Rasschaert, Marlene and Schroeder, Josef A. and Wu, Ting-Di and Marco, Sergio and Emerit, Andrea and Siegmund, Heiko and Fischer, Claudia and Fretellier, Nathalie and Idee, Jean-Marc and Corot, Claire and Brochhausen, Christoph and Guerquin-Kern, Jean-Luc (2018) Multimodal Imaging Study of Gadolinium Presence in Rat Cerebellum Differences Between Gd Chelates, Presence in the Virchow-Robin Space, Association With Lipofuscin, and Hypotheses About Distribution Pathway. INVESTIGATIVE RADIOLOGY, 53 (9). pp. 518-528. ISSN 0020-9996, 1536-0210
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Purpose: The aim of this study was to investigate, based on in-depth multimodal imaging, the presence of Gd deposits, their ultrastructure, location, and co-location with endogenous elements, in the cerebellum, after repeated administrations of gadolinium-based contrast agents (GBCAs). Methods: Rats sensitized by subtotal nephrectomy received 20 daily intravenous injections of 0.6 mmol Gd/kg for 5 weeks of commercial forms of either gadoterate, gadobenate or gadodiamide, or saline (n = 2/group). The study was randomized and blinded. Magnetic resonance imaging examination was performed weekly. One month after the last injection, electron microscopy analysis of the deep cerebellar nuclei, the granular layer of cerebellar cortex, and the choroid plexus was performed. Elemental analysis of deposits was carried out by electron energy loss spectroscopy. Secondary ion mass spectroscopy was used for complementary chemical mapping. Results: A T1 hypersignal was evidenced in the deep cerebellar nuclei of rats treated with linear GBCAs, and Gd deposits were identified in all the studied cerebellar structures with gadobenate and gadodiamide (except in the granular layer in gadobenate-treated rats). No such effect was found with the macrocyclic GBCA gadoterate. Most of the Gd deposits revealed a characteristic spheroid sea urchin-like morphology, rich in phosphorus, and were localized in the basal lamina of microvessels, in the perivascular Virchow-Robin space, and in the interstitium. Gd was also identified in the glial cells, associated with lipofuscin pigments, for these same groups. Conclusions: Transmission electron microscopy analysis of cerebellums of renally impaired rats repeatedly injected with gadobenate and gadodiamide revealed the presence of Gd. Spheroid Gd depositions consisting of a filamentous meshwork were observed in the wall of microvessels, in perivascular Virchow-Robin space, and in the interstitium. Gd was also found in choroid plexus and was associated with pigments (likely lipofuscin) in glial cells. This is consistent with the involvement of the glymphatic distribution pathway for GBCAs. No insoluble Gd deposits were detected in rats injected with the macrocyclic GBCA gadoterate and controls.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NEPHROGENIC SYSTEMIC FIBROSIS; STAGE RENAL-DISEASE; CONTRAST AGENTS; CEREBROSPINAL-FLUID; HEALTHY RATS; BRAIN; DEPOSITION; ELECTRON; GADODIAMIDE; CLEARANCE; deep cerebellar nuclei; cerebellar cortex; choroid plexus; glymphatic pathway; electron microscopy; secondary ion mass spectroscopy; gadolinium presence; gadodiamide; gadobenate; gadoterate |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Jan 2020 15:26 |
| Last Modified: | 09 Jan 2020 15:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14002 |
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