Ischemic Stroke Increased Gadolinium Deposition in the Brain and Aggravated Astrocyte Injury After Gadolinium-Based Contrast Agent Administration: Linear Versus Macrocyclic Agents

Background: Gadolinium (Gd)-based contrast agents (GBCAs) have been widely used in MRI. However, several studies have reported Gd deposition in the brain, which has raised concerns about safety.

Purpose: To investigate the effects of ischemic stroke on Gd deposition in the brain after repeated administration of linear or macrocyclic GBCAs and to determine whether GBCAs aggravate astrocyte injury after stroke.

Study type: Animal study.

Animal model: Twenty-seven male Sprague-Dawley rats were randomized to an exposure group (n = 24) and a healthy control group (n = 3). Half of the exposure group (n = 12) underwent transient middle cerebral artery occlusion (tMCAO) and half (n = 12) had a sham procedure. In each subgroup (tMCAO or sham), the rats had repeated gadopentetate (n = 6) or gadobutrol (n = 6) injections. Oxygen-glucose deprivation and reoxygenation (OGD/R) was used as an in vitro model of stroke.

Assessment: On day 3 and day 28 after the last injection (p.i.), the Gd concentration in the cerebrum was quantified by inductively coupled plasma mass spectrometry. Cell viability, Reactive Oxygen Species (ROS), and mitochondrial membrane potential (MMP) were analyzed in vitro.

Statistical tests: One-way analysis of variance and two-sample t-tests were performed.

Results: The Gd concentration in the ipsilateral hemisphere homogenates of tMCAO group was significantly higher than that in the brain homogenates of the sham group on day 3 p.i. of either gadobutrol (0.065 ± 0.006 vs. 0.042 ± 0.007 μg/g, P < 0.05) or gadopentetate (0.093 ± 0.010 vs. 0.069 ± 0.008 μg/g, P < 0.05). Increased Gd deposition was also found in the ipsilateral hemisphere homogenates of the tMCAO group compared with the brain homogenates of the sham group on day 28 p.i. of gadopentetate (0.075 ± 0.012 vs. 0.044 ± 0.003 μg/g, P < 0.05), but not gadobutrol (0.012 ± 0.007 vs. 0.010 ± 0.001 μg/g, P = 0.80). The Gd concentration in the ipsilateral hemisphere in the tMCAO group was significantly higher for gadopentetate than gadobutrol on both day 3 p.i. (0.085 ± 0.006 vs. 0.049 ± 0.005 μg/g, P < 0.05) and day 28 p.i (0.075 ± 0.012 vs. 0.012 ± 0.007 μg/g, P < 0.05). Additionally, compared with gadobutrol, gadopentetate decreased viability, increased ROS accumulation, and decreased MMP in OGD/R-induced astrocytes (all P < 0.05).

Data conclusion: Administration of GBCAs after an animal model of ischemic stroke increased Gd deposition in the brain and aggravated astrocyte injury. The effect of gadopentetate appeared to be more pronounced than that of gadobutrol.