Magnetic resonance imaging (MRI) uses magnetic fields to provide detailed anatomic images that reflect distribution and magnetic properties of tissues (specifically of hydrogen nuclei in water and fat) to aid in diagnosis of many pathologic conditions. Gadolinium-based intravenous contrast agents (GBCA) provide additional information based on signal intensity changes after GBCA administration. GBCA are used in approximately 45% of MRI exams in the United States. In the 30 years since the first GBCA was introduced into clinical practice, almost a half billion enhanced MRI studies have been performed worldwide. In the field of gynecology, MRI is widely used to enhance detection of early breast cancers in women at elevated risk, or to better delineate complex pelvic anatomy in the setting of prior pelvic surgery, severe endometriosis, distorting fibroids, cervical, uterine cancer or ovarian cancer.
A recent concern with use of GBCA surfaced in 2014, when the link between permanent high T1 signal in the dentate nucleus and globus pallidus of the brain and repeated prior GBCA exposure was identified.1 Post-mortem analysis of these deep brain structures confirmed that gadolinium deposition in the brain of patients who had GBCA-enhanced MRI of any part of the body. Specifically, higher signal intensities were seen in patients who had undergone at least six contrast-enhanced MRI examinations compared to patients who had undergone only non-contrast MRI. Case reports in children noted the same pattern of gadolinium deposition as that seen in adult patients following GBCA.2 Industry-sponsored studies in rats serially exposed to GBCA found progressively higher signal intensity on imaging, which correlated with post-mortem gadolinium concentrations in the brain.3 Notably, at the time of this writing, no human or animal data have shown any association between GBCA exposure and neurologic toxicity or neurological symptoms related to gadolinium deposition in the dentate nucleus of globus pallidus.4 Ob/gyns need to be aware of the current data about gadolinium-based contrast and the potential implications of its use when they order MRI for their patients.
Consensus guidelines on GBCA
In response to the reports of gadolinium deposition in the brain of GBCA-exposed individuals, the US Food and Drug Administration (FDA) required a new class warning and other safety measures for all GBCA for MRI in December 2017. Updates to GBCA labeling in May 2018 stated that GBCA was safe and should be used when medically necessary, and directed MRI centers to make educational information available to every outpatient the first time they receive GBCA.5 The FDA Patient Medication Guide includes risk of gadolinium retention associated with the two types of GBCA (linear and macrocyclic) and indicates that linear GBCA appears to result in higher retention for longer periods of time than macrocyclic GBCA. Providers are encouraged to consider patient characteristics that may result in increased risk of gadolinium retention, and to minimize closely spaced or multiple GBCA MRI.
Gulani and colleagues, on behalf of the International Society for Magnetic Resonance in Medicine (ISMRM) summarized the evidence and offered guidelines to clinicians in Lancet Neurology.4,6 They highlighted incomplete understanding of the clinical implications and mechanisms that drive gadolinium deposition, and discordant data comparing different types of gadolinium. The authors advised health care professionals to use caution when administering GBCA and to carefully document when and why a specific GBCA is given to a patient. They did not endorse macrocyclic over linear GBCA, and suggested that patient and clinical factors in addition to pharmacokinetics of the available agents should guide selection of the best GBCA. The American College of Radiology independently endorsed the same recommendation.7 Finally, the ISMRM Summary urged ongoing research to elucidate clinical implications of gadolinium deposition. The Pharmacovigilance Risk Assessment Committee of the European Medicines Agency has proposed a ban on all linear agents. Radiologists from the National Institutes of Health have recommended that use of macrocyclic rather than linear agents be considered, if possible.8
The authors report no potential conflicts of interest with regard to this article.
- Kanda T, Osawa High signal intensity in dentate nucleus on unenhanced T1 weighted MRI images: association with linear versus macrocyclic gadolinium chelate administration. Radiology. 2015;275:803-809.
- Roberts DR, Holden KR. Progressive in of T1 signal intensity in the dentate and nucleus and globus pallidus on unenhanced T1-weighted MR images in the pediatric brain exposed to multiple doses of gadolinium contrast. Brain Devel. 2016;38:331-336.
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- Gulani V, Calamante FG, Shellock FG, et al. Gadolinium deposition in the brain: summary of evidence and recommendations Lancet Neurol. 2017;16:564-570.
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- European Medicines Agency. PRAC concludes assessment of gadolinium agents used in body scans and recommends regulatory actions, including suspension of for some marketing authorizations. March 2017 Available at http://www.ema.europa.eu/docs/en_GB/documnent_library/Press_release/2017/03.
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- BIRI Registry for Development and Validation of Novel MR Imaging Techniques, Cedars-Sinai Medical Center PI Dr Debaio Li (correspondence)
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