TY - JOUR A1 - Anderhalten, L. A1 - Silva, R. V. A1 - Morr, A. A1 - Wang, S. A1 - Smorodchenko, A. A1 - Saatz, Jessica A1 - Traub, Heike A1 - Mueller, S. A1 - Boehm-Sturm, P. A1 - Rodriguez-Sillke, Y. A1 - Kunkel, D. A1 - Hahndorf, J. A1 - Paul, F. A1 - Taupitz, M. A1 - Sack, I. A1 - Infante-Duarte, C. T1 - Different Impact of Gadopentetate and Gadobutrol on Inflammation-Promoted Retention and Toxicity of Gadolinium Within the Mouse Brain N2 - Objectives: Using a murine model of multiple sclerosis, we previously showed that repeated administration of gadopentetate dimeglumine led to retention of gadolinium (Gd) within cerebellar structures and that this process was enhanced with inflammation. This study aimed to compare the kinetics and retention profiles of Gd in inflamed and healthy brains after application of the macrocyclic Gd-based contrast agent (GBCA) gadobutrol or the linear GBCA gadopentetate. Moreover, potential Gd-induced neurotoxicity was investigated in living hippocampal slices ex vivo. Materials and Methods: Mice at peak of experimental autoimmune encephalomyelitis (EAE; n = 29) and healthy control mice (HC; n = 24) were exposed to a cumulative dose of 20 mmol/kg bodyweight of either gadopentetate dimeglumine or gadobutrol (8 injections of 2.5 mmol/kg over 10 days). Magnetic resonance imaging (7 T) was performed at baseline as well as at day 1, 10, and 40 post final injection (pfi) of GBCAs. Mice were sacrificed after magnetic resonance imaging and brain and blood Gd content was assessed by laser ablation-inductively coupled plasma (ICP)-mass spectrometry (MS) and ICP-MS, respectively. In addition, using chronic organotypic hippocampal slice cultures, Gd-induced neurotoxicity was addressed in living brain tissue ex vivo, both under control or inflammatory (tumor necrosis factor α [TNF-α] at 50 ng/μL) conditions. Results: Neuroinflammation promoted a significant decrease in T1 relaxation times after multiple injections of both GBCAs as shown by quantitative T1 mapping of EAE brains compared with HC. This corresponded to higher Gd retention within the EAE brains at 1, 10, and 40 days pfi as determined by laser ablation-ICP-MS. In inflamed cerebellum, in particular in the deep cerebellar nuclei (CN), elevated Gd retention was observed until day 40 after last gadopentetate application (CN: EAE vs HC, 55.06 ± 0.16 μM vs 30.44 ± 4.43 μM). In contrast, gadobutrol application led to a rather diffuse Gd content in the inflamed brains, which strongly diminished until day 40 (CN: EAE vs HC, 0.38 ± 0.08 μM vs 0.17 ± 0.03 μM). The analysis of cytotoxic effects of both GBCAs using living brain tissue revealed an elevated cell death rate after incubation with gadopentetate but not gadobutrol at 50 mM. The cytotoxic effect due to gadopentetate increased in the presence of the inflammatory mediator TNF-α (with vs without TNF-α, 3.15% ± 1.18% vs 2.17% ± 1.14%; P = 0.0345). Conclusions: In the EAE model, neuroinflammation promoted increased Gd retention in the brain for both GBCAs. Whereas in the inflamed brains, efficient clearance of macrocyclic gadobutrol during the investigated time period was observed, the Gd retention after application of linear gadopentetate persisted over the entire observational period. Gadopentetate but not gadubutrol appeared to be neurotoxic in an ex vivo paradigm of neuronal inflammation. KW - Imaging KW - ICP-MS KW - Gadolinium KW - Contrast agent KW - Laser ablation KW - Brain KW - Multiple sclerosis PY - 2022 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-546910 DO - https://doi.org/10.1097/RLI.0000000000000884 SN - 0020-9996/22/0000–0000 VL - 57 IS - 10 SP - 677 EP - 688 PB - Wolters Kluwer N.V. CY - Alphen aan den Rijn, The Netherlands AN - OPUS4-54691 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Bayerl, C. A1 - Shahryari, M. A1 - Reiter, R. A1 - Proß, V. A1 - Lehmann, K. A1 - Kühl, A. A. A1 - Becker, Dorit A1 - Schulz, Andreas A1 - Infante Duarte, C. A1 - Taupitz, M. A1 - Geisel, D. A1 - Tzschätzsch, H. A1 - Saatz, Jessica A1 - Traub, Heike A1 - Asbach, P. T1 - Quantitative Analysis of Gadolinium Deposits in Liver Tissue of Patients After Single or Multiple Gadolinium-based Contrast Agent Application N2 - Gadolinium-based contrast agents (GBCAs) are widely used in magnetic resonance imaging. Concerns exist regarding gadolinium deposition and its potential histopathologic tissue alterations, especially after repeated administrations of linear, less stable GBCAs. This study aimed to quantify gadolinium mass fractions in liver specimens of subjects exposed to GBCAs in correlation with histopathologic features. In this study, mass fractions of gadolinium in human liver specimens from 25 subjects who underwent liver tumor resection surgery and had received GBCA (1 to 9 times over 4 years), were quantitatively analyzed using inductively coupled plasma–mass spectrometry (ICP-MS). Histomorphology was assessed based on the nonalcoholic fatty liver disease activity score (NAS). Our results suggest that after intravenous administration of GBCA, a small fraction of gadolinium is retained in the liver over a time period of at least several weeks. A relationship was observed between Gadolinium retention and the number of GBCA administrations, but not with the cumulative dose and the degree of fatty liver disease. KW - ICP-MS KW - Contrast agent KW - Gadolinium KW - Liver PY - 2025 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-646608 DO - https://doi.org/10.1097/RLI.0000000000001254 SN - 1536-0210 SP - 1 EP - 10 PB - Lippincott Williams & Wilkins CY - Philadelphia, Pa. AN - OPUS4-64660 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -