Limits...
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.


Related in: MedlinePlus

Evolution of DCN/cerebellar parenchyma and DCN/brain stem T1w signal ratio, over the course of the injections (mean ± SD). Statistical comparisons are described in the Results section.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5383202&req=5

Figure 7: Evolution of DCN/cerebellar parenchyma and DCN/brain stem T1w signal ratio, over the course of the injections (mean ± SD). Statistical comparisons are described in the Results section.

Mentions: Quantitatively, no significant T1 signal changes were observed in both saline groups. In the gadodiamide-treated groups, a significant increase in the DCN-brain stem T1 signal ratio was shown after 3 weeks of injections in the gadodiamide sham group (W1 vs W4 to W6: P < 0.001; W2 vs W5 and W6: P < 0.001; W3 vs W5 and W6: P < 0.05) and after only 2 weeks of injections (ie, 1 week earlier) in the gadodiamide + SNx group (W1 vs W3 to W6: P < 0.001; W2 vs W3: P < 0.05; W2 vs W4 to W6: P < 0.001) (Fig. 7A). A similar effect was seen with the DCN/cerebellar parenchyma ratio (Fig. 7B) for the gadodiamide sham group from 3 weeks of injections, and for the gadodiamide + SNx group, leading to a higher ratio for this group compared with the other groups from 2 weeks of injections (because no significant effect was found for the interaction group × week, no further statistical tests were performed). Therefore, renal failure was associated with an earlier and greater increase in both ratios after gadodiamide administration.


Moderate Renal Failure Accentuates T1 Signal Enhancement in the Deep Cerebellar Nuclei of Gadodiamide-Treated Rats
Evolution of DCN/cerebellar parenchyma and DCN/brain stem T1w signal ratio, over the course of the injections (mean ± SD). Statistical comparisons are described in the Results section.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5383202&req=5

Figure 7: Evolution of DCN/cerebellar parenchyma and DCN/brain stem T1w signal ratio, over the course of the injections (mean ± SD). Statistical comparisons are described in the Results section.
Mentions: Quantitatively, no significant T1 signal changes were observed in both saline groups. In the gadodiamide-treated groups, a significant increase in the DCN-brain stem T1 signal ratio was shown after 3 weeks of injections in the gadodiamide sham group (W1 vs W4 to W6: P < 0.001; W2 vs W5 and W6: P < 0.001; W3 vs W5 and W6: P < 0.05) and after only 2 weeks of injections (ie, 1 week earlier) in the gadodiamide + SNx group (W1 vs W3 to W6: P < 0.001; W2 vs W3: P < 0.05; W2 vs W4 to W6: P < 0.001) (Fig. 7A). A similar effect was seen with the DCN/cerebellar parenchyma ratio (Fig. 7B) for the gadodiamide sham group from 3 weeks of injections, and for the gadodiamide + SNx group, leading to a higher ratio for this group compared with the other groups from 2 weeks of injections (because no significant effect was found for the interaction group × week, no further statistical tests were performed). Therefore, renal failure was associated with an earlier and greater increase in both ratios after gadodiamide administration.

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.


Related in: MedlinePlus