David S. Enterline

The authors of our study have an ongoing interest in the use of gadolinium-based contrast agents (GBCAs) for neuro MRI. In January 2018, the FDA granted labeling for the use of gadobenate dimeglumine (MultiHance) in patients younger than 2 years of age, based on safety and diagnostic efficacy data collected in neonates and infants. Our group assisted in data collection and analysis submitted for that process, and subsequently with the manuscript published in AJNR. Two of the authors oversaw data collection from their children’s hospitals in a retrospective review of sequential patients who underwent contrast-enhanced MRI. The other 3 authors were blinded, off-site neuroradiology readers who compared multiple criteria of the nonenhanced and contrast-enhanced images.

Since approval of the first GBCA over 30 years ago, there have been more than 400 million administrations of GBCAs worldwide and this class of medication is known to be very well tolerated. Nevertheless, comparatively few studies have looked at patients younger than 2 years and, until recently, this indication was off-label. In line with reports elsewhere, our safety and diagnostic efficacy trial revealed no adverse events attributable to gadobenate and no other safety issues of potential concern.

In terms of diagnostic efficacy, as expected, gadobenate was useful for making specific clinical diagnoses compared with noncontrast imaging. One feature of interest was that the data collection hospitals used varying weight-based gadobenate contrast dosing ranging from 0.07 mmol/kg to 0.12 mmol/kg (in the case of multiple exams), rather than the standard 0.1 mmol/kg dose. This permitted us to compare higher and lower dosing levels. We found no significant difference in diagnostic quality for dosing less than or greater than 0.08 mmol/kg. A consequence of this finding is that the FDA now permits variable and lower dosing for gadobenate compared with other GBCAs in neonates and infants. Radiologists are encouraged to review their dosing policies.

One matter that remains to be addressed is the potential long-term effects, if any, of gadolinium retention in brain (and body) tissues. This is concerning for all patients but particularly for neonates and infants, whose brain and cognitive functions are still developing. Although no clinical manifestations attributable to gadolinium retention have yet been demonstrated in any patient population of any age, it remains our responsibility as radiologists to be vigilant and protective of our patients. The possibility to reduce the dose of gadolinium administered without loss of diagnostic information when using gadobenate is thus a distinct benefit for this population. Numerous studies in adults have demonstrated equivalent diagnostic performance for a lower dose of gadobenate compared with a standard dose of comparator agent, or superior diagnostic performance for a standard dose of gadobenate relative to an equivalent dose of comparator agent. Although comparison with other GBCAs was beyond the scope of our study, further study in this area may be warranted.

There has been strong support for this paper. Our data were presented at the ASNR 2020 virtual meeting and will also be adapted for presentation at RSNA 2020 this fall. Gadolinium dose reduction is an increasingly relevant topic and we are continuing our research effort to look not only at gadobenate but also at other GBCAs for the neonate and infant age group.

Read this article at AJNR.org …