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Objective:To explore the method of establishing a modified demyelination and myelination regeneration model induced by dicyclohexanone oxalyl dihydrazone (CPZ) in mice with multiple sclerosis (MS), and to analyze the image markers of demyelination and myelination regeneration in mouse MS model.Methods:After the intragastrically administered with sodium carboxymethyl cellulose (CMCNa) for one week, a total of 30 C57BL/6 male mice were randomly divided into the control group ( n=10), the demyelination group ( n=10), and the remyelination group ( n=10). The mice of the control group were immediately performed MR scanning and pathological specimen obtaining; the mice in the demyelination group were administered with intragastrical CPZ-CMCNa once a day for 6 weeks for inducing demyelination, then received MR scanning and specimen obtaining with the same protocols used in control group; the mice in the remyelination group were administered with intragastrical CPZ-CMCNa once a day for six weeks for demyelination, then CPZ was withdrawn and normal diet was given for another four weeks. Then MR scanning and specimen obtaining were performed with the same protocols used in the other two groups. Regions of interest (ROIs) were set at the rostrum of corpus callosum (rCC), the bilateral normal appearing white matters (NAWM) of the rostrum of corpus callosum, and the bilateral cerebral cortex (Cx). The normalized T 2WI (T 2-normalized), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were compared among the three groups by one-way ANOVA. Results:The demyelination and remyelination mice model of MS were successfully established. The T 2-normalized values of rCC in control group, demyelination group and remyelination group were 0.47±0.03, 0.72±0.04, 0.54±0.04, respectively, with statistically significant difference found ( F=90.511, P<0.05). Post-hoc multiple comparisons showed significant differences among those groups ( P<0.05). There was no significant difference of T 2-normalized value in NAWM and Cx among the three groups ( P>0.05). Moreover, there were significant differences in the FA values (0.36±0.04, 0.29±0.03, and 0.32±0.05), the MD values [(0.572±0.015), (0.598±0.034), and (0.626±0.043)×10 -3 mm 2/s], the AD values [(0.79±0.04), (0.77±0.06), and (0.83±0.04)×10 -3 mm 2/s], and the RD values [(0.46±0.02), (0.51±0.03), and (0.53±0.05)×10 -3 mm 2/s] of rCC of the control group, the demyelination group, and the remyelination group (all P<0.05). Significant difference was found in FA values between the demyelination group and the control group ( P<0.05), and in MD values between the remyelination group and the control group ( P<0.05), as well as in AD values between the remyelination group and the demyelination group ( P<0.05). There were also significant differences in RD values between the remyelination group and the control group, and the demyelination group and the control group (all P<0.05). However, no significant difference was found in all diffusion tensor imaging (DTI) metrics of NAWM and Cx among the three groups (all P>0.05). The LFB-eosin staining showed that the myelin sheath of rCC was lost in the demyelination group, and the rCC was partially regenerated and repaired in the remyelination group. Conclusion:The modified CPZ-CMCNa model can selectively induce demyelination and remyelination of rCC, and the changes of demyelination and remyelination of rCC in the modified CPZ-CMCNa model can be quantitatively detected by T 2WI combined with DTI, which might provide related theoretical basis for the study on dynamic changes of MS lesions.
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Objective To assess the changes of white matter microstructure in neuromyelitis optica spectrum disorders (NMOSD) with DTI based on tract-based spatial statistics (TBSS) method.Methods Conventional MR and DTI were performed in 20 NMOSD patients (NMOSD group) and 20 healthy volunteers (control group).DTI data were analyzed with TBSS procedure,which was a part of FSL software packages,and non-parametric statistical analysis was performed on the whole brain.Correlation between FA value of tracts with significant difference in NMOSD group and expanded disability status scale (EDSS) scores was analyzed.Results TBSS analysis revealed significantly (P＜ 0.05,FWE corrected) extensive decrease of FA value in cerebrum and cerebellum white matter fiber bundles,i.e.corpus callosum,fornix,corticospinal tract,unciform fasciculus,cerebellar peduncles etc.in NMOSD group,and decrease of AD value,increase of RD value in cingulum bundle,corpus callosum and fornix,while MD value only increased in fornix and retrolenticular part of the left internal capsule (P＜0.05,FWE corrected).Negative correlations were found between FA value of left uncinate fasciculus,right external capsule,left inferior cerebellar peduncle,bilateral anterior limb of internal capsule,medial lemniscus and EDSS scores (all P＜0.05).Conclusion Widespread white matter damage is observed in cerebrum and cerebellum in NMOSD patients by using TBSS analysis,which may partly correspond to the disabilities of NMOSD patients.However,the other microstructural changes of white matter tracts may suggest complicated pathological mechanism of NMOSD.
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Objective To assess the damage of limbic system pathways in relapsing-remitting multiple sclerosis (RRMS) by diffusion tensor imaging (DTI) tractography.Methods DTI tractography was used to acquire fiber numbers,fractional anisotropy (FA),mean diffusivity (MD) of cingulum,fornix,and uncinate fasciculus (UF) in 20 RRMS patients (MS group) and 20 healthy volunteers (control group),and statistical analysis was performed.Results Compared with control group,lower FA value (P＜0.01) and higher MD value (P＜0.05) were found in cingulum,fornix and UF of MS group,and the fiber numbers of fornix decreased in MS group (P＜0.001).There were significant differences between the left and the right UF in fiber numbers and FA value of control group and the fiber numbers of MS group.Negative correlations were found between FA value of cingulum and UF and EDSS scores in MS group (r=-0.572,-0.665,both P＜0.05),and positive correlations were found between MD value and EDSS scores (r=0.627,0.603,both P＜0.05).Conclusion DTI tractography is valuable in assessing MS associated limbic system damage and in monitoring the clinical progression of the disease.