Francesca Arena1,2, Paola Bardini3,4, Francesco Blasi5, Eliana Gianolio3, Giada M Marini3,4, Francesca La Cava3,4, Giovanni Valbusa6, Silvio Aime3,7. 1. Department of Molecular Biotechnology and Health Sciences, University of Torino (Italy), via Nizza 52, 10126, Torino, Italy. francesca.arena@unito.it. 2. Department of Molecular Biotechnology and Health Sciences, Centro di Eccellenza di Imaging Preclinico (CEIP)- University of Torino (Italy), c/o BioIndustry Park of Canavese, Via Ribes 5, 10010, Colleretto Giacosa, TO, Italy. francesca.arena@unito.it. 3. Department of Molecular Biotechnology and Health Sciences, University of Torino (Italy), via Nizza 52, 10126, Torino, Italy. 4. Department of Molecular Biotechnology and Health Sciences, Centro di Eccellenza di Imaging Preclinico (CEIP)- University of Torino (Italy), c/o BioIndustry Park of Canavese, Via Ribes 5, 10010, Colleretto Giacosa, TO, Italy. 5. Bracco Research Centre, Bracco Imaging SpA, Via Ribes 5, 10010, Colleretto Giacosa, TO, Italy. 6. Ephoran Imaging Solutions S.r.l., c/o BioIndustry Park of Canavese, Via Ribes 5, 10010, Colleretto Giacosa, TO, Italy. 7. IBB-CNR, Sede secondaria c/o MBC, Via Nizza 52, 10126, Torino, Italy.
Abstract
PURPOSE: The discussed topic about gadolinium-based contrast agents (GBCA) safety has recently been revived due to the evidence of hyperintensities observed in the dentate nucleus (DN) and globus pallidus (GP) in the brain of patients with normal kidney function. Several preclinical studies have been conducted to understanding how the use of GBCAs can promote the gadolinium deposition in the brain. Here, we evaluate the impact of chronic cerebral hypoperfusion on gadolinium presence. METHODS: T1 hyperintensities and BBB integrity were evaluated by MRI in chronically hypoperfused and healthy rats injected with either gadodiamide or hypertonic saline. Additionally, the assessment of glucose metabolism by PET imaging and the gadolinium content by ICP-MS was performed after the last MR scan. RESULTS: Chronically hypoperfused rats displayed a greater MRI T1w signal in the DCN and hippocampus compared to Sham-operated animals, suggesting gadolinium accumulation. Dynamic contrast-enhanced (DCE) MRI assessment of BBB permeability revealed loss of integrity (high Ktrans) after rat injury in the dentate nuclei and hippocampus. Ex vivo tissue analysis showed greater gadolinium retention in the cerebellum and subcortical regions, supporting the imaging finding. FDG-PET imaging of the cerebellum did not reveal abnormal uptake in the DCN after chronic cerebral hypoperfusion. CONCLUSION: Higher signal intensity followed by higher Gd concentration observed in DCN and hippocampus of animals subjected to cerebral injury can be associated with an increase in BBB permeability due to the applied vascular dementia animal model. Nonetheless, no glucose metabolism abnormalities were detected in chronically hypoperfused cerebellum.
PURPOSE: The discussed topic about gadolinium-based contrast agents (GBCA) safety has recently been revived due to the evidence of hyperintensities observed in the dentate nucleus (DN) and globus pallidus (GP) in the brain of patients with normal kidney function. Several preclinical studies have been conducted to understanding how the use of GBCAs can promote the gadolinium deposition in the brain. Here, we evaluate the impact of chronic cerebral hypoperfusion on gadolinium presence. METHODS: T1 hyperintensities and BBB integrity were evaluated by MRI in chronically hypoperfused and healthy rats injected with either gadodiamide or hypertonic saline. Additionally, the assessment of glucose metabolism by PET imaging and the gadolinium content by ICP-MS was performed after the last MR scan. RESULTS: Chronically hypoperfused rats displayed a greater MRI T1w signal in the DCN and hippocampus compared to Sham-operated animals, suggesting gadolinium accumulation. Dynamic contrast-enhanced (DCE) MRI assessment of BBB permeability revealed loss of integrity (high Ktrans) after rat injury in the dentate nuclei and hippocampus. Ex vivo tissue analysis showed greater gadolinium retention in the cerebellum and subcortical regions, supporting the imaging finding. FDG-PET imaging of the cerebellum did not reveal abnormal uptake in the DCN after chronic cerebral hypoperfusion. CONCLUSION: Higher signal intensity followed by higher Gd concentration observed in DCN and hippocampus of animals subjected to cerebral injury can be associated with an increase in BBB permeability due to the applied vascular dementia animal model. Nonetheless, no glucose metabolism abnormalities were detected in chronically hypoperfused cerebellum.
Authors: Muzaimi Mustapha; Che Mohd Nasril Che Mohd Nassir; Niferiti Aminuddin; Amanina Ahmad Safri; Mazira Mohamad Ghazali Journal: Front Physiol Date: 2019-10-24 Impact factor: 4.566