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T1-Weighted Hypersignal in the Deep Cerebellar Nuclei After Repeated Administrations of Gadolinium-Based Contrast Agents in Healthy Rats: Difference Between Linear and Macrocyclic Agents.

Robert P, Lehericy S, Grand S, Violas X, Fretellier N, Idée JM, Ballet S, Corot C - Invest Radiol (2015)

Bottom Line: The DCN-to-cerebellar cortex signal ratio was significantly increased from the 12th injection of gadodiamide (1.070 ± 0.024) compared to the gadoterate meglumine group (1.000 ± 0.033; P < 0.001) and control group (1.019 ± 0.022; P < 0.001) and did not significantly decrease during the treatment-free period.Total Gd concentrations in the gadodiamide group were significantly higher in the cerebellum (3.66 ± 0.91 nmol/g) compared with the gadoterate meglumine (0.26 ± 0.12 nmol/g; P < 0.05) and control (0.06 ± 0.10 nmol/g; P < 0.05) groups.Repeated administrations of the linear GBCA gadodiamide to healthy rats are associated with progressive and persistent T1 signal hyperintensity in the DCN, with Gd deposition in the cerebellum in contrast with the macrocyclic GBCA gadoterate meglumine for which no effect was observed.

View Article: PubMed Central - PubMed

Affiliation: From the *Guerbet Research and Innovation Department, Aulnay-sous-Bois; †Institut du Cerveau et de la Moelle Epinière (ICM), Centre de Neuroimagerie de Recherche (CENIR), Paris, France; Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, INSERM UMR-S1127, CNRS 7225, Paris; Service de Neuroradiologie, Hôpital de la Pitié-Salpêtrière, Paris, France; and ‡INSERM, U836, Grenoble, France; Université Grenoble Alpes, Grenoble Institute of Neurosciences, Grenoble, France.

ABSTRACT

Objectives: To prospectively compare in healthy rats the effect of multiple injections of macrocyclic (gadoterate meglumine) and linear (gadodiamide) gadolinium-based contrast agents (GBCAs) on T1-weighted signal intensity in the deep cerebellar nuclei (DCN), including the dentate nucleus.

Materials and methods: Healthy rats (n = 7/group) received 20 intravenous injections of 0.6 mmol of gadolinium (Gd) per kilogram (4 injections per week during 5 weeks) of gadodiamide, gadoterate meglumine, or hyperosmolar saline (control group). Brain T1-weighted magnetic resonance imaging was performed before and once a week during the 5 weeks of injections and during 5 additional weeks (treatment-free period). Gadolinium concentrations were measured with inductively coupled plasma mass spectrometry in plasma and brain. Blinded qualitative and quantitative evaluations of the T1 signal intensity in DCN were performed, as well as a statistical analysis on quantitative data.

Results: A significant and persistent T1 signal hyperintensity in DCN was observed only in gadodiamide-treated rats. The DCN-to-cerebellar cortex signal ratio was significantly increased from the 12th injection of gadodiamide (1.070 ± 0.024) compared to the gadoterate meglumine group (1.000 ± 0.033; P < 0.001) and control group (1.019 ± 0.022; P < 0.001) and did not significantly decrease during the treatment-free period. Total Gd concentrations in the gadodiamide group were significantly higher in the cerebellum (3.66 ± 0.91 nmol/g) compared with the gadoterate meglumine (0.26 ± 0.12 nmol/g; P < 0.05) and control (0.06 ± 0.10 nmol/g; P < 0.05) groups.

Conclusions: Repeated administrations of the linear GBCA gadodiamide to healthy rats are associated with progressive and persistent T1 signal hyperintensity in the DCN, with Gd deposition in the cerebellum in contrast with the macrocyclic GBCA gadoterate meglumine for which no effect was observed.

No MeSH data available.


Injection and MRI scheme. Four injections of 0.6 mmol of Gd per kilogram per week were performed for 5 weeks.
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Figure 1: Injection and MRI scheme. Four injections of 0.6 mmol of Gd per kilogram per week were performed for 5 weeks.

Mentions: T1-weighted MRI was performed under general anesthesia (3%–3.5% isoflurane) before the first GBCA administration and once a week during the treatment period (ie, after the fourth, eighth, 12th, 16th, and 20th injections) and for an additional 5-week treatment-free period (Fig. 1). During the administration period, MRI examination was performed 3 days after the last administration. Magnetic resonance imaging was performed with a dedicated quadrature brain coil (RAPID Biomedical GmbH, Rimpar, Germany) on a 2.35 T preclinical magnet (BioSpec 24/40, Bruker, Ettlingen, Germany) using a T1w-RARE sequence: repetition time/echo time, 525 milliseconds (ms)/10 ms, 36 averages; in plane resolution, 156 × 156 μm2; slice thickness, 800 μm; acquisition time, 15 minutes 8 seconds. The scan range of the MRI sequence covered the cerebellum only (10 slices). After the last MRI examination, all animals were sacrificed by exsanguination under anesthesia, and the brains were harvested for total Gd determination.


