Gadolinium in the brain: Wherefore Art Thou and How Comest?

This is an important paper. (see below Rasshaert et al JMRI 2020) It is written by experts from Guerbet, who make Dotarem, so one has to take that into consideration. The Guerbet scientists are actually great scientists and have written many important works on GBCAs..

Look at the figures they show of brain tissue electron microscopic images and read where they say: Gd is in interstitium or in the basement membranes (of the endothelial cells of blood vessels. They do not show Gd actually in brain nerve cells. They mention that Gd may be picked up by glial cells- which are not brain cells, brain cells are called neurons- glial cells are supporting cells.

There is one reference they cite that talks about in one specimen Gd was detected in a nucleus of some cell in the brain.

I have also cut out this passage from the paper, which you will find by reading the article:

Lastly, infusion of the chelating agent Ca-DTPA 7 weeks after a single administration of a linear GBCA to rats was associated with significant excretion of Gd in the urine.47 In parallel, the amount of Gd in the brain parenchyma decreased. This is consistent with mobilization of Gd from tissues.

To put it in plain language:

DTPA removes Gd from the brain PERIOD

In removing Gd with chelation, the Gd in brain parenchyma is decreased PERIOD

My opinion, based on this paper, and everything else I have read, .... the vast majority of Gd in the brain is not in brain cells (or any cells) but in the interstitial space also called extracellular matrix (ECM). Cells that seem to pick it up the most avidly are supporting tissue cells like endothelial cells (basement membranes- but this still could be trapped in collagen they produce and not in the cells themselves) and glial cells (cells that support the brain cells - the brain cells are the neurons). My guess then is 99% of Gd retained in the brain is in the interstitial space, 0.99% in supporting tissues (mainly endothelial cells of blood vessels) and 0.01% in brain cells themselves. I suspect that one of the additional functions of these supportive cells is to do specifically that, to pick up toxins so the neurons are not exposed to them, and thus brain cells are protected from picking them up themselves.

Show me electron microscopic images of Gd directly in neurons in numbers exceeding the amount in interstitial tissue, then I will believe that direct neuron deposition is a major source of brain Gd retention, until then I have to go with the images and data that are present in the literature. This is part of what I describe as wisdom-sense.

The major flaw you will recognize in this paper is they make the point that no evidence of clinical effects of Gd deposition in the brain are known..... so they are clearly wrong about that - but it circles back to the fact that they make Dotarem. So it is important to know what to believe based on the intrinsic bias of authors. Everything else is solid science.

Look also in the table on the Kconstant thermodynamic (or some column header like that Magnevist (which is Gd-DTPA) has higher stability than most of the other agents. Dotarem and Multihance are higher, but after some months Multihance will have come apart in the body so the Gd is more accessible (that is why we get a lot out with DTPA chelation of Multihance Gd), Dotarem should remain fully intact (that is why we don't get that much out of Dotarem but still a little)..

A separate subject from Deposition of Gd in the brain... which is mainly in the interstitial tissu; is what about the brain-related symptoms. I think a lot of the symptoms may not be from the Gd that is in the brain, but from cytokines elicited from Tissue resident memory T cells located everywhere in the body, including the brain, but by sheer amount of Gd deposition (and therefore number of tissue resident memory T cells), the largest sources of these cytokines are from skin and bones... but this is my opinion at this point.

Richard Semelka, MD

A Critical Review - Rasschaert - 2020 - Journal of Magnetic Resonance Imaging - Wiley Online Library To: <rcs2022199@gmail.com>, Richard Semelka <richardsemelka@gmail.com> https://onlinelibrary.wiley.com/doi/full/10.1002/jmri.27124