• Article
  • December 11, 2019

A Closer Look at the Shift to MRI Technology and GBCAs

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While MRI technology has an overarching benefit in terms of superior tissue definition compared to CT, it also has a safety advantage in pediatric settings, where limiting patients' radiation exposure is an important concern. Daniel Podberesky, M.D., Radiologist-in-Chief at Nemours Children's Health System, oversees radiology operations throughout a multistate hospital system. "In the last 10 to 15 years, with all the attention that was given to radiation exposure—mostly from CT scans—we have seen a shift toward MRI and ultrasound," he says.

"We've seen physicians move their ordering pattern away from CT toward MRI." Podberesky says one example is the workup of appendicitis. Currently, many pediatric hospitals use MRI for diagnosis of the condition, but 10years ago, such usage was almost nonexistent. Podberesky attributes this shift to the effort to minimize ionizing radiation exposure.

In addition to improved patient safety, Donna Roberts, M.D., associate professor of radiology at the Medical University of South Carolina, says contrast enhanced MRI (CEMRI)allows radiologists to better diagnose some pathologies, from congenital diseases to tumors to traumatic injuries. And pediatric patients may lack the ability to thoroughly describe symptoms, so CE-MRI can supply information the clinician is unable to obtainfrom the patient.

In cases of infection, Roberts says CE-MRI is useful because of vague symptoms. Through the MRI scan, providers can look inside and see what's going on. Podberesky says CE-MRI can also help with specific subsets of pathology. The diagnosis and staging of tumors and the diagnosis of infections and inflammatory processes are the two key areas where contrast agents—gadolinium-based contrast agents in particular—remain important for diagnosis.

Selecting a contrast agent

Based on the chemical structure of their chelates, gadolinium-based contrast agents (GBCAs) are classified as linear ormacrocyclic and can be ionic or nonionic, all of which are characteristics that may have an influence on the stability of the GBCA. Although non-contrast-enhanced MRIs may be sufficient for use in some clinical conditions, when selecting an agent for patient use, Roberts says doctors and hospitals take several factors into account including safety, stability, and the degree of image enhancement a provider is going to obtain.

According to Podberesky, there is a push in pediatric radiology to decide on a case-by case-basis if a contrast agent is necessary. "We're thinking about each child and case in a specific, individualized fashion and whether gadolinium is necessary to help answer a specific clinical question." In some cases, he says it's not necessary. "But, sometimes, the answer is absolutely, for what we're looking for, this child needs to have contrast." For example, a follow-up scan of a low-grade brain tumor may not require contrast, even if the initial, baseline scan used a contrast agent.

The shift towards macrocyclic agents

Podberesky says linear agents were inwidespread use at the start of the decade.However, he has firsthand experience with the movement toward macrocyclic agents. Before coming to Nemours, he was part of the radiology team at Cincinnati Children's Hospital Medical Center where he performed the first clinical administration of DOTAREM® (gadoterate meglumine) injection on a child in the U.S. Podberesky remembers the child he gave it to was a young girl who had a history of a renal tumor. "She was due for a follow up exam to look for any recurrence," he says. "Everything went as expected, and after that our use of DOTAREM increased rapidly. We replaced our linear agents throughout the system."

"I was an early believer in what was coming out in the literature, namely that the macrocyclic agents were illustrating higher stability rates than linear agents." The importance of stability was highlighted since the discovery of Nephrogenic Systemic Fibrosis in 2006, although, even to this day, the exact mechanism of NSF is unknown.

What is known, however, is that the immense majority of NSF cases were observed after administration of linear GBCAs, while few or no cases were observed with macrocyclic GBCAs. This led to labeling modifications and risk minimization measures worldwide, such as limits on the usage of most linear GBCAs in patients with severe renal impairment and in young children. Since then a drastic reduction in the number of NSF cases has been observed.

Additional literature has begun to develop regarding other differences between linear and macrocyclic agents. In 2014 Kanda et al. discovered an increased signal intensity in non-contrasted MRIs correlating with an increased cumulative dose of GBCAs. Since 2014, several publications in international scientific journals have suggested gadolinium deposition and accumulation in specific regions of the brain (globus pallidus and dentate nucleus) of patients receiving multiple administrations of GBCAs. Notably, an increased correlation to these hyper-intensities are seen more with linear agents than with macrocyclic agents.

Podberesky says the literature has become even more robust since then. "It's no longer a question that gadolinium is depositing in multiple places in the body. The current literature is very convincing that the macrocyclic agents are depositing to much less extent."

While patients—or their parents—may have concerns about gadolinium usage, Podberesky says there are a host of clinical indications where gadolinium remains the standard of care. It is widely recognized that CE-MRI increases diagnostic accuracy and confidence, and thus can impact the medical and surgical management of patients.

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