Home » Posts tagged 'GBCAs' (Page 9)
Tag Archives: GBCAs
Gadolinium Bioeffects and Toxicity – Special Issue of MRI Journal
A special issue of the journal Magnetic Resonance Imaging has been published and it is dedicated to “Gadolinium Bioeffects and Toxicity”. The issue starts with a safety overview of GBCAs by MRI Safety expert Dr. Emanuel Kanal, and ends with articles by UNC Radiologist Dr. Richard Semelka. One of the articles provides the initial description of Gadolinium Deposition Disease (GDD) which, while recently named, has been around for a while.
The issue is broken down into 4 sections as shown below. The link will take you to the abstract, but you can access a PDF of the complete paper.
Introduction –
Kanal, E. (2016). Gadolinium based contrast agents (GBCA): Safety overview after 3 decades of clinical experience. Magnetic Resonance Imaging. http://doi.org/10.1016/j.mri.2016.08.017
MRI Findings –
Kanda, T., et al (2016). Gadolinium deposition in the brain. Magnetic Resonance Imaging, 34(10), 1346–1350. http://doi.org/10.1016/j.mri.2016.08.024
Radbruch, A. (2016). Are some agents less likely to deposit gadolinium in the brain? Magnetic Resonance Imaging, 34(10), 1351–1354. http://doi.org/10.1016/j.mri.2016.09.001
Ramalho, J., et al, (2016). Technical aspects of MRI signal change quantification after gadolinium-based contrast agents’ administration. Magnetic Resonance Imaging, 34(10), 1355–1358. http://doi.org/10.1016/j.mri.2016.09.004
Basic Sciences –
Murata, N., et al, (2016). Gadolinium tissue deposition in brain and bone. Magnetic Resonance Imaging, 34(10), 1359–1365. http://doi.org/10.1016/j.mri.2016.08.025
Prybylski, J. P., et al, 2016). Gadolinium deposition in the brain: Lessons learned from other metals known to cross the blood–brain barrier. Magnetic Resonance Imaging, 34(10), 1366–1372. http://doi.org/10.1016/j.mri.2016.08.018
Swaminathan, S., et al, (2016). Gadolinium toxicity: Iron and ferroportin as central targets. Magnetic Resonance Imaging, 34(10), 1373–1376. http://doi.org/10.1016/j.mri.2016.08.016
Tweedle, M. F., et al, (2016). Gadolinium deposition: Is it chelated or dissociated gadolinium? How can we tell? Magnetic Resonance Imaging, 34(10), 1377–1382. http://doi.org/10.1016/j.mri.2016.09.003
Future Directions –
Semelka, R. C., et al, (2016). Gadolinium deposition disease: Initial description of a disease that has been around for a while. Magnetic Resonance Imaging, 34(10), 1383–1390. http://doi.org/10.1016/j.mri.2016.07.016
Prybylski, J. P., et al, (2016). Can gadolinium be re-chelated in vivo? Considerations from decorporation therapy. Magnetic Resonance Imaging, 34(10), 1391–1393. http://doi.org/10.1016/j.mri.2016.08.001
Ramalho, J., et al, (2016). Gadolinium toxicity and treatment. Magnetic Resonance Imaging, 34(10), 1394–1398. http://doi.org/10.1016/j.mri.2016.09.005
Semelka, R. C., et al, (2016). Summary of special issue on gadolinium bioeffects and toxicity with a look to the future. Magnetic Resonance Imaging, 34(10), 1399–1401. http://doi.org/10.1016/j.mri.2016.09.002
My thoughts –
I believe this Special Issue is an important step in moving the discussion about gadolinium retention in patients with normal renal function forward. It seems that everyone now agrees that all patients exposed to gadolinium-based contrast agents retain some gadolinium from each dose of contrast that they receive. However, regardless of what you call it, patients are suffering from the toxic effects of retained gadolinium.
There is no doubt in my mind or the minds of other affected patients that retained gadolinium can cause chronic clinical symptoms of varying severity. Hopefully a large population of affected patients will be interviewed and examined soon. I believe that discussing symptoms with patients might trigger a thought process that leads researchers to uncover the missing pieces of the puzzle that explain the difference between what has been seen in brain tissue that contains gadolinium and the symptoms that patients are experiencing.
Sharon Williams
12/2/16
Study is first to report Gadolinium Toxicity in Patients with Normal Renal Function
“Presumed Gadolinium Toxicity in Subjects with Normal Renal Function – A Report of 4 Cases”, is a landmark paper which documents the first presumed cases of gadolinium toxicity. Richard C. Semelka, MD, Radiologist at the University of North Carolina at Chapel Hill, and his colleagues are the authors. This is the first study to describe a series of patients with normal renal function who developed symptomatology lasting beyond the immediate post-injection period after the administration of a gadolinium-based contrast agent (GBCA).
