Wednesday, 26 July 2017

#GuestPost: More on the safety of MRI contrast agents

A recent post on the safety of Gadolinium based contrast agents used in MRI caused some concern, so I thought we should follow up with yet more expertise and analysis. I therefore asked Dr Tom Campion to summarise his thoughts on a recent guidance statement by the International Society for Magnetic Resonance in Medicine (ISMRM) on this important topic.

Tom Campion is a senior radiology registrar at Barts Health NHS Trust, where he is currently undergoing neuroradiology training. He has an MSc in Neuroimaging for Research, and a research interest in imaging in multiple sclerosis. He is the trainee representative for the British Society of Neuroradiologists and runs a blog at www.bsnrtrainees.com. Tom has recently published a well received paper on a new method to improve the diagnosis of MS (free for download here). He has no conflicts of interest.


"Gadolinium-based contrast agents (GBCAs) are safe medications widely used in medical imaging, but have come under scrutiny due to the finding over the last few years that residual gadolinium is left in specific areas of the brain following their usage. The ISMRM published a recent guidance statement summarizing the evidence available so far, so here’s what we know [1]:

- In multiple studies, gadolinium has been found deposited in the brain, by imaging and by autopsy, long after GBCA administration
- This deposition appears more pronounced when people have had repeated doses of GBCA.
- Of the two types of GBCA, ‘linear’ and ‘macrocyclic’ (for a detailed explanation of the difference, see [2]), deposition is significantly more pronounced with linear compared to macrocyclic agents but has been demonstrated in both.
- The mechanism for the deposition is not yet understood.
- This has not been shown to cause any harm in human or animal models.

So what do we, as doctors and patients, do with this information? It is important to realize that we don’t give GBCAs for every MRI scan – each case is evaluated on an individual basis taking into account the potential benefits and risks. The benefits of GBCAs, simply put, are that they give us better images of abnormalities in the brain; the reason for this is that they penetrate the barrier between the blood vessels and the brain if there is a problem with the barrier, which is what we see in many people with neurological disease. Our ability to detect these problems is reduced by not using GBCAs. In the setting of multiple sclerosis, this is particularly important to evaluate the activity of the disease at a given time, as well as to exclude other potential causes for symptoms. 

Clearly, the benefit/risk consideration is now slightly different due to the introduction of a theoretical risk from gadolinium deposition, and should continue to be assessed on an individual case basis. But the multiple studies performed thus far, including large-scale population studies [3], have not shown any functional deficit related to the areas affected by the gadolinium deposition (the dentate nucleus and globus pallidus, which are primarily involved in the initiation and control of movement), or indeed any evidence of harm that can be directly linked to the deposition. 

My interpretation of the current evidence as a radiologist, particularly the ISMRM guidance [1] and the FDA safety statement [4], is this:
1. In the vast majority of contexts in which we give GBCAs, the benefits will outweigh these theoretical risks. Important treatment decisions are made based on these MRI scans, and these decisions are significantly better informed by our use of GBCAs, and thus more likely to lead to better outcomes for people with neurological disease.
2. This doesn’t mean we should dismiss these potential risks. On the contrary, we should seek further evidence on long term outcomes, find out the mechanism of gadolinium deposition, and design and use newer agents to prevent it if proved to be harmful.
3. We should also always be looking for other ways to image safely – researchers are already investigating other imaging techniques which could be used in future to avoid contrast administration [5].

Of course these findings are anxiety-provoking for people undergoing MRI scans, and it is important not to offer false reassurance; however, we should also not allow people to come to more harm as a result of avoiding a test that may be of significant benefit.

For those interested in further information, I recommend reading the recent ISMRM guidance statement [1] and the US Food & Drug Administration Drug Safety Communication [5], both of which are available for free online."


References
1. Gulani et al. (2017) Gadolinium Deposition in the Brain: Summary of Evidence and Recommendations. Lancet Neurol 16:564-70. Available at: http://www.ismrm.org/ismrm-position-paper-on-gd-deposition/
2. Kanal et al. (2014) Gadolinium contrast agents for CNS imaging: current concepts and clinical evidence. AJNR 35:2215-26.
3. Welk et al. (2016) Association Between Gadolinium Contrast Exposure and the Risk of Parkinsonism. JAMA 316:96-9.
4. FDA Drug Safety Communication: FDA identifies no harmful effects to date with brain retention of gadolinium-based contrast agents for MRIs; review to continue. Available at: https://www.fda.gov/Drugs/DrugSafety/ucm559007.htm
5. Gupta et al. (2017) The Use of Noncontrast Quantitative MRI to Detect Gadolinium-Enhancing Multiple Sclerosis Brain Lesions: A Systematic Review and Meta-Analysis. AJNR 38:1317-22.

1 comment:

  1. Thank you for the guest post - very informative and balanced - of benefit to have this knowledge as I approach the first of my annual post Alemtuzumab MRI this November.

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