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2020/05/30 11:22:16

Gadolinium

Gadolinium is a chemical element that underlies the contrast agents used for MRI. It is a soft metal with a silver tint. Gadolinium dissolves well, but is very toxic.

Content

In the video below, MRI of brain vessels with contrast.

This study is significantly more informative, especially for studying blood circulation and detecting tumors. A thick network of vessels is visible, supplying blood to the brain and other organs of the head and neck. Each vessel is clearly visible due to the fact that a paramagnetic contrast agent is introduced into the bloodstream - a salt of rare-earth metal gadolinium. Gadolinium is difficult to obtain in its pure form, so one dose of contrast for 2019 cost from 5 to 10 thousand rubles.

2023: Instead of poisonous gadolinium. Fresenius unveils MRI contrast agent substitute

On August 8, 2023, Fresenius Kabi announced the release of Gadobutrol, a universal contrast agent substitute for Gadavist, which is used in magnetic resonance imaging (MRI) procedures. Read more here.

2020: Giant doses of gadolinium from MRI patients found in Tokyo rivers

At the end of May 2020, ScienceDirect published a study, the authors of which claim that the use of gadolinium for MRI studies became an indirect cause of pollution of Tokyo rivers with toxic forms of this substance.

Researchers at Tokyo Metropolitan University found an increased concentration of gadolinium in river water throughout Tokyo, especially in areas near water treatment plants. They claim that gadolinium is excreted in the urine from patients' bodies within 24 hours of MRI and enters directly into the environment, where it turns into its toxic form under the influence of ultraviolet light. The authors highlighted the need for new government policies and technologies to remove gadolinium as the number of MRI scanners grows.

According to the study, the use of gadolinium for MRI studies has become an indirect cause of pollution of Tokyo rivers with toxic forms of this substance.
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Gd-based contrast agents used in magnetic resonance imaging are difficult to remove with conventional wastewater treatment technology, and they enter rivers when discharged from treatment plants, the paper says. - Anthropogenic Gd varies significantly depending on the location of wastewater treatment plants, and measurements showed a significant 5.0-6.6-fold increase in abnormal Gd concentration compared to data obtained 22 years ago.
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A similar study in Germany found that gadolinium residues used in MR studies are present in tap water and soft drinks served to restaurant patrons. The authors of this report, however, argued that the element was found in small quantities and posed no threat. However, the findings in Tokyo are worrying, especially as the number of MRI systems to serve Japan's aging population is on the rise.[1]

2019: Beginning to use new contrast to detect early stage liver disease

At the end of October 2019, hospitals began using a new contrast material based on gadolinium, which allows the detection of sub-millimeter tumor lesions in MRI images and warning of early-stage liver cancer.

A team of researchers led by Dr. Jenny J. Yang at Georgia State University have presented a new contrast that they believe is safer and more effective than existing gadolinium-based contrast agents. According to studies, the new material allows you to visualize liver tumors ranging in size from 0.1 mm to 0.2 mm on MRI scans.

Hospitals have begun using a new gadolinium-based contrast material that allows for the detection of sub-millimeter tumor lesions in MRI images and warning of early-stage liver cancer

Among people aged 45 to 64, liver disease deaths rose 31% from 2010 to 2015. Although liver diseases develop slowly, their progression can lead to serious consequences. Although MRI has advantages over other imaging techniques in relation to the diagnosis of non-alcoholic steatohepatitis and liver fibrosis, detection of liver tumors in the earliest stages is still difficult.

To address this, Dr. Young founded the InLighta BioSciences Research Laboratory to commercialize the ProCA32-collagen-1 protein-based contrast agent. Research has shown that the new agent makes it easy to differentiate fibrous areas from healthy tissue. In addition, when using the new contrast, the researchers found no gadolinium deposits in the brain. It is also worth noting that the new contrast can be used in much lower doses than other gadolinium-based contrast agents, which reduces its toxic effect on the patient.

The new contrast is expected to overcome major clinical barriers in the early non-invasive diagnosis of chronic liver disease.[2]

2018

Gadolinium enters the brain through cerebrospinal fluid

In July 2018, the results of a study were published in the journal Radiology, indicating the accumulation of gadolinium in cerebrospinal fluid (CSF) even in patients with an intact blood-brain barrier and normal kidney function.

