A new study by Weberling et al, Increased Signal Intensity in the Dentate Nucleus on Unenhanced T1-Weighted Images after Gadobenate Dimeglumine Administration, found increased signal intensity (SI) in the dentate nucleus (DN) after serial injections of the linear gadolinium-based contrast agent (GBCA) gadobenate dimeglumine (MultiHance, Bracco Diagnostics Inc.). The study included 50 patients that had a minimum of 5 consecutive brain MRI scans with MultiHance. All MRIs were performed between March 1, 2014 and December 31, 2014 in the German Cancer Research Center, Heidelberg, Germany. 45 of the patients had an estimated glomerular filtration rate (eGFR) greater than 60, and 5 had an eGFR between 45 and 60.
Like the 2015 study by Radbruch et al, the exclusion criteria included: history of brain hemorrhage, stroke, or brain ischemia; edema, tumor, or other lesions located in the cerebellum or pons; history of intracranial infection, such as meningitis or encephalitis; missing or unsatisfactory unenhanced T1-weighted MRI scans; and missing documentation of the contrast agent administered.
The study found an increased SI in the DN-to-CSF (cerebrospinal fluid) and DN-to-pons ratios on unenhanced T1-weighted images in patients that had at least 5 MRIs with the gadolinium-based contrast agent MultiHance. The authors said, “Because the previous work by McDonald et al showed that SI correlates with gadolinium retention in the respective area, the SI increase found herein likely reflects the specific potential of gadobenate dimeglumine to release gadolinium”.
This study adds to the growing body of evidence that indicates that linear GBCAs deposit gadolinium in the brain. A recently published study by Stojanov et al reported SI increase after serial administrations of the macrocyclic GBCA gadobutrol (Gadovist, Bayer Healthcare, Berlin, Germany). However, the current study notes, “preliminary data by our group tentatively challenge the results by Stojanov et al”.
Further research is needed to determine if all GBCAs leave gadolinium in the brain and other tissues of patients’ bodies. Previously published research has shown gadolinium deposition from a macrocyclic agent has occurred. Gibby et al (2004) found gadolinium in bone tissue removed from patients within days of receiving ProHance. Darrah et al (2009) found, “There is no significant difference in bone Gd concentration between patients exposed to Gd-DPTA-BMA (Omniscan) and Gd-HP-DO3A (ProHance)”. (See Background on Gadolinium).
The recent study by Robert et al with rats found detectable concentrations of gadolinium in the cerebellum, cerebral cortex, and subcortical brain of the rats that were injected with the macrocyclic GBCA Dotarem. In that study, Dotarem did not cause signal intensity increases, but gadolinium was found within the brains of the study animals.
What remains to be determined is how much retained gadolinium the human body can tolerate before irreparable harm is done.
Weberling, L. D., Kieslich, P. J., Kickingereder, P., Wick, W., Bendszus, M., Schlemmer, H.-P., & Radbruch, A. (9000). Increased Signal Intensity in the Dentate Nucleus on Unenhanced T1-Weighted Images After Gadobenate Dimeglumine Administration. Investigative Radiology, Publish Ah. Retrieved from http://journals.lww.com/investigativeradiology/Fulltext/publishahead/Increased_Signal_Intensity_in_the_Dentate_Nucleus.99273.aspx
Radbruch, A., Weberling, L. D., Kieslich, P. J., Eidel, O., Burth, S., Kickingereder, P., … Bendszus, M. (2015). Gadolinium Retention in the Dentate Nucleus and Globus Pallidus Is Dependent on the Class of Contrast Agent. Radiology, 150337. http://doi.org/10.1148/radiol.2015150337
McDonald, R. J., McDonald, J. S., Kallmes, D. F., Jentoft, M. E., Murray, D. L., Thielen, K. R., … Eckel, L. J. (2015). Intracranial Gadolinium Deposition after Contrast-enhanced MR Imaging. Radiology, 150025. http://doi.org/10.1148/radiol.15150025
Stojanov, D. A., Aracki-Trenkic, A., Vojinovic, S., Benedeto-Stojanov, D., & Ljubisavljevic, S. (2015). 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. European Radiology. http://doi.org/10.1007/s00330-015-3879-9
Gibby, W. A., Gibby, K. A., & Gibby, W. A. (2004). Comparison of Gd DTPA-BMA (Omniscan) versus Gd HP-DO3A (ProHance) retention in human bone tissue by inductively coupled plasma atomic emission spectroscopy. Investigative Radiology, 39(3), 138–42. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15076005
Darrah, T. H., Prutsman-Pfeiffer, J. J., Poreda, R. J., Ellen Campbell, M., Hauschka, P. V, & Hannigan, R. E. (2009). Incorporation of excess gadolinium into human bone from medical contrast agents. Metallomics : Integrated Biometal Science, 1(6), 479–88. Retrieved from http://pubs.rsc.org/en/content/articlehtml/2009/mt/b905145g