Spatially resolved quantification of gadolinium deposited in the brain of a patient treated with gadolinium-based contrast agents

Stefanie Fingerhut; Ann-Christin Niehoff; Michael Sperling; Astrid Jeibmann; Werner Paulus; Thomas Niederstadt; Thomas Allkemper; Walter Heindel; Markus Holling; Uwe Karst

doi:10.1016/j.jtemb.2017.10.004

Spatially resolved quantification of gadolinium deposited in the brain of a patient treated with gadolinium-based contrast agents

J Trace Elem Med Biol. 2018 Jan:45:125-130. doi: 10.1016/j.jtemb.2017.10.004. Epub 2017 Oct 13.

Authors

Affiliations

¹ Institute of Inorganic and Analytical Chemistry, University of Münster, Corrensstraße 30, 48149 Münster, Germany.
² Institute of Inorganic and Analytical Chemistry, University of Münster, Corrensstraße 30, 48149 Münster, Germany; European Virtual Institute for Speciation Analysis (EVISA), Mendelstraße 11, 48149 Münster, Germany.
³ Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149 Münster, Germany. Electronic address: Astrid.Jeibmann@ukmuenster.de.
⁴ Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149 Münster, Germany.
⁵ Department of Clinical Radiology, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany.
⁶ Department of Neurosurgery, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany.
⁷ Institute of Inorganic and Analytical Chemistry, University of Münster, Corrensstraße 30, 48149 Münster, Germany. Electronic address: uk@uni-muenster.de.

PMID: 29173468
DOI: 10.1016/j.jtemb.2017.10.004

Abstract

Due to its paramagnetic properties resulting from seven unpaired f-electrons, Gd is frequently applied in magnetic resonance imaging examinations. Due to the acute toxicity of free Gd³⁺, ligand ions based on polyaminocarboxylic acids are used to create thermodynamically stable linear or macrocyclic complexes. The highly water soluble Gd-based contrast agents (GBCAs) are known to be excreted fast and unmetabolized, mostly via the kidneys. Nevertheless, recent studies showed that Gd traces persists not only in animal but also in human brain. Aim of this study was the development and application of an analytical method for the spatially resolved quantification of gadolinium traces in human brain thin sections of a patient treated with GBCAs. For this retrospective study different human brain regions were selected to analyze the distribution of gadolinium. An additional patient served as control sample, as no GBCA was administered. Deep-frozen brain thin sections were analyzed by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) and matrix-matched gelatin standards were prepared to quantify the gadolinium deposits via an external calibration. LA-ICP-MS analyses with high spatial resolution showed gadolinium deposits in different brain regions with highest concentrations above 800ngg^-1 more than two years after the last application of a GBCA. An excellent limit of quantification of 7ngg^-1, which is far below the limits of detection of MRI methods, could be achieved. The found concentrations confirm recent reports on gadolinium depositions in human brain, which were obtained without high spatial resolution. LA-ICP-MS provides limits of quantification, which are well suited to detect ultratrace amounts of gadolinium in human brain. Therefore, it provides valuable information on the distribution of gadolinium traces in the human brain even after single administration of GBCAs.

Keywords: Gadodiamide; Gadolinium retention; Human brain; LA-ICP-MS; Quantification.

MeSH terms

Brain / metabolism*
Contrast Media / chemistry*
Contrast Media / metabolism*
Gadolinium / chemistry*
Gadolinium / metabolism*
Humans
Magnetic Resonance Imaging
Mass Spectrometry

Substances

Contrast Media
Gadolinium