Researchers at the Mayo Clinic in Rochester, Minnesota, found gadolinium in the cerebrospinal fluid of adult patients and children after administering a gadolinium-based macrocyclic contrast drug. Lead investigator Avinash Nehra notes that data on gadolinium accumulation in the intact blood-brain barrier may significantly influence further tactics for these drugs.

Gadolinium accumulates in CSF even in patients with intact blood-brain barrier

A prospective study was conducted in 82 patients, 68 of whom received macrocyclic gadolinium contrast gadobutrol ("Gadavist," Bayer HealthCare), and 14 belonged to the control group. All patients underwent lumbar puncture between June 2016 and December 2016. In the majority of patients (94%) who received gadobutrol for MRI during the preceding month, renal function was considered normal, the blood-brain barrier was intact (barrier integrity was determined by protein level in CSF). Gadolinium was detected in CSF samples of all 68 patients in the gadobutrol group (0.2-1494 ng/mL), regardless of age and protein level in CSF. Gadolinium concentrations were higher in adult patients as well as in patients with damaged blood-brain barrier. Gadolinium was found in CSF even in patients with contrast administered 24 days ago.

The researchers concluded that intravenous administration of gadobutrol is associated with immediate and constant accumulation of gadolinium in the CSF. It is not yet known whether the accumulation of gadolinium in CSF leads to the deposition of neurons in the tissue and whether this has clinical consequences - additional studies need to be carried out to clarify these data.[3]

Association between primary brain damage and gadolinium accumulation revealed

In May 2018, researchers at Children's Hospital Los Angeles published an article in the journal Radiology, where they suggested that the main factor influencing the penetration of gadolinium contrast into the brain may not be its concentration, but structural changes caused by brain tumors, and radiotherapy conducted by such patients.

These findings could seriously affect the direction of future research dealing with the accumulation of gadolinium contrasts in brain tissues - for example, there is a possibility that the cause of this phenomenon is the destruction of the blood-brain barrier. Gadolinium deposition studies began in December 2013, when Dr. Kanda et al published data showing that patients treated with gadolinium contrast agents during MRI scans showed increased signal intensity in the dentate nucleus and pale ball - subcortical structures of the brain. When subsequent studies showed that macrocyclic contrast agents accumulated in brain tissues to a lesser extent than linear ones, clinicians began to switch to this class of agents en masse. However, Dr. Tamrazzi's research allows you to consider the problem from a new perspective.

The main factor influencing the penetration of gadolinium contrast into the brain may not be its concentration, but structural changes caused by brain tumors, and radiotherapy conducted in such patients

The lead researcher of the new project, a specialist in the Department of Pediatric Neuroradiology at Children's Hospital Los Angeles, Dr. Benita Tamrazi, noted that in some cases the signal intensity does not directly depend on the dose of the injected contrast agent. In addition, she and her colleagues noted that previous studies had not conducted a comparative subanalysis of the population of children receiving radiotherapy and the population of children not receiving such treatment. Dr. Tamrationa and her colleagues examined the results of MRI scans, which were conducted using linear gadolinium contrasts to children with cancer between 2000 and the first half of 2015 (since July 2015, the hospital switched to macrocyclic gadolinium contrasts). The study involved 144 children under the age of 18 who underwent at least four MRI brain scans using the contrast "Magnevist" (Bayer HealthCare).

It was found that the presence of a primary pathological process, especially primary brain tumors, plays a significant role in the accumulation of gadolinium. In addition, in radiotherapy patients, gadolinium penetration was significantly higher if they performed up to 10 MRI studies with gadolinium contrast; in 20 or more MRI studies, the results were the opposite.

