Gadolinium Deposition in Human Brain Tissues after Contrast-enhanced MR Imaging in Adult Patients without Intracranial Abnormalities

Abstract

Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group). All patients in the contrast group had received gadodiamide. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy with energy-dispersive x-ray spectroscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Results Tissues from the four neuroanatomic regions of gadodiamide-exposed patients contained 0.1-19.4 μg of gadolinium per gram of tissue in a statistically significant dose-dependent relationship (globus pallidus: ρ = 0.90, P = .04). In contradistinction, patients in the control group had undetectable levels of gadolinium with ICP-MS. All patients had normal brain pathologic characteristics at autopsy. Three patients in the contrast group had borderline renal function (estimated glomerular filtration rate <45 mL/min/1.73 m) and hepatobiliary dysfunction at MR examination. Gadolinium deposition in the contrast group was localized to the capillary endothelium and neuronal interstitium and, in two cases, within the nucleus of the cell. Conclusion Gadolinium deposition in neural tissues after GBCA administration occurs in the absence of intracranial abnormalities that might affect the permeability of the blood-brain barrier. These findings challenge current understanding of the biodistribution of these contrast agents and their safety. RSNA, 2017.

Absence of dentate nucleus resting‐state functional connectivity changes in nonneurological patients with gadolinium‐related hyperintensity on T1‐weighted images

“…H IGH SIGNAL INTENSITY of deep cerebellar and deep brain nuclei on unenhanced T 1 -weighted images [1][2][3][4][5][6][7] as well as changes of T 1 relaxometry values 8 may reflect the presence of long-term retained or deposited gadolinium in the brain [9][10][11] in patients exposed to cumulative doses of gadolinium-based contrast agents (GBCAs). In the cerebellum, the dentate nuclei (DN) and the cortex are the areas where gadolinium predominantly retains and/or accumulates.…”

3D‐ASL perfusion correlates with VEGF expression and overall survival in glioma patients: Comparison of quantitative perfusion and pathology on accurate spatial location‐matched basis

“…However, the most extensively administered gadolinium‐based MR contrast material has shown dose‐dependent cumulative deposition in neural tissue in patients without severe renal disfunction . Correlative neurotoxicity remains undefined . In addition, contraindications to the use of contrast media limit application of current perfusion‐based techniques in patients with renal disease or allergy to gadolinium.…”

One‐step analysis of brain perfusion and function for acute stroke patients after reperfusion: A resting‐state fMRI study

“…Dynamic susceptibility contrast perfusion‐weighted imaging (DSC‐PWI) is the most commonly used imaging technique in clinical practice. However, recent studies have sparked awareness of gadolinium (Gd) deposition in the brain and Gd contrast, which was found to have a positive association with the development of nephrogenic systemic fibrosis (NSF) . The severe potential side effects of contrast agents limit the number of repeated scans one patient may undergo and demand noncontrast alternatives.…”