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Could Artificial Intelligence replace Gadolinium-based Contrast Agents?

A new U.S. patent awarded to Imaging Biometrics for its IB Zero G artificial intelligence (AI) software might do what the FDA and Radiology Community have been reluctant to do – restrict or eliminate the administration of gadolinium-based contrast agents (GBCAs) for MRIs.

As recently reported by AppliedRadiology and HealthImaging, the fully automated AI technology, called IB Zero G, accepts non-contrast medical images as inputs and produces a synthetic image series that mimics contrast-enhanced images of comparable diagnostic quality. The IB Zero G software is currently in the investigational stage, but according to the company, is compatible with all MRI scanner platforms.

AI could eliminate the risk of gadolinium retention.

The FDA has acknowledged that gadolinium can remain in the body for months and years after contrast administration in all patients who have MRIs with a GBCA. However, no one has acknowledged that long-term retention of this toxic metal causes harm in people with normal renal function, even though retained gadolinium has been found to cause a potentially fatal, systemic disease process known as Nephrogenic Systemic Fibrosis (NSF) in people with end-stage renal disease.

I believe the key to avoiding harm from gadolinium is to avoid retaining any amount of it.

If IB Zero G can provide high quality diagnostic images without the use of GBCAs, it could protect patients from the long-term effects of retained gadolinium.  As Imaging Biometrics CEO Michael Schmainda said, “IB Zero G has the potential to significantly disrupt routine clinical workflows on a global basis and help millions of patients receive higher quality and safer MR exams.”

Hopefully, it will not take long for the IB Zero G AI technology to move from the investigational stage into routine use for what would have been GBCA-enhanced MRIs.

Sharon Williams
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References –
AppliedRadiology.com. June 24, 2021. https://appliedradiology.com/articles/patent-awarded-to-imaging-biometrics-for-no-contrast-mri-exams

HealthImaging.com. June 25, 2021. https://www.healthimaging.com/topics/ai-emerging-technologies/gadolinium-contrast-ai-software-us-patent

Food & Drug Administration. (2017). FDA Drug Safety Communication, December 19, 2017. Retrieved from https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-gadolinium-based-contrast-agents-gbcas-are-retained-body

 

 

 

 

Gadolinium was Retained in the Spinal Cord & Peripheral Nerves of Rats

A recent study by Alkhunizi et al., Gadolinium Retention in the Central and Peripheral Nervous System: Implications for Pain, Cognition, and Neurogenesis, found that gadolinium was retained, not only in the cerebrum, but also in the spinal cord and peripheral nerves of rats exposed to multiple administrations of linear and macrocyclic agents. Healthy rats were injected daily for 20 days with the linear gadolinium-based contrast agent (GBCA) gadodiamide or the macrocyclic agent gadoterate meglumine. Gadolinium (Gd) retention in the cerebrum, spinal cord, and peripheral nerves occurred with both agents; however, significantly more was retained from the linear agent gadodiamide.

The study also assessed the functional implications of Gd retention on hippocampal neurogenesis and sensory and cognitive processing. In rats, gadodiamide, but not gadoterate meglumine, led to pain hypersensitivity. The authors said their results show that repeat administration of gadodiamide leads to heat and mechanical hyperalgesia in rats, suggesting that the linear GBCA might have triggered the sensitization of spinal cord nociceptive neurons. Neither agent was found to affect spatial working memory performance, hippocampal cellular proliferation, or hippocampal neurogenesis.

Interestingly, the authors commented that “retention of gadolinium in the spinal cord and peripheral nerves might contribute to sensory symptoms and burning pain in the torso and extremities described by some patients after GBCA administration.” They also said, “eventually, attention must be drawn to the long-term effects of such metal retention in the central and peripheral nervous system, especially in children and adults with medical conditions necessitating multiple MRI examinations, such as brain tumors, spinal cord abnormalities, or multiple sclerosis.”

