Aspects For Choosing an MR Contrast Agent

MR contrast use has shifted almost entirely from linear to macrocyclic agents. “The key point is that the macrocyclic’s ring makes the agents more stable,” said Jay Pahade from Yale. However, there is more to consider.

MR contrast has been celebrating its 30th anniversary in 2018 – the first agent Gd-DTPA was approved in 1988. “The market for these contrast agents is still big”, said Jay Pahade, Yale University, New Haven/CT, USA. About 38 million MRI exams are currently performed in the USA, more than 50 percent with contrast. 

The Checklist

In order to choose the appropriate agent, radiologists need to include various aspects:

1. Safety
2. Stability
3. Altered property of one agent versus another. “Relaxivity and only extracellular versus combined properties are to consider,” said Pahade.
4. Ease of use. This refers to dosing, administration in terms of viscosity, and timing of bolus to the center of k-space to optimize the signal.
5. Length of exam. This aspect is particularly important for hepatobiliary agents.
6. Availability and cost. “This is one of the main things we are factoring in when choosing contrast: how much our health system can buy it for – that drives a lot of our decisions,” commented Pahade.

The ideal agent should be cheap, reach diagnostic levels of enhancement, be rapidly excreted from the body with no presence of gadolinium in the brain and other tissues and it should not cause any adverse events. “This would be the ideal agent”, said Pahade. 

What about NSF?

The initial FDA warning on nephrogenic systemic fibrosis (NSF) came out in 2006 with a label alteration in 2007. The current guidelines – in Europe and the US – explicitly name patients with an eGFR <30 or acute kidney injury as the risk group. Pahade referred to a recent review for comprehensive information on the topic (Schieda 2018).

“It is important to recognize that most people don’t get NSF”, underlined Pahade. “We are talking about a very small number of patients”. 

Traditional NSF Stratification Approach

The traditional approach would have been to avoid MR contrast in patients with an eGFR<30. This includes patients on dialysis, with chronic renal disease and acute kidney injury. An eGFR between 30 and 40 was “a kind of grey zone”, as Pahade put it. “But we need to realize that eGFR is a fluctuation value, as serum creatinine fluctuates”, he added. An eGFR above 40 was considered okay for contrast use. 

How Should NSF be Approached Now?

With stricter dosing, higher use of macrocyclics and no GBCA in patients on dialysis or with and eGFR <30, NSF incidence is now “basically zero”, said Pahade. 

Classifications of GBCAs in Europe and the US and Canada have played a role in this. While the basic tactic is similar on both continents, the EMA (European Medicines Agency) has taken a slightly different approach than the American College of Radiology (ACR) and the FDA (Food and Drug Administration). 

The US approach buckets GBCAs into three groups*:

  • Group I is what Pahade called the “high-risk” group. It contains gadodiamide, gadopentetate dimeglumine and gadoversetamide.
  • Group II is considered as “very low risk” for NSF and includes the three approved macrocyclic agents (gadoteridol, gadoterate meglumine and gadobutrol), as well as one linear agent (gadobenate dimeglumine).
    The ACR states that assessing renal function with a questionnaire or lab tests is optional prior to IV contrast at standard doses.
  • Group III with the hepatospecific gadoxetate disodium is the “we don’t really know” group, said Pahade.

The EMA classification differs only regarding the medium risk group (US Group II):

  • Both linear non-ionic hepatospecific agent gadoxetate disodium and the linear ionic gadobenate dimeglumine are considered medium risk.
  • All other linear agents are considered high-risk (US Group I).
  • All macrocyclic agents are considered low-risk (US Group III).

Other Adverse Events

Adverse effects for MR agents are low: Rates for allergic-like reactions to gadolinium-based agents are between 0.06 to 2.4%. Anaphylactic like reactions are even scarcer (0.001-0.01%).
However, differences between classes do exist: Macrocyclic non-ionic agents are reported to lead to more adverse events (Behzadi 2017). “The non-ionic macrocyclic agents we thought were the safest regarding NSF, lead to the highest risk for allergic-like events”, said Pahade. 

Pahade also mentioned one paper showing a temporary shortness of breath in patients receiving gadoxetate disodium (Davenport 2013).

Exposure to GBCAs during pregnancy might result in higher still-birth rates and higher incidences of rheumatologic like conditions, according to one study (Ray 2016). “Our general policy is to not give Gd, if the patient is pregnant”, underlined Pahade. 

Discussion

GBCA administration in pregnancy was a main discussion topic.  “We avoid it in pregnancy,” explained Pahade. “In the few cases we did it, it was always a risk-benefit decision,” he added.

Pahade also commented on renal function testing. “With the newer guidelines we have stopped testing renal function”, he said: “Even in patients with acute kidney injury, we still give gadolinium-based agents, if we need it – because based on the current data, the risk of NSF is almost negligible.” 

* Editorial Comment: The FDA has not used the grouping terms “high-risk“, “medium risk”, “low risk” or “very low risk”.  

References

Behzadi AH et al. Immediate Allergic Reactions to Gadolinium-based Contrast Agents: A Systematic Review and Meta-Analysis. Radiology. 2018;286(2):471-82.

Davenport MS et al. Effect of Gadoxetate Disodium on Arterial Phase Respiratory Waveforms Using a Quantitative Fast Fourier Transformation-Based Analysis. AJR Am J Roentgenol. 2017;208(2):328-36.

Ray JG et al. Association Between MRI Exposure During Pregnancy and Fetal and Childhood Outcomes. JAMA 2016;316(9):952-61.

Schieda N et al. Gadolinium-Based Contrast Agents in Kidney Disease: A Comprehensive Review and Clinical Practice Guideline Issued by the Canadian Association of Radiologists. Can J Kidney Health Dis 2018;5:2054358118778573

Presentation Title: Use of Iodinated and Gadolinium-based Contrast Media 2018: Is Your Clinical Practice Up to Date? Choosing an MRI contrast agent: Differences among gadolinium-based MR contrast agents with updates on nephrogenic systemic fibrosis (NSF) and renal function s
Speaker: Jay Pahade - Yale University
Date: 2018-11-27
Session code: RC407-3