International Group Publishes Research Roadmap on Gadolinium Retention
Findings from NIH/ACR/RSNA gadolinium workshop published in Radiology.
September 12, 2018
A special report in Radiology provides a research roadmap to explore concerns about the safety of gadolinium-based contrast agents (GBCAs) and gadolinium retention.
Earlier this year, a workshop was held at the National Institutes of Health (NIH) in Bethesda, MD, to discuss the current literature on gadolinium, identify knowledge gaps, prioritize future research initiatives and foster collaborative standardized studies. The workshop was co-sponsored by the NIH, RSNA and the American College of Radiology (ACR).
Attendees included researchers, GBCA manufacturers and representatives of the U.S. Food and Drug Administration (FDA), invited based upon their expertise in a diverse set of scientific and clinical disciplines relevant to the study of the chemistry, measurement, clinical manifestations or health-related effects of retained gadolinium in human tissues.
“It is our hope that this roadmap can serve to promote global, comprehensive collaborative research that effectively addresses the many important questions on the clinical significance of gadolinium retention in patients undergoing contrast-enhanced MRI examinations,” said Herbert Y. Kressel, MD, co-author of the report, professor of radiology at Harvard Medical School in Boston and former editor of Radiology.
Since initial approval in 1988, over 450 million intravenous GBCA doses have been administered worldwide. Although GBCAs are considered safe, some types have been associated with nephrogenic systemic fibrosis, which occurs mainly in patients with advanced kidney disease .
More recently, mounting evidence has demonstrated long-term retention of gadolinium in human tissues after GBCA exposure. However, there is currently no scientific evidence that the retained gadolinium causes harm. Moreover, there is no proven scientific association between a range of patient-reported symptoms and GBCA exposure.
Identifying Vulnerable Patients
The workshop identified the need to specifically study potentially vulnerable populations of patients who might be susceptible to release of gadolinium-based compounds from long-term reservoirs, in bone for example. Vulnerable patient populations include post-menopausal women, pregnant or lactating women, fetuses and young children with growing bones and ongoing organ development and patients with chronic diseases who undergo a large number of contrast-enhanced MRI examinations.
“The workshop was helpful in identifying the knowledge gaps that need to be addressed to understand the clinical significance of observed signal increases in the brains of patients receiving these agents, as well as those due to the retention of gadolinium in bone, skin and liver and other portions of the brain that do not demonstrate signal intensity increases on MRI,” Dr. Kressel said. “Understanding the biologic changes due to the retention in these areas is essential in determining the clinical significance, if any, of gadolinium retention.”
The roadmap highlights knowledge gaps in GBCA research, proposes methods to address these gaps, identifies the feasibility and limitations of each approach and assesses priority levels. Crucial to these efforts is the standardization and validation of gadolinium and GBCA tissue measurement methods and quality assurance procedures.
The authors also point out the need to study existing large population databases, such as the Mayo Clinic Study of Aging, with large numbers of patients who undergo contrast-enhanced MRI exams. According to Dr. Kressel, analysis of these types of databases may help identify specific areas of concern that could be addressed in prospective, controlled studies.