Gadolinium Toxicity

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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…)

Patients with meningioma have increased T1 hyperintensity after multiple contrast-enhanced MRI

On March 11, 2015, a retrospective study on 46 patients with a meningioma who had routinely undergone follow-up enhanced-MRI scans with gadodiamide was published online in Investigative Radiology.  The authors report a significant increase in T1 hyperintensity of the dentate nuclei of the cerebellum on unenhanced scans was observed between the first and last MRI in the group of patients with a history of at least 6 enhanced MRI.  All patients had normal renal function before intravenous administration of gadodiamide (Omniscan).

Two recent studies (Kanda and Errante), with different cohorts of patients, have shown the association between high T1 signal intensity of the dentate nucleus and history of a high number of contrast-enhanced MRI in patients with cancer and brain metastases, and in patients with Multiple Sclerosis (MS). (more…)

Is history repeating itself? Are Gadolinium-Based Contrast Agents the next Thorotrast?

While doing research in early 2012, I came across a 2007 article written by J.F.M. Wetzels of The Netherlands that really caused me to pause and think about the problems associated with Gadolinium-Based Contrast Agents.  The title was Thorotrast toxicity: the safety of Gadolinium compounds”.  Thorotrast was a radiocontrast agent used from 1930 to 1960.  It wasn’t until the late 1940’s that the first “Thorotrast-related malignancies” were described in the literature and the problem came to light.

Thorotrast particles had been deposited in cells in the liver, spleen, bone marrow, and lymph nodes where they stayed and continually exposed the surrounding tissue to radiation.  The problems created by Thorotrast had such a long-latency period that malignancies might not show up for 45 years or more later.

Wetzels described what was happening with Gadolinium and NSF through 2006.  He said that because Gadolinium is a toxic, heavy metal, “Gadolinium-Based Contrast Agents are all chelates, which must ensure that no free Gadolinium is present in the circulation”.  Wetzels closed by saying, “we must keep in mind that toxic effects may occur less frequently, later, and only after repeated exposure in patients with less severe renal dysfunction”.  When I read that, I thought of what might be happening to patients with normal renal function.  (more…)

Study reports brain abnormalities on MRI in patients with normal kidney function

In the October 2014 issue of Investigative Radiology, Errante et al report study findings that confirm the association between the increase in the unenhanced T1-weighted signal intensity of the dentate nucleus and the number of gadolinium-enhanced MRI scans.  (The dentate nucleus is located within the deep white matter of the brain.)

The study included 38 patients with Multiple Sclerosis (MS) and 37 patients with brain metastases (BMs) who had undergone at least 2 consecutive enhanced MRIs.  After calculating the dentate nuclei-to-pons (DNP) signal intensity ratio, these values were compared between patients with less than 6 and those with 6 or more contrast-enhanced MRI.  A progressive increase in the T1 signal intensity of the DNP ratio was observed in both the MS group and the BM group.  All patients had normal kidney function. (more…)

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