The end of gadolinium use in MS imaging

T
Merry Christmas everyone, and Happy holidays 😊


Whilst, writing today’s blog post I find myself fortunate to be able to look back and say MS has come leaps and bounds over the last ten years, and looking ahead we stand at the cusp of an increasing number of clinical trials targeting progressive MS. Scientists and doctors have worked hard to improve the sensitivity of our diagnostic tests and we now understand more about the biology and the multitude of interactions that occur to trigger it than ever before.

So why have I picked this of all topics today to blog about on this important day? Not because I want to have a bit of a moan, but rather to point out that as we march ahead, we need to drop those interventions that have outlived their sell by date and provide no additional useful clinical information for our practice, beyond that of sentimentality. Adding contrast to MRI head scans to look for lesion activity, is one such example, but an important one – as it is becoming increasingly apparent that gadolinium compounds may deposit in the brain after administration (click to review an earlier blog on this topic). 

This article due to be published in Neurology, Neuroimmunology & Neuroinflammation, and again raises our awareness of this problem:

Neurol Neuroimmunol Neuroinflamm. 2018 Oct 19;6(1):e515. doi: 10.1212/NXI.0000000000000515. eCollection 2019 Jan.

Gadolinium in human brain sections and colocalization with other elements.

El-Khatib AH, Radbruch H, Trog S, Neumann B, Paul F, Koch A1, Linscheid MW, Jakubowski N, Schellenberger E.

They compared two autopsy sections of the cerebellum area (where greater deposits of gadolinium have been noted in the dentate nucleus of the cerebellum) from two patients compared to an age-matched patient without gadolinium administration. The first was a woman, aged 65, who died of sepsis and endocarditis (infection of the heart valves) and who had MRI with macrocyclic contrast two times, the last of which was 2 weeks before death, and the second was a man, aged 63, who died of pneumonia and heart failure, who underwent MRI scans  with macrocyclic contrast 9 weeks, 22 weeks, and 25 weeks before death.

Gadolinium signal was detected in the first person’s tissue in the dentate nucleus and cerebellar cortex and co-localised with iron, copper, zinc and phosphorous (see figure below). The second person, who received gadolinium four weeks before the assessment showed lower gadolinium signal than the first person, suggesting that there is a time-dependent excretion of the compound from the brain. Quantification studies showed that the amount of gadolinium in the tissues was 36 and 2ng/gram of brain tissue in the two patients, respectively.  Although, this work doesn’t convincingly provide evidence that gadolinium from macrocyclic contrast agents also deposit in the brain and are not washed out over time, it does raise concerns that there may be some deposition taking place over a limited period. 

Figure: Representative images of the cerebellum of patient Gd1 who received Gadovist 2 weeks before death and the control patient

Patient
Gd1 (A) and control patient (B): (a) Light image of a paraffin-embedded
section through the cerebellum. (b–f) element distribution
maps of phosphorus (P), gadolinium (Gd), iron (Fe), zinc (Zn), and
copper (Cu). Although the P signal is less in the Gd1 image compared
with the control, the relative intensities show clearly different
concentrations of P among the section. In the control image, the signal
is higher because of superior instruments settings but shows a uniform
distribution of P with no “hotspot” as in Gd1.

No long-terms adverse effects have been reported that are directly attributable to gadolinium administration in brain imaging studies. However, since we are now repeating them on an yearly basis, we should re-consider our blanket scanning protocols to administer contrast with every scan. If you haven’t discussed this already in your teams, make it the first thing in your agenda when you return to work. 

A Merry Christmas and Happy holidays, my heartfelt compliment.

About the author

Neuro Doc Gnanapavan

5 comments

  • As I am on Tysabri and am JCV positive, I have an MRI every 4 months. My MS center has changed which Gd compound they are using, but I now only use contrast once a year. PML does not enhance and I have been stable with no change for 12 years. This is one of those topics that must be patient driven. Common practice is just too easily continued.

    It would be wonderful to know before death if in fact you were retaining the Gd.

    Merry Christmas.

    • Yes Debbie, this is a discussion which everyone should be having. This study is particularly compelling as this is looking at the newer macrocyclic gadolinium instead of the older linear compounds.

  • Note this publication, which actually describes that gadolinium accumulation in the brain of pwMS is associated with poorer cognitive outcomes in neuropsychological testing:

    Forslin Y, Shams S, Hashim F, Aspelin P, Bergendal G, Martola J, . . . Granberg T: Retention of Gadolinium-Based Contrast Agents in Multiple Sclerosis: Retrospective Analysis of an 18-Year Longitudinal Study. AJNR Am J Neuroradiol 2017, 38(7):1311-1316. https://doi.org/10.3174/ajnr.A5211

    Interestingly, the patients investigated had a relatively low number of MRIs (up to 10). However, most MRIs were done with linear gadolinium agents. The modern macrocyclic agents bind Gd more tightly; hence, less Gd dissociates from the water soluable carrier-agent and accumulates in the tissue. But less does not mean none.

    I think that patients should challenge their Neurologists when they say that a Gd MRI has to be done "because it's the standard procedure", and ask whether it is really necessary and why.

  • I wonder what the role of diffusion weighted MR is in diagnosing/monitoring MS? I am wondering this as Ive had two MRIs recently – first scan which led to diagnosis during an acute admission was done without contrast but identified some large lesions which showed high signal on DWI – in the acute phase of MS I am assuming this finding on DWI means they are active lesions i.e equivalent of what would be contrast-enhancing lesions in contrast MRIs?
    So could DWI not be used to effectively replace the use of contrast MRIs in MS?

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