Two subjects were assessed at 2 months and at 3 months after GBCA administration (early stage), and 2 subjects were assessed at 7 years and 8 years after GBCA administration (late stage). Clinical features were similar between subjects, and included central torso pain (all), peripheral arm and leg pain (all), clouded mentation (2), and distal arm and leg skin thickening and rubbery subcutaneous tissue (one early and both late subjects). All subjects had evidence of gadolinium retention ranging from one month up to 8 years after disease development.
Regarding clinical findings, the authors note that “these 4 individuals showed features that resemble and are observed in NSF patients”. “Specifically, the glove-and-sock pattern of pain (seen in all patients) is essentially universally seen in NSF, and central torso pain (seen in 3 patients) is seen with some frequency, but not universally, in NSF patients. Skin thickening and doughiness of the hands was seen in the 2 subjects with late-stage disease and is also described as a feature that progressively develops with NSF.” They also noted that “headache and clouded mentation are vague and non-specific clinical symptoms; but they had new onset in 2 subjects”. While numerous recent studies report gadolinium deposition in the brain, no histopathological changes have been documented yet. They point out that a compound may be neurotoxic without being associated with histopathological signs.
These clinical features are comparable to the symptomatology reported by Burke et al, in which the most common self-reported symptoms included bone/joint pain and head/neck symptoms including headache, vision change, and hearing change (77.6% each). (more…)
Could Sugar replace Gadolinium-Based Contrast Agents used for MRIs?
Animal studies have shown that D-glucose is a potential biodegradable MRI contrast agent for imaging glucose uptake in tumors. According to findings reported by Xu et al in “Dynamic Glucose-Enhanced (DGE) MRI: Translation to Human Scanning and First Results in Glioma Patients”, dynamic glucose-enhanced (DGE) imaging is feasible in humans. Chemical exchange saturation transfer (CEST) MRI was used to image dynamic signal changes in the human brain at 7 Tesla (7T) during and after infusion of D-glucose (sugar).
DGE image data from 4 normal volunteers and 3 glioma patients showed strong signal enhancement in blood vessels, while the enhancement varied spatially over the tumor. The authors noted that the areas of enhancement differed spatially between DGE and conventional Gd-enhanced imaging, suggesting complementary image information content for these two types of agents.
The researchers concluded that it was possible to detect water signal changes in the human brain induced by infusion of D-glucose. They said that the signal changes are due to glucose uptake in vessels, the brain and tumor tissue areas, and are related to the kinetics of delivery, transport and metabolism of D-glucose. They noted that an interesting finding is that different tumor areas showed varying times of enhancement, which suggests that the dynamic time curves may contain information about blood-brain barrier (BBB) permeability.
According to the study authors, a larger human study is needed, and for DGE to become relevant clinically, it would have to be possible at 3 Tesla and preferably also at 1.5 Tesla.
Why this is important for patients – (more…)
Gadolinium Deposition Disease – Part of a Family of Disorders
Important News for Patients who have retained gadolinium –
A recently published article by UNC Radiologist Dr. Richard Semelka and his colleagues proposes naming the histopathologically proven presence of gadolinium in brain tissue “gadolinium storage condition”, and it describes a new entity that represents symptomatic deposition of gadolinium in individuals with normal renal function, for which they propose the designation “gadolinium deposition disease”. The article titled: Gadolinium in Humans: A Family of Disorders, was published in AJR online.
The article is not freely available to the public at this time. Because of that, I will provide some important information from the article for patients and their doctors below.
Gadolinium Storage Condition –
“Gadolinium storage condition” is the term proposed for gadolinium tissue deposition. The authors said, “Even in patients with normal renal function, in vivo clinical exposure to gadolinium chelates results in gadolinium incorporation into body tissues such as bone matrix or brain tissues.” (See references below.)
It appears that gadolinium accumulation varies depending on the stability of the agent used. As with NSF, the least stable GBCAs appear to be most likely to result in gadolinium storage condition, and stable agents either do not cause it or cause it at a very low level. The clinical significance of gadolinium tissue deposition remains incompletely understood.
Gadolinium Deposition Disease –
“Gadolinium deposition disease” is the name proposed for a disease process observed in subjects with normal or near normal renal function who develop persistent symptoms that arise hours to 2 months after the administration of gadolinium-based contrast agents (GBCAs). In these cases, no preexistent disease or subsequently developed disease of an alternate known process is present to account for the symptoms.
The authors note that some of these patients are likely to have coexistent gadolinium storage condition, as described above, but gadolinium deposition disease is also described after a single administration of GBCA. The causal relationship has not been fully established, but it is under investigation.
The article references our MRI Gadolinium-Toxicity support group and notes that the group has reported symptoms it considers to be consistent with the known toxic effects of gadolinium. They also cite the results of our 2014 Symptom Survey which suggests an association between chronic effects and GBCA exposure.
The authors said, in their experience, “Symptoms of gadolinium deposition disease are similar but not identical to those observed in NSF”. They said that their preliminary investigation has convinced them that this phenomenon is a true disease process. (more…)
Gadolinium Toxicity 