Contrast deposition: MRI agents

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  • Published: Jul 1, 2017
  • Author: David Bradley
  • Channels: MRI Spectroscopy
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Intracranial deposition

Robert J. McDonald, M.D., Ph.D. - New research published in the journal Radiology suggests that traces of the contrast agent gadolinium can be found in brain tissues many years after their use in magnetic resonance imaging (MRI). Intracranial deposition seems to occur even in patients with an intact blood-brain barrier.

New research published in the journal Radiology suggests that traces of the contrast agent gadolinium can be found in brain tissues many years after administration during magnetic resonance imaging (MRI). Intracranial deposition seems to occur even in patients with an intact blood-brain barrier.

Organometallic gadolinium chelates, often referred to as gadolinium based contrast agents (GBCAs), are used during MRI to carry the rare earth metal into the suspected disease site where it acts as a contrast agent by altering the relaxivity of local water molecules, and permitting detection of tissue pathologies that would otherwise be undetectable to unenhanced MRI or other imaging modalities. It was already known that small traces of gadolinium were retained in the brain tissue of patients years after undergoing an MRI brain scan. Furthermore, studies had hinted that such deposition was present only in patients with an underlying brain pathology, such as a tumour or infection. However, new research led by Robert McDonald MD PhD, a neuroradiologist and scientist at the Mayo Clinic in Rochester, Minnesota, USA, gadolinium retention may be more widespread and may be present in many more, or possibly all, patients in which GBCAs have been used. Whether this poses an ongoing risk to patient health remains to be seen.

GBCAs were first introduced into routine clinical practice in the late 1980s and are now an essential tool for many MRI scans around the world today. The contrast agent is injected intravenously and ultimately eliminated by excretion through the kidneys.

400 million doses

"It's estimated that approximately 400 million doses of gadolinium have been administered since 1988," says McDonald. "Gadolinium contrast material is used in 40 to 50 percent of MRI scans performed today."

It was assumed that the contrast material could not cross an intact blood-brain barrier. This protective semi-permeable membrane selectively filters materials from the bloodstream that might enter the extracellular fluid in the brain and the central nervous system.

"By late 2014, the first evidence emerged that gadolinium was depositing within brain tissues," McDonald adds. "However, many of these patients had underlying medical conditions, such as brain tumours, that could adversely affect the blood-brain barrier." "We were curious if this deposition might be related to the integrity of the blood-brain barrier, so we studied patients with normal brain pathology and presumably an intact blood-brain barrier."

The team carried out an analysis of post-mortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced MRI examinations between 2005 and 2015 and ten patients who had undergone MRI exams without a gadolinium contrast agent but were never exposed to a GBCA during their lifetime. The median age at the time of death was 68 years in the contrast agent-exposed group and 79 years in the control group. All of the GBCA exposed patients received gadodiamide (Omniscan).

Benefit over risk

Archived post-mortem brain tissue was obtained from each patient and studied with transmission electron microscopy, mass spectroscopy and X-ray spectroscopy, the team reports. The team found that there were dose-dependent gadolinium deposits in four neuroanatomical regions of the brain for patients who had undergone contrast-enhanced MRI. Their analysis showed, for instance, that the globus pallidus and dentate nucleus retained more of the gadolinium agent. Review of medical records and histopathological analysis found no pre-existing abnormalities or evidence of brain pathology.

"Our results suggest current thinking with regard to the permeability of the blood-brain barrier is greatly oversimplified, as gadolinium appears to accumulate even among patients with normal brain tissue and no history of intracranial pathology," says McDonald. "It will take additional research to understand how and why this deposition is occurring."

McDonald explains that, "These neuroanatomical regions of the brain are also areas prone to mineralization and haemorrhage, which may suggest that parts of the brain may have a less robust barrier and may be more susceptible to this deposition." Free gadolinium ions are similar in to calcium ions, particularly in size and charge. McDonald suggests that our bodies might therefore mistakenly identify gadolinium ions as calcium ions and allow it to be taken up in areas of the brain that would usually take up calcium. "These are all questions that need to be further explored," McDonald suggests.

It is important to note, that even though the team found evidence of GBCA accumulation in neural tissues, they did not see any histological changes that would suggest toxicity issues associated with these deposits. The regulatory bodies including the US Food and Drug Administration (FDA) and the National Institutes of Health (NIH) also state that there is no convincing scientific evidence to date that gadolinium might be problematic in this regard. Nevertheless continued investigations regarding the safety of these agents are needed.

"Gadolinium-based contrast agents have revolutionized MRI and diagnostic medicine," McDonald explains. "They have allowed us to detect diseases that would otherwise be extremely difficult to diagnose." Given that patients who present with the need for enhanced MRI may well have medical issues that if undetected would have unfavourable clinical outcomes, the risk-benefit equation for the use of GBCAs remains favourable. At the moment, the risk of not administering GBCAs is rare and the effects of GBCA tissue accumulation are at most only a theoretical risk. As this is an evolving field, we may find new evidence that will change our practice behaviour, but at the moment the evidence suggests these agents are safe, concludes McDonald.

Related Links

Radiol 2017, 161595: "Gadolinium Deposition in Human Brain Tissues after Contrast-enhanced MR Imaging in Adult Patients without Intracranial Abnormalities"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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