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These results significantly change the direction of our work regarding gadolinium contrasts and their accumulation in brain tissues, explained Dr. Tamrazzi. - Initially, we believed that gadolinium penetrates the brain dose-dependent. Now it becomes clear that this is not the only mechanism of accumulation of gadolinium contrasts in tissues and, probably, not leading.
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Dr. Tamrazzi observed that this study does not answer many of the pressing questions - the scientific community still knows the mechanism of accumulation of gadolinium in brain tissues and its long-term effect on the body. However, the results of the study show that the accumulation of gadolinium depends not only on the dose of the administered drug or its nature, but also on other factors that require careful study.[4]

A section on gadolinium retention in the body is included in the instructions for use of contrasts

In Apr 2018, updated instructions for the use of linear and macrocyclic gadolinium-based contrast agents were published with a section on gadolinium retention in the body. The instructions were updated based on the recommendations of the Medical Imaging Drugs Committee dated Sep 2017.

The instructions include information on several conditions that may occur with gadolinium contrasts and include nephrogenic systemic fibrosis, acute renal involvement and gadolinium retention. At the same time, linear contrast agents "cause delay to a greater extent" than macrocyclic ones.

In Apr 2018, updated DFU for linear and macrocyclic gadolinium-based contrast agents with gadolinium retention section was published

The instructions also indicate that the delay of gadolinium among linear agents is different: when using Omniscan and Optimark, the delay is higher than when administering Eovist, Magnevist and Multihans. The delay is minimal with macrocyclic agents and comparable with Dotarem, Gadavist and Prokhans.

In addition, the instruction states that although the clinical impact of gadolinium retention is still unknown, caution should be exercised when using contrast agents based on it.

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"Although no clinical consequences of gadolinium contrast retention in the body have been identified in patients with normal renal function, some patients may be at increased risk," noted in the instructions. "These groups include patients who require multiple contrast studies, pregnant women, children, and patients with inflammatory diseases."
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Information was obtained for the following contrast agents:

  • Gadoterata meglumin (Dotarem, Guerbet)
  • Gadoxetate (Eovist, Bayer HealthCare)
  • Gadobutrol (Gadavist, Bayer)
  • Gadopentetate dimeglumin (Magnevist, Bayer)
  • Gadobenate dimeglumin (Multihans, Bracco Imaging)
  • Gadodiamide (Omniscan, GE Healthcare)
  • Gadoveretamide (Optimark, Guerbet)
  • Gadoteridol (Bracco[5]

Japan imposes restrictions on gadolinium contrasts

On March 16, 2018, it became known that Japan introduced new restrictions on the use of linear contrast agents based on gadolinium. This was announced in his editorial published online in the journal "Magnetic Resonance in Medical Sciences," Dr. Tomonori Kanda from the University of Kobe.

Previously, both macrocyclic and linear gadolinium contrasts were allowed in Japan. But despite being considered safe for a long time, recent studies have shown that gadolinium contrasts tend not to be eliminated completely from the body, with linear contrast agents lingering more than macrocyclic ones, including in the brain. It is not yet clear whether the delay of gadolinium in the body affects the state of health. However, in November 2017, Japanese instructions for gadolinium contrasts were revised to reflect new data.

In March 2018, Japan introduced new restrictions on the use of linear contrast agents based on gadolinium

First, physicians were advised to limit the use of gadolinium-based contrasts and apply them only in cases where information provided exclusively by contrast research is required. Second, macrocyclic gadolinium contrasts became the drug of choice; linear contrasts can only be used in special circumstances where macrocyclic agents are not recommended for safety reasons (history of adverse effects). An exception was made for one linear contrast - gadoxetic acid.

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Although the risk of undesirable effects caused by residual gadolinium in the brain has not been proven, according to the revised recommendations, the use of linear gadolinium was limited, Dr. Kanda explained. - These measures are aimed at limiting possible undesirable effects in the future.[6]
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With a stroke, gadolinium can enter the eyeball

In early February 2018, researchers at the US National Institutes of Health (NIH) announced that gadolinium - a contrast used in MRI scans - could enter the eyeballs of stroke patients. The mechanism of contrast penetration is still unclear, although the phenomenon itself may have clinical consequences, according to an article dated February 7, 2018 in the journal Neurology.

First, gadolinium is injected during an MRI scan when a stroke patient is admitted to the hospital, and then on repeated examinations after 2 and 24 hours. As for the clinical significance of this phenomenon, the researchers found that patients with gadolinium penetration into both eyeballs two hours after admission had a more extensive brain stroke.

