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Moderate Renal Failure Accentuates T1 Signal Enhancement in the Deep Cerebellar Nuclei of Gadodiamide-Treated Rats

View Article: PubMed Central - PubMed

ABSTRACT

Objectives: The purpose of this preclinical study was to investigate whether moderate chronic kidney disease is a factor in potentiating gadolinium (Gd) uptake in the brain.

Materials and methods: A comparative study was performed on renally impaired (subtotal nephrectomy) rats versus rats with normal renal function. The animals received 4 daily injections of 0.6 mmol Gd/kg a week for 5 weeks (cumulative dose of 12 mmol Gd/kg) of gadodiamide or saline solution. The MR signal enhancement in the deep cerebellar nuclei was monitored by weekly magnetic resonance imaging examinations. One week after the final injection, the total Gd concentration was determined by inductively coupled plasma mass spectrometry in different regions of the brain including the cerebellum, plasma, cerebrospinal fluid, parietal bone, and femur.

Results: After the administration of gadodiamide, the subtotal nephrectomy group presented a significantly higher T1 signal enhancement in the deep cerebellar nuclei and a major increase in the total Gd concentration in all the studied structures, compared with the normal renal function group receiving the same linear Gd-based contrast agent. Those potentiated animals also showed a pronounced hypersignal in the choroid plexus, still persistent 6 days after the last injection, whereas low concentration of Gd was found in the cerebrospinal fluid (<0.05 μmol/L) at this time point. Plasma Gd concentration was then around 1 μmol/L. Interestingly, plasma Gd was predominantly in a dissociated and soluble form (around 90% of total Gd). Total Gd concentrations in the brain, cerebellum, plasma, and bones correlated with creatinine clearance in both the gadodiamide-treated groups.

Conclusions: Renal insufficiency in rats potentiates Gd uptake in the cerebellum, brain, and bones.

No MeSH data available.


Change in the choroid plexus/cerebellar parenchyma signal ratio and choroid plexus/brain stem signal ratio between week 1 and week 6 for gadodiamide sham (n = 10) and gadodiamide + SNx (n = 9) rats (mean + SD).
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Figure 6: Change in the choroid plexus/cerebellar parenchyma signal ratio and choroid plexus/brain stem signal ratio between week 1 and week 6 for gadodiamide sham (n = 10) and gadodiamide + SNx (n = 9) rats (mean + SD).

Mentions: Eight of 9 animals from the gadodiamide + SNx group presented T1-enhancement in the fourth ventricle and the CP, occurring from 2 weeks of injections. Typical images of this specific enhancement are shown in Figure 5. The CP-brain stem and CP-cerebellar parenchyma ratios calculated at week 1 and 6 (ie, before and after the treatment period) for the gadodiamide + SNx and gadodiamide sham groups are presented in Figure 6. While before injection of gadodiamide, the CP-brain stem ratio was 0.82 ± 0.10 in SNx rats versus 0.84 ± 0.05 in sham rats (NS), this ratio increased after the injection period (P < 0.05 for the gadodiamide sham group, P < 0.001 for the gadodiamide + SNx rats). However, CP enhancement was significantly higher in SNx rats compared with sham rats after gadodiamide injections (ratio of 1.13 ± 0.10 vs 0.92 ± 0.06, P < 0.001). A similar observation was made in the CP-cerebellar parenchyma ratio, although there was no significant increase between week 1 and week 6 in sham rats (0.93 ± 0.05 vs 0.99 ± 0.06 [NS], compared with 0.91 ± 0.10 versus 1.25 ± 0.12 in SNx rats [P < 0.001]).


Moderate Renal Failure Accentuates T1 Signal Enhancement in the Deep Cerebellar Nuclei of Gadodiamide-Treated Rats
Change in the choroid plexus/cerebellar parenchyma signal ratio and choroid plexus/brain stem signal ratio between week 1 and week 6 for gadodiamide sham (n = 10) and gadodiamide + SNx (n = 9) rats (mean + SD).
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Related In: Results  -  Collection

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Figure 6: Change in the choroid plexus/cerebellar parenchyma signal ratio and choroid plexus/brain stem signal ratio between week 1 and week 6 for gadodiamide sham (n = 10) and gadodiamide + SNx (n = 9) rats (mean + SD).
Mentions: Eight of 9 animals from the gadodiamide + SNx group presented T1-enhancement in the fourth ventricle and the CP, occurring from 2 weeks of injections. Typical images of this specific enhancement are shown in Figure 5. The CP-brain stem and CP-cerebellar parenchyma ratios calculated at week 1 and 6 (ie, before and after the treatment period) for the gadodiamide + SNx and gadodiamide sham groups are presented in Figure 6. While before injection of gadodiamide, the CP-brain stem ratio was 0.82 ± 0.10 in SNx rats versus 0.84 ± 0.05 in sham rats (NS), this ratio increased after the injection period (P < 0.05 for the gadodiamide sham group, P < 0.001 for the gadodiamide + SNx rats). However, CP enhancement was significantly higher in SNx rats compared with sham rats after gadodiamide injections (ratio of 1.13 ± 0.10 vs 0.92 ± 0.06, P < 0.001). A similar observation was made in the CP-cerebellar parenchyma ratio, although there was no significant increase between week 1 and week 6 in sham rats (0.93 ± 0.05 vs 0.99 ± 0.06 [NS], compared with 0.91 ± 0.10 versus 1.25 ± 0.12 in SNx rats [P < 0.001]).

View Article: PubMed Central - PubMed

ABSTRACT

Objectives: The purpose of this preclinical study was to investigate whether moderate chronic kidney disease is a factor in potentiating gadolinium (Gd) uptake in the brain.

Materials and methods: A comparative study was performed on renally impaired (subtotal nephrectomy) rats versus rats with normal renal function. The animals received 4 daily injections of 0.6 mmol Gd/kg a week for 5 weeks (cumulative dose of 12 mmol Gd/kg) of gadodiamide or saline solution. The MR signal enhancement in the deep cerebellar nuclei was monitored by weekly magnetic resonance imaging examinations. One week after the final injection, the total Gd concentration was determined by inductively coupled plasma mass spectrometry in different regions of the brain including the cerebellum, plasma, cerebrospinal fluid, parietal bone, and femur.

Results: After the administration of gadodiamide, the subtotal nephrectomy group presented a significantly higher T1 signal enhancement in the deep cerebellar nuclei and a major increase in the total Gd concentration in all the studied structures, compared with the normal renal function group receiving the same linear Gd-based contrast agent. Those potentiated animals also showed a pronounced hypersignal in the choroid plexus, still persistent 6 days after the last injection, whereas low concentration of Gd was found in the cerebrospinal fluid (&lt;0.05 &mu;mol/L) at this time point. Plasma Gd concentration was then around 1 &mu;mol/L. Interestingly, plasma Gd was predominantly in a dissociated and soluble form (around 90% of total Gd). Total Gd concentrations in the brain, cerebellum, plasma, and bones correlated with creatinine clearance in both the gadodiamide-treated groups.

Conclusions: Renal insufficiency in rats potentiates Gd uptake in the cerebellum, brain, and bones.

No MeSH data available.