Purpose: The human cerebrospinal fluid (CSF) changes completely every 6 hours. Human microglia is one of the slowest dividing immune cells. The main goal is to find the cause of everlasting gadolinium (Gd) persistence in CSF of paediatric cancer survivors after GBCA. Methods or Background: Study group: 68 paediatric patients with haematological malignancies with Dotarem-enhanced MRI, underwent lumbar puncture. Control group: 47 paediatric patients with haematological malignancies, never exposed to the GBCA, underwent lumbar puncture. CSF samples of both groups were analysed for gadolinium, iron and ferritin concentration. In vitro siderotic and control human oligodendrocyte (HOG) cell line models were developed and cultured with calcein-labeled Dotarem. Intracellular amount of Gd and iron in both cell lines was performed by ICP-Mass Spectrometry. Single-cell uptake of Dotarem was performed using confocal fluorescence microscopy. Results or Findings: The mean number of Gd-enhanced MRI was 1.8 (1 – 8). The mean interval between the last MRI and lumbar puncture was 2.8 (0.3 – 12) years. Mean (± SD) CSF Gd concentration was 0.065 (0.199) μg/L. We detected 0.001 μg/L Gd concentration in the CSF of the patients who had undergone a single Gd-enhanced MRI 12 years before the lumbar puncture. We found differences (p<0.05) comparing CSF Gd concentration in low, moderate and severe systemic siderosis. We confirmed that Gd deposition in glia increased in iron overload. We documented transmembrane passage of gadolinium in two glial cells lines, with and without iron overload. Conclusion: Neurodegenerative diseases have been increasingly diagnosed in paediatric patients in recent years. Gd brain storage along with other metals such as iron could accelerate the onset of degenerative symptoms. Limitations: The fact that this was a singlecentre study, the paediatric population, as well as the small sample number were identified as limitations. Ethics committee approval: This study was approved by the bioethics committee of IRCCS Burlo Garofolo Trieste (reference no. 1105/2015). Funding for this study: No funding was received for this study.

Gadolinium-based contrast agents can cross non-nervous cell membranes rather than remain confined to the extracellular compartment of the central nervous system / Zennaro, F. F.; Sala, R.; Covino, C.; Zampieri, D.; Zanon, D.; Crosera, M.; Maximova, N.. - In: INSIGHTS INTO IMAGING. - ISSN 1869-4101. - 13:(2022), pp. 1812-10.335-1812-10.335. (Intervento presentato al convegno ECR 2022 tenutosi a Vienna nel 13-17 July 2022) [10.1186/s13244-022-01337-x].

Gadolinium-based contrast agents can cross non-nervous cell membranes rather than remain confined to the extracellular compartment of the central nervous system

R. Sala;
2022-01-01

Abstract

Purpose: The human cerebrospinal fluid (CSF) changes completely every 6 hours. Human microglia is one of the slowest dividing immune cells. The main goal is to find the cause of everlasting gadolinium (Gd) persistence in CSF of paediatric cancer survivors after GBCA. Methods or Background: Study group: 68 paediatric patients with haematological malignancies with Dotarem-enhanced MRI, underwent lumbar puncture. Control group: 47 paediatric patients with haematological malignancies, never exposed to the GBCA, underwent lumbar puncture. CSF samples of both groups were analysed for gadolinium, iron and ferritin concentration. In vitro siderotic and control human oligodendrocyte (HOG) cell line models were developed and cultured with calcein-labeled Dotarem. Intracellular amount of Gd and iron in both cell lines was performed by ICP-Mass Spectrometry. Single-cell uptake of Dotarem was performed using confocal fluorescence microscopy. Results or Findings: The mean number of Gd-enhanced MRI was 1.8 (1 – 8). The mean interval between the last MRI and lumbar puncture was 2.8 (0.3 – 12) years. Mean (± SD) CSF Gd concentration was 0.065 (0.199) μg/L. We detected 0.001 μg/L Gd concentration in the CSF of the patients who had undergone a single Gd-enhanced MRI 12 years before the lumbar puncture. We found differences (p<0.05) comparing CSF Gd concentration in low, moderate and severe systemic siderosis. We confirmed that Gd deposition in glia increased in iron overload. We documented transmembrane passage of gadolinium in two glial cells lines, with and without iron overload. Conclusion: Neurodegenerative diseases have been increasingly diagnosed in paediatric patients in recent years. Gd brain storage along with other metals such as iron could accelerate the onset of degenerative symptoms. Limitations: The fact that this was a singlecentre study, the paediatric population, as well as the small sample number were identified as limitations. Ethics committee approval: This study was approved by the bioethics committee of IRCCS Burlo Garofolo Trieste (reference no. 1105/2015). Funding for this study: No funding was received for this study.
2022
Gadolinium-based contrast agents can cross non-nervous cell membranes rather than remain confined to the extracellular compartment of the central nervous system / Zennaro, F. F.; Sala, R.; Covino, C.; Zampieri, D.; Zanon, D.; Crosera, M.; Maximova, N.. - In: INSIGHTS INTO IMAGING. - ISSN 1869-4101. - 13:(2022), pp. 1812-10.335-1812-10.335. (Intervento presentato al convegno ECR 2022 tenutosi a Vienna nel 13-17 July 2022) [10.1186/s13244-022-01337-x].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2944911
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