Gadolinium may end up in the eyeball in stroke, study finds
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Probably, our main discovery is that we have identified a link between the process of gadolinium penetration into the eyeball and brain damage, "said study author Dr. Richard Leigh of the National Institute of Neurological Disorders and Strokes (NINDS).
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The study began when an interesting phenomenon was discovered. When a patient with suspected stroke is admitted to the hospital, an MRI examination of the brain, most often with a gadolinium-based contrast agent, is performed to confirm the diagnosis.

In stroke, the blood-brain barrier is disrupted, allowing gadolinia to enter the brain parenchyma or cerebrospinal fluid (CSF). Without gadolinium, CSF, as a rule, merges with a dark background on MRI. Gadolinium changes the MR properties of CSF and the fluid is contrasted with light. However, during imaging studies, doctors noticed that in some cases gadolinium contrasts not only CSF, but also the contents of the eyeball.

Lee and colleagues included 167 stroke patients in the study who underwent an MRI study with gadolinium contrast on admission. Among the subjects, 109 patients (65%) received tissue plasminogen activator IV (tPA) and 58 (35%) did not receive tPA. Previous studies have shown that tPA can affect the blood-brain barrier, therefore, among other things, the researchers also assessed the effect of this therapy method on the penetration of gadolinium into the eyeballs.

MRI shows gadolinium leakage to eyes after contrast agent is injected into stroke patient


The researchers noted gadolinium penetration in 127 patients (76%) in one or both vitreous eyes on at least one of the three MRI scans.

It is worth noting that 14 patients with gadolinium penetration in both eyeballs two hours after admission had a large stroke zone compared to patients without gadolinium penetration.

Regarding the effect of tPA, there was no statistically significant association between tPA administration and gadolinium penetration into the eyeballs.

Despite the findings, Lee stated that the study's findings raise more questions than they provide answers.

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With this imaging biomarker, we established a link between processes occurring in the eyeball and those occurring in the brain of a stroke patient, "Lee explained. - However, we do not have enough information to declare the direct connection of these two events. Therefore, we cannot yet propose any changes to the strategy for diagnosis or therapy of stroke based on this study.
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How exactly does gadolinium get from the brain to the eyeball? It's too early to judge it yet. One possible pathway is to disrupt the integrity of blood vessels. Another way is to connect the eyeball with cerebrospinal fluid through the optic nerve. Lee suggests that the penetration of gadolinium into the eyeball is a consequence of a violation of the oculohematological barrier by analogy with a violation of the blood-brain barrier, but the researchers have yet to find out.[7]

2017

Withdrawal from sale of two gadolinium contrast agents in the UK

On December 15, 2017, it became known that by February 1, 2018, two widely used gadolinium-based contrast agents used in MRI studies would be withdrawn from sale in the UK. In this case, the use of other contrast agents will be strictly limited to individual readings. These innovations were announced by the UK Office for the Control of Medicines and Medical Devices (MHRA).

The Office is going to revoke marketing authorizations for linear gadolinium agents gadodiamide (Omniscan, GE Healthcare) and gadopentinic acid for intravenous administration (Magnevist, Bayer HealthCare Pharmaceuticals). Clinical indications for the other two gadolinium agents MultiHance (Bracco) and Primovist (Bayer) will be limited to use in delayed-phase MRI contrast.

UK halts sales of two gadilonium contrast agents

The move essentially reflects the activities of the European Medicines Control Agency (EMA). In early 2017, the agency ruled that Omniscan and Magnevist, as well as a third agent, Optimark from Guerbet, should be withdrawn from sale in Europe. The EMA gave manufacturers a year to implement this solution on the ground, however the MHRA has a more aggressive policy (for example, Guerbet has already recalled Optimark from the UK).

The MHRA expects providers to switch to alternative contrast MRI agents by February 2018. The MHRA explained that since 2006, the use of linear gadolinium-based contrasts has significantly decreased due to cases of nephrogenic systemic fibrosis in some patients. The question of the safety of these drugs was raised again after recent news of a minor delay in gadolinium in the brain of patients after MRI. Macrocyclic contrast MRI agents are thought to have much less gadolinium retention potential and should replace linear contrasts.[8]

FDA issues directive on gadolinium contrast requirement

On December 19, 2017, the US Food and Drug Administration (FDA) issued a directive that manufacturers of gadolinium-based contrast agents should add a new warning to the drug's instructions. In particular, they must notify medical professionals of delayed elimination of gadolinium from the body after magnetic resonance imaging (MRI).

