after multiple enhanced MRI scans is somehow linked to the interaction between gadodiamide and concurrent systemic treatments in patients with either MS or brain metastases.

46 patients were included in the study, all of whom had normal renal function.  The patients were separated into three groups: group A with 1 enhanced MRI scan (10 patients), group B with 1 to 5 enhanced MRI (28), and group C with at least 6 enhanced MRI scans (8).

A significant increase of dentate nucleus to pons ratios was observed between the first and last MRI in group C, whereas no differences were observed in group B.

Quattrocchi and his colleagues found this analysis conducted on a cohort of consecutive patients with meningioma and with no systemic interval therapy confirms that T1 signal hyperintensity of the dentate nucleus may be seen on unenhanced T1 images of patients undergoing multiple MRI scans with intravenous administration of gadodiamide.

The findings should “stimulate further consideration about the biodistribution and the molecular stability of gadodiamide, especially with respect to dechelation of the nonionic linear gadolinium chelates”.  Interestingly, the authors said that “gadodiamide does not cross the intact blood-brain barrier; therefore, we do not expect accumulation of gadodiamide in normal brain tissue or in central nervous system lesions that have not caused rupture of the blood-brain barrier”.  That was obviously written before the recently published study by McDonald et al that suggests “that gadolinium from administered GBCA is able to cross an otherwise intact blood-brain barrier and that compromise of this barrier is not necessary for tissue deposition”.

The authors noted that the findings reported by Kanda et al and Errante et al “have opened a debate on the safety of MRI Gadolinium-based Contrast Agents”.  I suspect that the McDonald et al study will take the debate to a much higher level.  One can only hope that research efforts currently underway will be fast-tracked.

For more information about Gadolinium and Gadolinium-Based Contrast Agents see Background on Gadolinium and Background on GBCAs in the Background section of our website.

Sharon Williams

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Quattrocchi, C. C., Mallio, C. A., Errante, Y., Cirimele, V., Carideo L., Ax A., & Zobel, B. B. (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. Investigative Radiology, 2015, Mar 11; Epub ahead of print. doi:10.1097/RLI.0000000000000154.  Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/25756685

McDonald, R. J., McDonald, J. S., Kallmes, D. F., Jentoft, M. E., Murray, D. L., Thielen, K. R., Williamson, E. E., et al. (2015). Intracranial Gadolinium Deposition after Contrast-enhanced MR Imaging. Radiology, 150025. doi:10.1148/radiol.15150025.  Retrieved from http://dx.doi.org/10.1148/radiol.15150025

Errante, Y., Cirimele, V., Mallio, C. A., Di Lazzaro, V., Zobel, B. B., & Quattrocchi, C. C. (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. Investigative Radiology, 49(10), 685–690. doi:10.1097/RLI.0000000000000072.  Retrieved from http://journals.lww.com/investigativeradiology/Fulltext/2014/10000/Progressive_Increase_of_T1_Signal_Intensity_of_the.8.aspx

Kanda, T., Ishii, K., Kawaguchi, H., Kitajima, K., & Takenaka, D. (2013). 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, 131669. doi:10.1148/radiol.13131669.  Retrieved from http://pubs.rsna.org/doi/abs/10.1148/radiol.13131669