Limits...
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 qualitative blinded evaluation of the T1w signal hyperintensity between DCN area and cerebellar cortex (mean ± SD).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4494686&req=5

Figure 7: Temporal changes in qualitative blinded evaluation of the T1w signal hyperintensity between DCN area and cerebellar cortex (mean ± SD).

Mentions: Figures 3 (gadodiamide), 4 (gadoterate meglumine), and 5 (control) show typical examples of brain MRI during both the injection and the treatment-free periods. Figure 6 displays DCN T1w MR images of all animals on completion of the 10-week study period. Qualitatively, after a randomized reading of the 200 images (20 rats × 10 weeks follow-up) by the 2 blinded neuroradiologists, increase in signal intensity was detected only in the gadodiamide group by both readers (Fig. 7). A good agreement was observed between the 2 readers. No reader effect was demonstrated by the 2 blinded neuroradiologists (P = 0.1). Compared to the preinjection DCN/cerebellar cortex ratio, a marked difference was progressively observed between gadodiamide and gadoterate meglumine or hyperosmolar saline during the injection period. The T1 signal hyperintensity in the DCN remained stable during the treatment-free period and was qualitatively equivalent between the end of the treatment period (ie, at 5 weeks) and at completion of the treatment-free period (ie, at 10 weeks) in the gadodiamide group. No difference was detected between gadoterate meglumine and control at any time point. No statistical results are presented owing to the poor convergence of the multinomial model (insufficient number of degrees of freedom due to the repeated data).


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 qualitative blinded evaluation of the T1w signal hyperintensity between DCN area and cerebellar cortex (mean ± SD).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 7: Temporal changes in qualitative blinded evaluation of the T1w signal hyperintensity between DCN area and cerebellar cortex (mean ± SD).
Mentions: Figures 3 (gadodiamide), 4 (gadoterate meglumine), and 5 (control) show typical examples of brain MRI during both the injection and the treatment-free periods. Figure 6 displays DCN T1w MR images of all animals on completion of the 10-week study period. Qualitatively, after a randomized reading of the 200 images (20 rats × 10 weeks follow-up) by the 2 blinded neuroradiologists, increase in signal intensity was detected only in the gadodiamide group by both readers (Fig. 7). A good agreement was observed between the 2 readers. No reader effect was demonstrated by the 2 blinded neuroradiologists (P = 0.1). Compared to the preinjection DCN/cerebellar cortex ratio, a marked difference was progressively observed between gadodiamide and gadoterate meglumine or hyperosmolar saline during the injection period. The T1 signal hyperintensity in the DCN remained stable during the treatment-free period and was qualitatively equivalent between the end of the treatment period (ie, at 5 weeks) and at completion of the treatment-free period (ie, at 10 weeks) in the gadodiamide group. No difference was detected between gadoterate meglumine and control at any time point. No statistical results are presented owing to the poor convergence of the multinomial model (insufficient number of degrees of freedom due to the repeated data).

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