The Dec. 19 decree also requires manufacturers to evaluate the safety of contrast agents in additional clinical studies. Now, before MRI, patients will receive a leaflet with new information on contrast agents. Finally, the department advises specialists to take into account the data obtained when deciding on the appointment of a contrast study.

Manufacturers of gadolinium contrast agents obliged to warn of slow withdrawal from the body
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We recommend that healthcare professionals consider that a drug containing gadolinium may linger in the body. Of particular note are cases where a contrast study is prescribed to patients who may need a repeat procedure, for example, for chronic disease, the FDA directive says.
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In May 2017, the Office completed a 21-month review of the safety of contrasts containing gadolinium, concluding that "to date, no harmful consequences" of gadolinium retention in the brain have been identified, which means that there is no need to introduce new restrictions.

However, the FDA now requires contrast agents manufacturers to conduct more research to identify new potential side effects of these drugs. European regulators are taking a more rigorous approach - in early 2017, they recommended that manufacturers withdraw three contrast drugs containing gadolinium from trade within 12 months. However, the FDA decided to wait for these additional studies before taking more drastic measures.[9]

Actor Chuck Norris sues gadolinium producers for poisoning wife

In early November 2017, the famous Hollywood actor Chuck Norris and his wife Gena began a lawsuit against 11 companies responsible for the production and distribution of gadolinium-based contrast agents (GBCA) used in magnetic resonance imaging (MRI), stating that their products caused severe health problems Gina. Read more here.

Gadolinium deposition in brain after MRI may be underestimated

At the end of June 2017, the online publication Radiology published the results of a study according to which the negative impact of gadolinium on human health may be stronger than scientists assumed. Contrast agents based on the substance can not only cause abnormalities in the brain, but also develop tumors and infections, a new report says.

It has long been thought that the blood-brain barrier, which prevents most molecules from passing freely between the blood and brain  and prevents toxins and microbes from entering the brain, prevents gadolinium contrast agents (GBCAs) from entering extracellular tissue fluid and central nervous system cells. Gadolinium is deposited in people's bodies after contrast-enhanced MRI scans, a new study says.

Gadolinium-based contrast agents can not only cause abnormalities in the brain, but also the development of tumors and infections.
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It is important that for a long time there was a thought of increasing the vulnerability of the blood-brain barrier in concomitant intracranial pathology, such as tumors, says the author of the report, Robert McDonald, who works as a neuroradiologist at the Mayo Clinic in Rochester (Minnesota, USA). - We have confirmed that these gadolinium agents are deposited even in the absence of intracranial pathology that could increase the permeability of the blood-brain barrier.
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AuntMinnie.com notes that MacDonald and his colleagues were the first to demonstrate strong evidence of gadolinium deposition in neuroanatomical regions of the brain: the dentate nucleus, thalamus, varolium bridge and pale ball. A study in March 2015 performed autopsies on 13 deceased people who were injected with gadolinium contrast agents between 2000 and 2014. Then there was another study, covering 15 people who had contrast MRI scans.

There are several theories that explain why gadolinium collects in these areas of the brain. One hypothesis is related to gadolinium properties, as in calcium. Some areas of the brain that consume increased doses of calcium mistakenly impersonate gadolinium. In addition, gadolinium deposition zones are more prone to hemorrhage and have a less stable blood-brain barrier, McDonald said.

The Mayo Clinic specialists' report made two main conclusions. First: gadolinium may be delayed after each dose of GBCA in adults.

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The second conclusion is contrary to our understanding of why all this deposition occurs. The data suggest the fallacy of our previous model, in which it was assumed that these deposits pass through the blood-brain barrier. Our results suggest that gadolinium accumulation in tissues may occur through an indirect mechanism that bypasses and does not directly cross the blood-brain barrier, noted Robert McDonald.
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According to him, gadolinium deposits are difficult to investigate, since the volumes of this substance in tissues are extremely small, therefore they require expensive medical equipment.