T1-Weighted Hypersignal in the Deep Cerebellar Nuclei After Repeated Administrations of Gadolinium-Based Contrast Agents in Healthy Rats: Difference Between Linear and Macrocyclic Agents.

Robert P, Lehericy S, Grand S, Violas X, Fretellier N, Idée JM, Ballet S, Corot C - Invest Radiol (2015)

Injection and MRI scheme. Four injections of 0.6 mmol of Gd per kilogram per week were performed for 5 weeks.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494686&req=5

Figure 1: Injection and MRI scheme. Four injections of 0.6 mmol of Gd per kilogram per week were performed for 5 weeks.
Mentions: T1-weighted MRI was performed under general anesthesia (3%–3.5% isoflurane) before the first GBCA administration and once a week during the treatment period (ie, after the fourth, eighth, 12th, 16th, and 20th injections) and for an additional 5-week treatment-free period (Fig. 1). During the administration period, MRI examination was performed 3 days after the last administration. Magnetic resonance imaging was performed with a dedicated quadrature brain coil (RAPID Biomedical GmbH, Rimpar, Germany) on a 2.35 T preclinical magnet (BioSpec 24/40, Bruker, Ettlingen, Germany) using a T1w-RARE sequence: repetition time/echo time, 525 milliseconds (ms)/10 ms, 36 averages; in plane resolution, 156 × 156 μm2; slice thickness, 800 μm; acquisition time, 15 minutes 8 seconds. The scan range of the MRI sequence covered the cerebellum only (10 slices). After the last MRI examination, all animals were sacrificed by exsanguination under anesthesia, and the brains were harvested for total Gd determination.

Bottom Line: The DCN-to-cerebellar cortex signal ratio was significantly increased from the 12th injection of gadodiamide (1.070 ± 0.024) compared to the gadoterate meglumine group (1.000 ± 0.033; P < 0.001) and control group (1.019 ± 0.022; P < 0.001) and did not significantly decrease during the treatment-free period.Total Gd concentrations in the gadodiamide group were significantly higher in the cerebellum (3.66 ± 0.91 nmol/g) compared with the gadoterate meglumine (0.26 ± 0.12 nmol/g; P < 0.05) and control (0.06 ± 0.10 nmol/g; P < 0.05) groups.Repeated administrations of the linear GBCA gadodiamide to healthy rats are associated with progressive and persistent T1 signal hyperintensity in the DCN, with Gd deposition in the cerebellum in contrast with the macrocyclic GBCA gadoterate meglumine for which no effect was observed.

View Article: PubMed Central - PubMed

Affiliation: From the *Guerbet Research and Innovation Department, Aulnay-sous-Bois; †Institut du Cerveau et de la Moelle Epinière (ICM), Centre de Neuroimagerie de Recherche (CENIR), Paris, France; Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, INSERM UMR-S1127, CNRS 7225, Paris; Service de Neuroradiologie, Hôpital de la Pitié-Salpêtrière, Paris, France; and ‡INSERM, U836, Grenoble, France; Université Grenoble Alpes, Grenoble Institute of Neurosciences, Grenoble, France.

ABSTRACT

Objectives: To prospectively compare in healthy rats the effect of multiple injections of macrocyclic (gadoterate meglumine) and linear (gadodiamide) gadolinium-based contrast agents (GBCAs) on T1-weighted signal intensity in the deep cerebellar nuclei (DCN), including the dentate nucleus.

Materials and methods: Healthy rats (n = 7/group) received 20 intravenous injections of 0.6 mmol of gadolinium (Gd) per kilogram (4 injections per week during 5 weeks) of gadodiamide, gadoterate meglumine, or hyperosmolar saline (control group). Brain T1-weighted magnetic resonance imaging was performed before and once a week during the 5 weeks of injections and during 5 additional weeks (treatment-free period). Gadolinium concentrations were measured with inductively coupled plasma mass spectrometry in plasma and brain. Blinded qualitative and quantitative evaluations of the T1 signal intensity in DCN were performed, as well as a statistical analysis on quantitative data.

Results: A significant and persistent T1 signal hyperintensity in DCN was observed only in gadodiamide-treated rats. The DCN-to-cerebellar cortex signal ratio was significantly increased from the 12th injection of gadodiamide (1.070 ± 0.024) compared to the gadoterate meglumine group (1.000 ± 0.033; P < 0.001) and control group (1.019 ± 0.022; P < 0.001) and did not significantly decrease during the treatment-free period. Total Gd concentrations in the gadodiamide group were significantly higher in the cerebellum (3.66 ± 0.91 nmol/g) compared with the gadoterate meglumine (0.26 ± 0.12 nmol/g; P < 0.05) and control (0.06 ± 0.10 nmol/g; P < 0.05) groups.

Conclusions: Repeated administrations of the linear GBCA gadodiamide to healthy rats are associated with progressive and persistent T1 signal hyperintensity in the DCN, with Gd deposition in the cerebellum in contrast with the macrocyclic GBCA gadoterate meglumine for which no effect was observed.

No MeSH data available.