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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.


Related in: MedlinePlus

Temporal changes in DCN/cerebellar cortex T1w signal ratio (mean ± SD).
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Figure 8: Temporal changes in DCN/cerebellar cortex T1w signal ratio (mean ± SD).

Mentions: Quantitatively, no differences were observed between the 3 groups before any injection (P = 0.5). However, a significant increase in the DCN/cerebellar cortex ratio was observed only in the gadodiamide-treated group from the 12th injection compared to both gadoterate meglumine and control groups: 1.070 ± 0.024 vs 1.000 ± 0.033 (P < 0.001) and 1.019 ± 0.022 (P < 0.001), respectively (Fig. 8). This increase was dose dependent throughout the injection period (positive linearity test, P < 0.0001). All rats that received gadodiamide had an increase in the DCN/cerebellar cortex ratio. The maximum value was reached for each rat from the 12th to the 20th injection of gadodiamide. This DCN/cerebellar cortex ratio persisted at completion of the treatment-free period and did not significantly decrease during the 5-week period after the last injection (P = 0.1). No difference was observed between gadoterate meglumine and control groups at any time point. However, a slight but significant linear decrease was observed for the gadoterate meglumine group and the control group from week 1 to week 10 (positive linearity test, P < 0.0001).


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)

Temporal changes in DCN/cerebellar cortex T1w signal ratio (mean ± SD).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 8: Temporal changes in DCN/cerebellar cortex T1w signal ratio (mean ± SD).
Mentions: Quantitatively, no differences were observed between the 3 groups before any injection (P = 0.5). However, a significant increase in the DCN/cerebellar cortex ratio was observed only in the gadodiamide-treated group from the 12th injection compared to both gadoterate meglumine and control groups: 1.070 ± 0.024 vs 1.000 ± 0.033 (P < 0.001) and 1.019 ± 0.022 (P < 0.001), respectively (Fig. 8). This increase was dose dependent throughout the injection period (positive linearity test, P < 0.0001). All rats that received gadodiamide had an increase in the DCN/cerebellar cortex ratio. The maximum value was reached for each rat from the 12th to the 20th injection of gadodiamide. This DCN/cerebellar cortex ratio persisted at completion of the treatment-free period and did not significantly decrease during the 5-week period after the last injection (P = 0.1). No difference was observed between gadoterate meglumine and control groups at any time point. However, a slight but significant linear decrease was observed for the gadoterate meglumine group and the control group from week 1 to week 10 (positive linearity test, P < 0.0001).

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.


Related in: MedlinePlus