Linear gadolinium contrast agents are known to tend to accumulate in neural tissue. For macrocyclic gadolinium, the opposite has been proven.

Scientist Dirk Kle from the University Hospital of Dusseldorf (Germany) released the results of a study that analyzed 8,000 MRI studies, among which 24 children were found in whom the procedure with the macrocyclic drug gadolinium was performed at least 9 times. On average, these children were subjected to 14 such studies. Comparison with the control group did not reveal a tendency to accumulate contrast medium in brain tissues even with frequent MRI scans.[10]

Deposition in the brain of children

In May 2017, researchers from the Mayo Clinic in Rochester (Minnesota, USA) published a report confirming the deposition of gadolinium in the brain tissues of children with normal kidney function after contrast magnetic resonance imaging procedures .

A study of similar cases analyzed the brain tissue of children who died between 2000 and 2015. During their lifetime, they had at least four MRI studies with gadodiamide (Omniscan, GE Healthcare). Their samples were compared to those of a control group of three pediatric patients who never performed MRI scans using gadolinium.

Gadolinium used in MRI is deposited in the brains of children

According to the results of the study, its authors found gadolinium in all four neuroanatomical regions of the brain: the dentate nucleus, thalamus, varolium bridge and pale ball. The highest concentration of the substance was detected in the dentate core and varolium bridge.

Previously, numerous studies have proven that gadolinium is deposited in adult brains even after administration of gadolinium-based contrast agents (GBCAs) a few years earlier. Finding a similar situation in children is of greater concern as their brains develop and they are more susceptible to the neurotoxic effects of exposure to heavy metals. Therefore, new research is needed, as well as "smarter use of gadolinium contrast agents in pediatric patients," scientists say.

According to the Mayo Clinic, about 3 million pediatric MRI scans are performed in the United States each year, and gadolinium contrast agents are used in 40% of procedures. Despite this prevalence of the substance, previous studies on the effects of single or repeated GBCA administration have focused on adults.

Portal AuntMinnie.com notes that the emphasis in such studies may change. Earlier in 2017, German scientists found that the use of macrocyclic GBCA for MRI scans does not increase the signal intensity in the dentate nucleus of the cerebellum in children. The results are also consistent with a previous study of adult patients.[11]

Pediatric radiology departments reject linear contrast agents on gadolinia

In March 2017, it became known that concerns about the deposition of gadolinium in brain tissues prompted many departments of pediatric radiology in the United States to abandon the use of linear contrast agents based on this chemical element in favor of macrocyclic substances. The survey results are published in the journal Pediatric Radiology.

If in 2011 about 81% of pediatric departments of X-ray centers used linear gadolinium contrast agents, then in 2017 about 80% of institutions switched to macrocyclic gadolinium.

73% of the surveyed pediatric radiology departments in the United States, who refused to use linear gadolinium contrast agents, did this out of concern about the deposition of gadolinium in brain tissues
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One of the surprising points of the study was how many pediatric hospitals switch to macrocyclic agents a year later or are going to do so, says Dr. Michael Rozenfeld, a pediatric neuroradiologist at Banner Cardon Children Hospital (Mesa, Arizona, USA). - My thought is: if you can use the most stable agent, why not do it? It is better to be too careful, and, of course, there will be no harm from using a more stable agent.
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73% of the surveyed pediatric radiology departments in the United States, who refused to use linear gadolinium contrast agents, did this out of concern about the deposition of gadolinium in brain tissues. 47% of respondents also associated this step with an improvement in the safety profile, 33% with an increase in stability, 20% with a fear of nephrogenic systemic fibrosis. Only 7% of respondents abandoned linear contrasts in order to save money.

None of the healthcare facilities surveyed use linear nonionic agents. The four centers reviewed still use dimeglumin gadopentetate-based contrast agents, and the five centers use dimeglumin gadobenate-based contrast agents.[12]

Europe saw danger in gadolinium-based contrast agents

In March 2017, the European regulator proposed to remove several gadolinium-based contrast agents (GBCAs) from the market due to concerns that the substance remains in the human body after magnetic resonance imaging (MRI). We are talking about the most common drugs in medical imaging.

