Alexander Radbruch1,2, Henning Richter3,4, Stefanie Fingerhut5, Louise Francoise Martin3,4, Anna Xia6, Niklas Henze6, Werner Paulus6, Michael Sperling5, Uwe Karst5, Astrid Jeibmann6. 1. From the Department of Diagnostic and Interventional Radiology and Neuroradiology, University Clinic Essen, Essen. 2. German Cancer Research Center, Department of Radiology, Heidelberg, Germany. 3. Diagnostic Imaging Research Unit, Clinic for Diagnostic Imaging, Department of Clinical Diagnostics and Services. 4. Clinic for Zoo Animals, Exotic Pets and Wildlife, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. 5. Institute of Inorganic and Analytical Chemistry, University of Münster. 6. Institut of Neuropathology, Pottkamp 2, University Hospital Münster, Münster, Germany.
Abstract
OBJECTIVE: Recent studies reported a signal intensity increase in the deep cerebellar nuclei (DCN) on magnetic resonance images caused by gadolinium deposition after the injection of gadolinium-based contrast agents (GBCAs). There is an ongoing debate if the propensity of a GBCA to deposit gadolinium is primarily determined by its class as either linear or macrocyclic. In the current study, we aimed to compare the amount and the distribution of retained gadolinium of linear and macrocyclic GBCAs in the DCN after a single injection at a dose comparable to a human patient's in a large animal model. MATERIALS AND METHODS: Eighteen sheep were randomly assigned in 6 groups of 3 animals, which received a single injection of 0.1 mmol/kg body weight of either the macrocyclic GBCAs gadobutrol, gadoteridol, or gadoterate meglumine; the linear GBCAs gadobenate dimeglumine or gadodiamide; or saline. Animals were euthanized 10 weeks after injection. Local distribution and concentration of gadolinium and colocalization to other metals (iron, zinc, copper) in the DCN was assessed by laser ablation-inductively coupled plasma-mass spectrometry. RESULTS: Average gadolinium concentration for the macrocyclic GBCAs and the saline group was below the limit of quantification (5.7 ng/g tissue). In contrast, 14 (for gadobenate) and 27 (for gadodiamide) times more gadolinium than the limit of quantification was found for the linear GBCAs gadobenate (mean, 83 ng/g) or gadodiamide (mean, 155 ng/g brain tissue). Gadolinium distribution colocalized with other metals for linear GBCAs and a specific accumulation in the DCN was found. DISCUSSION: The current study supports the hypothesis that the amount of gadolinium deposited in the brain is primarily determined by its class as either macrocyclic or linear. The accumulation of gadolinium in the DCN for linear GBCAs explains the hyperintensities in the DCN found in previous patient studies with linear GBCAs.
OBJECTIVE: Recent studies reported a signal intensity increase in the deep cerebellar nuclei (DCN) on magnetic resonance images caused by gadolinium deposition after the injection of gadolinium-based contrast agents (GBCAs). There is an ongoing debate if the propensity of a GBCA to deposit gadolinium is primarily determined by its class as either linear or macrocyclic. In the current study, we aimed to compare the amount and the distribution of retained gadolinium of linear and macrocyclic GBCAs in the DCN after a single injection at a dose comparable to a humanpatient's in a large animal model. MATERIALS AND METHODS: Eighteen sheep were randomly assigned in 6 groups of 3 animals, which received a single injection of 0.1 mmol/kg body weight of either the macrocyclic GBCAsgadobutrol, gadoteridol, or gadoterate meglumine; the linear GBCAsgadobenate dimeglumine or gadodiamide; or saline. Animals were euthanized 10 weeks after injection. Local distribution and concentration of gadolinium and colocalization to other metals (iron, zinc, copper) in the DCN was assessed by laser ablation-inductively coupled plasma-mass spectrometry. RESULTS: Average gadolinium concentration for the macrocyclic GBCAs and the saline group was below the limit of quantification (5.7 ng/g tissue). In contrast, 14 (for gadobenate) and 27 (for gadodiamide) times more gadolinium than the limit of quantification was found for the linear GBCAs gadobenate (mean, 83 ng/g) or gadodiamide (mean, 155 ng/g brain tissue). Gadolinium distribution colocalized with other metals for linear GBCAs and a specific accumulation in the DCN was found. DISCUSSION: The current study supports the hypothesis that the amount of gadolinium deposited in the brain is primarily determined by its class as either macrocyclic or linear. The accumulation of gadolinium in the DCN for linear GBCAs explains the hyperintensities in the DCN found in previous patient studies with linear GBCAs.
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