Q&A: Gadolinium update with leading MRI safety expert Emanuel Kanal, MD

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 - Kanal Headshot
Emanuel Kanal, MD
Source: University of Pittsburgh Medical Center

Numerous studies showing evidence of gadolinium retention in the brains of MRI contrast patients are building momentum for an industry-wide reassessment of the current usage of gadolinium-based contrast agents. A new editorial published in Radiology authored by Emanuel Kanal, MD, of the University of Pittsburgh Medical Center; and Michael Tweedle, PhD, of The Ohio State College of Medicine, advocates for increased accountability and oversight by radiologists regarding the administration of these agents. Kanal, a nationally recognized leader in the area of MRI safety, spoke with  Health Imaging for an exclusive interview regarding this new evidence of gadolinium retention and its potential impact on diagnostic imaging and patient safety.

HI: When did this issue of gadolinium retention in contrast MRI patients with normal kidney function first begin to come to light?

EK: We first heard from Kanda in 2014 (Radiology 2014;270:834–841) that there was T1-shortening in the brain. At that point we didn't know the cause of it: Is it gadolinium, or is it something else? If it is gadolinium, in what form? Is it gadolinium that has dissociated, which has its own adverse event potential, or is it gadolinium in its initial form just like you had injected it that somehow is accumulating in these tissues? When Kanda first published in 2014 we didn't know if it was the contrast agent Omniscan or Magnevist, or how much his patients had received of each one.

HI: And those patients began to show signs of gadolinium retention.

EK: Yes, and remember, as far as we knew, for patients with normal kidneys, you give the contrast, it does its thing, and then it gets excreted: There was either nothing left in the body after a while, or anything left in the body was of such trivial amount that it should be of no clinical consequence. Now we're hearing that, even in patients with normal kidneys, the magnetic behavior of these locations in the brain, as evidenced by non-enhanced MRI, is changing—it’s different from what it's supposed to be. So that's a surprise, but we don't know if there's any clinical consequence to that, we just know that it's not expected.

HI: Is there any indication that specific agents may be more prone to leaving behind residual contrast than others?

EK: Well in 2015, Kanda published another study showing that there was no such T1-shortening seen in patients who had received Prohance, a macrocyclic agent, but that we did see this T1- shortening in patients who had received Magnevist, a linear agent. So now, this is very much shades of Nephrogenic Systemic Fibrosis (NSF). Once again, we're seeing differentiation among the agents, in a way that seems to stratify in a manner similar to how they had differentiated along NSF concerns.

HI: So it could be possible that linear agents, and not necessarily macrocyclics, are causing all the problems?

EK: Well that may be one possibility, but we don’t yet have the science or knowledge to support such a generalization, and I am hesitant to try and automatically glibly apply it that way.

HI: What does all of this mean for the future of contrast-enhanced MRI?

EK: Well that's the interesting part: One of the co-authors of the recently published Mayo Clinic study has said something to the effect of ‘Well, no one has ever shown that this is harmful.’ That's true. But at the same time, no one has ever studied it to date, so how could they show whether it's harmful or not? Let's look at this the way a patient would: Gadolinium is a known toxin to humans. We would never put a heavy metal, a lanthanide, into a human. The only reasons we do is because number one, we chelate it, and thereby make it safer; number two, we expect to have substantial benefit to this patient by doing so; and number three, we expect that the body will get rid of it. Under those assumptions, it had been approved. Now, it is confirmed that a very small amount of this material is dissociating. It is also confirmed that a very small amount of it is remaining in the body for years and years and years after it was last injected.

HI: What do you think the response should be from the medical industry in light of these findings?

EK: Right now it seems as if we're being defensive. It's as if we're saying ‘don't take away my drugs, these are such very valuable, useful drugs.’ Of course they're valuable—they're exquisitely powerful, they have immensely aided our ability for diagnostic sensitivity and specificity. No one is going