The recommendation was issued by the Pharmacovigilance Risk Assessment Committee (PRAC), which belongs to the European Medicines Agency (EMA), which in the EU is the main body regulating the pharmaceutical market.

Administration of Contrast Agent

In March 2017, a meeting on gadolinium safety was held at the PRAC. The issue was raised by the European Commission in 2016.

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The PRAC study of gadolinium-based agents provides strong evidence that the substance accumulates in the brain. This was shown by direct measurements of gadolinium in brain tissues and areas of increased signal intensity in MRI images taken many months after the last administration of gadolinium-based contrast agent, the Committee said.
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In 2016, the results of a study by the French pharmaceutical company Guerbet were published in the journal Investigative Radiology. Scientists conducted a series of experiments on rats to better understand the effects of repeated GBCA injections on the brain.

For 5 weeks, rodents received 20 injections of gadodiamide (gadodiamide), which belongs to linear GBCAs. Another group of animals was administered a second type of GBCA, the macrocyclic agent gadoterate meglumine. The third group was administered inactive saline (placebo).

The increase in signal intensity was maintained even after scientists stopped introducing contrast to rodents. Subsequent examinations found a high concentration of gadolinium in the brain of these rats, especially in the cerebellar region. Thus, animal experiments revealed serious risks associated with the use of traditional contrast drugs with gadolinium.

By March 2017, about 30 million gadolinium contrast procedures are performed annually worldwide. PRAC proposes to remove four linear gadolinium-based contrast agents from circulation:

  • gadobenic acid (manufactured by Bracco under the MultiHance brand);
  • gadodiamide (GE Healthcare sells under the name Omniscan);
  • gadopenthetic acid (Bayer HealthCare Pharmaceuticals under the name Magnevist);
  • gadoversetamide (company - Guerbet, trademark - Optimark).

According to the PRAC, linear contrast agents have a structure that is more likely to release gadolinium that accumulates in body tissues. Macrocyclic agents are more stable and less prone to release gadolinium.

The regulator's report notes that although no clinical diseases and even symptoms associated with gadolinium deposition were reported, the Committee decided to take a "precautionary position" due to insufficient data and the emergence of previously information on the development of nephrogenic systemic fibrosis (NSF) after contrast MRI using gadolinium. Earlier, the Food and Drug Administration (FDA) required additional information to be included in the instructions for gadolinium contrast agents to reduce the risk of developing NSF.

The PRAC promises to repeal the recommendations to ban gadolinium contrast agents if manufacturers provide new evidence that the benefits of using such substances alter the risks, or that gadolinium is not deposited in tissues in dangerous quantities.[13]

2016

Start discussion on gadolinium harms

In early 2016, Europe began to actively discuss the negative impact of gadolinium when used in magnetic resonance imaging (MRI). It is assumed that this rare earth metal can accumulate in brain tissues and cause serious diseases.

In early February 2016, the German newspaper Die Welt published an article under the headline "When metal in MRI settles in the brain." In particular, the authors of the note associated the use of gadolinium with Alzheimer's disease, and also concluded that it is better to replace MRI of the heart vessels of patients with myocardial scintigraphy.

Europe is oboscopic to the harmful effects of MRI
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"There is no evidence for all this," said Alexander Radbruch, a specialist in radiation diagnostics at the Heidelberg University Hospital (Germany), during a speech at the European Radiological Congress (March 2-6, 2016). "Radiologists need to avoid the fear of gadolinium, which can lead to a decrease in the use of contrast agents based on it."
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This metal, used in magnetic resonance imaging procedures over the years, improves the image of internal organs in the images and helps to make an accurate diagnosis. The issue of harm to gadolinium for the human body has been raised more than once.

So, in June 2015, scientists from the University of Pittsburgh concluded that the use of some contrast agents used in MRI in American clinics leads to the accumulation of gadolinium in brain tissues and bone tissue even with normal renal excretory function.

The head of the X-ray department of the hospital at the University of Bern (Switzerland), Johannes Heverhagen, is concerned that there are few studies proving the harmlessness of gadolinium to the brain, and they have all been conducted in the same center for a very long time. The professor stated that every substance used in MRI can produce gadolinium sediment in the brain, so it is likely that they will be removed from the market, and then radiologists will face a real problem.[14]

See also

Notes