Synopsis

Altered brain structure in cirrhotic patients have been seen in previously reported studies. Many studies focus on the grey matter change of the caudate putamen, while few study investigate the relationship of thalamus grey matter change and cirrhotic symptoms. Our study reveal that the grey matter density of thalamus is closely correlated with the clinical makers of the cirrhosis, which may help to clarify the mechanism of the thalamus structural change.

Purpose

Methods

45 cirrhotic patients without MHE ( age = 49.8 ± 8.97, No-HE group ), 33 cirrhotic patients with current MHE ( age = 51.7 ± 8.43, MHE group ) and 21 healthy controls ( age = 51.5 ± 7.67, Control group ) were enrolled in the study. Total bilirubin levels, albumin levels, ALT levels, AST levels, ratio of AST and ALT, blood coagulation time and Child-Pugh Score were collected from 54 of the cirrhotic patients ( 21 in MHE group, 33 in No-HE group ). Neuropsychological tests including Number Connection Test A, Number Connection Test B, Digit Symbol Test and Block Design Test were used to evaluate the cognitive state of all the subjects.

MR imaging data were acquired with a 3.0 T Siemens MRI scanner. The DARTEL method in SPM8 package were used to do segmentation and normalization of the 3d T1 images. Smoothed grey matter density images of the three groups were analyzed with an ANOVA test to detect brain regions of significant grey matter density difference. Multiple comparison correction were performed by using family wise error rate correction with a cluster defining threshold P=0.001 ( two tail ), corresponding to a cluster level of P=0.05. Post-hoc t tests with bonferroni correction were used to compare the intergroup difference within the mask of the ANOVA results.

The grey matter density of brain regions of significant difference in ANOVA test were extracted and compared among groups. Within group Pearson correlations were performed between the regional grey matter density and clinical markers, and also with the performance of the neuropsychological tests. Multiple correlation correction were performed with a false discovery rate ( FDR ) correction.

Results

Decreased grey matter density are found in bilateral striatum, left hippocampus, cerebellar vermis and most notably in putamen when the cirrhotic patients are compared to the healthy controls, while the bilateral thalamus and the calcarine cortex exhibit significant increased grey matter density( Fig1, Fig2 ). The grey matter change of the thalamus ranks the highest difference level of the ANOVA analysis.

The grey matter density of the thalamus correlates with the Child-Pugh Score in MHE group ( r= 0.632, P = 0.002, Q = 0.046, Fig 3. ), and it correlates with AST/ALT in both the No-HE group ( r = 0.497, P = 0.003, Q = 0.048, Fig 4. ) and MHE group( r = 0.657, P = 0.001, Q = 0.046 ). The grey matter density of the thalamus also correlates with blood coagulation time ( r = 0.633, P = 0.001, Q = 0.003 ) and negatively correlates with albumin levels ( r = -0.555, P = 0.001, Q = 0.017) in No-HE group. In MHE group, thalamus grey matter density still has a certain degree of correlation with the blood coagulation time ( r = 0.578, P = 0.006, Q = 0.088 ) and albumin levels ( r = -0.448, P = 0.042, Q = 0.36 ), but do not pass the FDR correction. There is no correlation between thalamus grey matter density and the neuropsychological tests performance, and there also do not exist a correlation between grey matter density of other brain regions and clinical makers or neuropsychological tests performance.

Discussion

Conclusion

Acknowledgements

References

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