My thoughts

I agree that attention must be drawn to the long-term effects of metal retention in the body, but not eventually, it needs to happen now.

I think this is an important study because the focus is not just on the gadolinium that was retained in brain tissue. While the brain is vital to our survival, it is important to investigate where else it is being retained and to consider what adverse effects that might have on the human body. In the study by Alkhunizi et al., the results show that Gd retained in the spinal cord and peripheral nervous system can adversely affect nociceptive neurons. According to Krames (2014), nociceptive pain is the most common type of pain and results from signaling of noxious or potentially harmful stimuli by nociceptors around the body. Could that explain many of the neuropathic symptoms that patients have described after their MRIs with a gadolinium-based contrast agent?

Sharon Williams
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Alkhunizi, S. M., Fakhoury, M., Abou-Kheir, W., & Lawand, N. (2020). Gadolinium Retention in the Central and Peripheral Nervous System: Implications for Pain, Cognition, and Neurogenesis. Radiology, 192645. https://doi.org/10.1148/radiol.2020192645

Krames, E. S. (2014). The Role of the Dorsal Root Ganglion in the Development of Neuropathic Pain. Pain Medicine, 15(10), 1669–1685. https://doi.org/10.1111/pme.12413

Article says that Gadolinium-Based Contrast Agents should be used with extreme caution

A recently released review article by Drs. Katarina Leyba and Brent Wagner, titled “Gadolinium-based contrast agents: why nephrologists need to be concerned”, doesn’t pull any punches when it comes to the use of gadolinium-based contrast agents (GBCAs) for contrast-enhanced MRIs.  The authors said that ‘nephrogenic’ systemic fibrosis is a misnomer since GBCAs are the known trigger for the disease; kidney impairment is a risk factor.  They note that “the experimental evidence demonstrates that gadolinium-based contrast agents are biologically active – that is, not inert”.   Drs. Leyba and Wagner said that “because GBCAs are biologically active in vitro and in vivo, and patients with normal renal function have reported adverse events that overlap those of ‘nephrogenic’ systemic fibrosis (i.e., rash, muscle/tendon ‘tightness, pain…), and because the other risk factors are undetermined”, medical professionals need to be “open to the possibility that ‘nephrogenic’ systemic fibrosis and these gadolinium-based contrast agent-induced symptoms are part of a continuum”. (more…)

New White Paper about Health Risks of MRI Contrast Agents

The National Center for Health Research (NCHR) recently published a new white paper on its website about gadolinium-based contrast agents (GBCAs).   The title of the paper is “The Health Risks of Gadolinium-Based Contrast Agents used in MRIs” and the authors are Stephanie Fox-Rawlings, PhD, and Diana Zuckerman, PhD.  The paper provides a detailed history of GBCAs from regulation, to gadolinium toxicity and its clinical effects, possible treatments, and environmental exposure.

While there is much that we know about gadolinium and GBCAs, the authors acknowledge that there are still uncertainties, but that “the research thus far suggests that some people with healthy kidney function have been harmed by gadolinium.  This conclusion is based on the clear evidence of its accumulation and studies correlating its presence with symptoms”.

The authors pose several major questions concerning GBCAs and potential long-term harm.  They also describe the difficulties involved with designing studies to answer those questions.  However, they make it clear that new studies with carefully selected populations and study designs are needed.

Hopefully NCHR’s white paper about GBCAs will generate more research and interest in the potentially serious health risks associated with gadolinium retention and its long-term toxic effects.

About NCHR –
NCHR is a nonprofit, nonpartisan think tank that is focused on research that can improve the health of adults and children.  They do not accept funding from companies that make medical treatments.

According to its website, NCHR focuses on the programs and policies that they believe can most benefit from the research-based information that they can provide and the attention that they can generate.

You can read the article and learn more about NCHR here –
http://www.center4research.org/health-risks-of-gbcas/

Sharon Williams

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