Gadolinium Toxicity

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Gadolinium in the brain, is it harmful? Yes!

Editorial – Last December, I posted a Viewpoint titled “Gadolinium Retention – Is it all in my head?”  When I wrote that, I believed I had retained gadolinium in my brain, thyroid gland, and various other parts of my body.  I believed it, but I did not know it for sure.  It is one thing to think it, but it causes totally different feelings when you have confirmation that you have retained a toxic metal in your body.

On April 8, 2015, I posted about the gadolinium found in my thyroid tissue that was removed 51 months after my 5th dose of a linear gadolinium-based contrast agent.  In July, I learned that an analysis of my 2012 non-contrast brain MRI found evidence of gadolinium deposition in the globus pallidus; that MRI was performed exactly two years after my last dose of contrast.  Because of recently published studies, I was not surprised that they detected residual gadolinium in my brain.  At the time of my MRIs, except for hypertension and a past history of migraine headaches, I had no history of anything known to alter the blood-brain barrier.  Then and now, I continue to have “normal” renal function with an eGFR >60, but yet, I have evidence of long-term retention of gadolinium in my body.  If I only had gadolinium in my tissues and no symptoms, I might not worry about it as much, but that is not the case. (more…)

MultiHance found to leave residual gadolinium in the brain

A new study by Weberling et al, Increased Signal Intensity in the Dentate Nucleus on Unenhanced T1-Weighted Images after Gadobenate Dimeglumine Administration, found increased signal intensity (SI) in the dentate nucleus (DN) after serial injections of the linear gadolinium-based contrast agent (GBCA) gadobenate dimeglumine (MultiHance, Bracco Diagnostics Inc.).  The study included 50 patients that had a minimum of 5 consecutive brain MRI scans with MultiHance.  All MRIs were performed between March 1, 2014 and December 31, 2014 in the German Cancer Research Center, Heidelberg, Germany.  45 of the patients had an estimated glomerular filtration rate (eGFR) greater than 60, and 5 had an eGFR between 45 and 60.

Like the 2015 study by Radbruch et al, the exclusion criteria included: history of brain hemorrhage, stroke, or brain ischemia; edema, tumor, or other lesions located in the cerebellum or pons; history of intracranial infection, such as meningitis or encephalitis; missing or unsatisfactory unenhanced T1-weighted MRI scans; and missing documentation of the contrast agent administered.

The study found an increased SI in the DN-to-CSF (cerebrospinal fluid) and DN-to-pons ratios on unenhanced T1-weighted images in patients that had at least 5 MRIs with the gadolinium-based contrast agent MultiHance.  The authors said, “Because the previous work by McDonald et al showed that SI correlates with gadolinium retention in the respective area, the SI increase found herein likely reflects the specific potential of gadobenate dimeglumine to release gadolinium”. (more…)

Study reports Increasing Signal Intensity within the Brains of Patients with Multiple Sclerosis after multiple injections of the macrocyclic GBCA Gadovist – All Patients had Normal Renal Function

On June 25, 2015, European Radiology published a new study online ahead of print that reports increasing signal intensity on brain MR images after repeated administrations of the macrocyclic agent, gadobutrol (Gadovist, Bayer Healthcare, Berlin, Germany). The study by Stojanov et al is titled, Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol. This is the first study to report a correlation between the cumulative dose of a macrocyclic, gadolinium-based contrast agent (GBCA), and gadolinium deposition within the dentate nucleus (DN) and globus pallidus (GP) in patients with relapsing-remitting multiple sclerosis (RRMS).  All patients had normal renal function at the beginning and end of the study.

Liver function was also normal at the beginning of the study; however, the authors noted that at the end of the study there was a significant increase (p=0.004) in GGT, gamma-glutamyl transpeptidase.  The other liver function parameters remained normal.

Since all patients had normal renal function at the beginning and end of the study, there was no correlation between renal function and signal intensity within either dentate nucleus or globus pallidus.  The authors noted that, “This suggests that gadolinium deposition within the brain may occur even in patients with normal renal function”. (more…)

New study of Gadolinium retention in brains of rats raises more questions than it answers

On June 22, 2015, an article in Investigative Radiology was published online ahead of print.  The study by Robert et al, T1-Weighted Hypersignal in the Deep Cerebellar Nuclei After Repeated Administrations of Gadolinium-Based Contrast Agents in Healthy Rats – Difference Between Linear and Macrocyclic Agents”, describes for the first time “an animal model reproducing closely the recent clinical observations of cerebellum T1 signal hypersignal”.  “It also introduces an animal model to investigate the mechanism of the brain retention observed after repeated administrations of some GBCA.”

After 20 intravenous injections of 0.6 mmol of gadolinium per kilogram (4 injections per week for 5 weeks) of gadodiamide (Omniscan) or gadoterate meglumine (Dotarem) to healthy rats, they found that repeated injections of gadodiamide are associated with “progressive and persistent T1 signal hyperintensity in the deep cerebellar nuclei (DCN), with Gd deposition in the cerebellum in contrast with the macrocyclic GBCA gadoterate meglumine for which no effect was observed”.  Although repeated doses of gadoterate meglumine (Dotarem) did not cause signal increases, detectable concentrations of gadolinium were found in the cerebellum, cerebral cortex, and subcortical brain of the rats that were injected with it.  (more…)

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