Study On The Multimodal Magnetic Resonance Imaging Of Subcortical Ischemic Vascular Disease And The Relationships With Cognitive Impairment

PART I MRI STUDY OF WHITE MATTER LESIONS AND THE RELATIONSHIPS WITH COGNITIVE IMPAIRMENT IN PATIENTS WITH SUBCORTICAL ISCHEMIC VASCULAR DISEASEObjective: To investigate the characters of white matter hyperintensity(WMH)as well as the alterations of microstructures of the neural fibers and the relationships with cognitive impairment in patients with subcortical ischemic vascular disease(SIVD).Methods: Twenty-five SIVD patients with cognitive impairment(SVCI = 25),25 SIVD patients with normal cognitive function(pre-SVCI= 25),and 23 normal control volunteers(NC = 23)matched by sex,age and educational years were selected.All the subjects underwent clinical history acquisition,blood biochemical examination,cognitive neuropsychological scale evaluation and multimodal MRI sequence scanning,including the high-resolution 3D-T1 WI sequence and diffusion tensor imaging(DTI).Then the following data were analyzed and processed:(1)Qualitative analysis and quantitative analysis were used to evaluate the visual score of WMH and calculate the intracerebral volume(ICV),white matter volume(WMV)and WMH volume,and to compare the differences between and within groups and their relationships with cognitive impairment;(2)TBSS analysis was used to calculate the fractional anisotropy(FA),the mean diffusivity(MD),the axial diffusivity(AD)and the radial diffusivity(RD).These parameters were used to evaluate the changes of white matter skeleton and their correlations with cognitive impairment.Results: With the progress of the disease,the WMV decreased,the WMH volume increased,the WMH visual score and lacunar visual count increased as well.The difference was statistically significant(P<0.05).The WMH volume in SVCI group was positively correlated with the reaction times of the stroop color-word test I(r=0.52,P=0.008).There was a significant correlation between qualitative and quantitative analysis of WMH.TBSS analysis showed that the extensive damage of white matter fibers had occurred in the precursor stage of disease(pre-SVCI group),and the distribution of white matter lesions were similar to that of SVCI group,but relatively limited.The most injured white matter fibers were the genu of corpus callosum,bilateral inferior fronto-occipital fasciculus tract,bilateral superior longitudinal tract,bilateral inferior longitudinal tract,bilateral anterior thalamic radiation and corticospinal tract.DTI parameters showed the FA value decreased,the MD,AD and RD value increased,and the knee of corpus callosum was treated as the most damaged fibrous bundle.The mean values of the FA and MD of the right inferior longitudinal bundle in pre-SVCI group were positively correlated with reverse digital span test(r=0.44,P=0.04),and trail making test B(r=0.45,P=0.03).The mean AD values of right superior longitudinal bundle were positively correlated with stroop color-word test II(r=0.52,P=0.01),the RD values of left inferior longitudinal bundle were positively correlated with the trail making test B(r=0.43,P=0.04)Conclusion: SIVD patients have extensive white matter lesions,which aggravate with the progress of the disease.The WMH volume and the destruction of the microstructures of neural fibers are related to cognitive impairment.PART II MRI STUDY OF CHANGED BRAIN STRUCTURE AND FUNCTIONAL CONNECTIVITY IN PATIENTS WITH SUBCORTICAL ISCHEMIC VASCULAR DISEASE AND THE CORRELATIONS WITH COGNITIVE IMPAIREMRNTObjective: To explore the changes of gray matter structure and brain functional connectivity in patients with subcortical ischemic vascular disease(SIVD)and their relationships with cognitive impairment.To further reveal the neuropathological mechanism of cognitive dysfunction.Methods: The subjects were the same as the part I.All of the subjects underwent clinical history acquisition,blood biochemical examination,cognitive neuropsychological scale evaluation and multimodal MRI sequence scanning,including the high-resolution 3D-T1 WI sequence and resting-state fMRI sequence scanning.Then the following data analysis and processing are carried out:(1)The structure and function data preprocessing uses MRIcorn software,SPM8 and DPABI software based on MATLAB platform.(2)The intracerebral volume,white matter volume and gray matter volume of subjects were calculated by VBM8 software based on SPM.The gray matter volume between groups and within groups was compared with age,sex,education years and intracranial volume as covariables.Family-wise error rate(FWE)based on voxel level was used for multiple comparisons.The significance of the test was statistically significant(P < 0.05).(3)The potential relationship between gray matter volume and neuropsychological scale score was analyzed by partial correlation method.(4)Using the brain regions with significantly changedgray matter volumes as seeds,DPABI and REST software were used to analyze the whole brain functional connectivity based on the seeds,and the differences of functional connectivity between groups and within groups were compared.Multiple comparisons were made with cluster-level of FWE.The significance of the test was statistically significant at P < 0.05.(5)The mean values of brain regions with statistical changed functional connectivity were extracted,and the potential relationships between functional connectivity and neuropsychological scale score was analyzed by partial correlation method with age,gender and education years as covariates.Results: There were significant differences among the three groups in the right inferior frontal gyrus,right gyrus rectus,left inferior frontal gyrus,right olfactory cortex,left middle temporal gyrus,right insula,right thalamus and bilateral caudate nucleus(P < 0.05,FWE corrected).Compared with NC group,the volume of gray matter decreased in the right inferior orbital frontal gyrus and increased in the bilateral caudate nucleus in the pre-SVCI group.The volume of gray matter in SVCI group decreased in the right inferior orbital frontal gyrus,right gyrus rectus,left inferior frontal gyrus,right olfactory cortex,left middle temporal gyrus,right cerebral island,right thalamus and increased in the bilateral caudate nucleus compared with the NC group.In SVCI group,the right insular gray matter volume was negatively correlated with stroop color-word test II(r=-0.58,P=0.005).The left inferior frontal gyrus gray matter volume was negatively correlated with stroop color-word test II(r=-0.63,P=0.002).The results of functional connectivity analysis based on gray matter structure showed that abnormal functional connectivity existed between left caudate nucleus and left supplementary motor area,right insula and bilateral posterior central gyrus,right superior temporal gyrus and left cingulategyrus,left superior temporal gyrus and right superior temporal gyrus,bilateral posterior central gyrus and left median cingulate and paracingulate gyri(P < 0.05,cluster-level FWE corrected).Compared with the pre-SVCI group,the SVCI group had lower functional connectivity between left caudate nucleus and left supplementary motor area,right insula and left posterior central gyrus.Compared with the NC group,the SVCI group had abnormal functional connectivity of multiple brain regions,and the distributions was the same as that among the three groups.The functional connectivity between left superior temporal gyrus and right superior temporal gyrus in SVCI group was negatively correlated with trail making test B(r=-0.63,P=0.002);the functional connectivity between right insula and left median cingulate and paracingulate gyri in SVCI group was negatively correlated with trail making test B test(r=-0.61,P=0.003).Conclusion: There are decreased gray matter volume and abnormal functional connectivity in multiple brain regions in patients with SIVD,and these alterations are closely related to the cognitive impairment.PART III MRI STUDY OF ALTERED COUPLING BETWEEN THE PERFUSION AND FUNCTIONAL CONNECTIVITY IN PATIENTS WITH SUBCORTICAL ISCHEMIC VASCULAR DISEASE AND THE CORRELATIONS WITH COGNITIVE IMPAIREMRNTObjective: To study the coupling changes of cerebral blood flow and functional connectivity in patients with SIVD and their relationship with cognitive impairment.Methods: 28 SIVD patients with cognitive impairment(SVCI = 28),26 SIVD patients with normal cognitive(pre-SVCI = 25),and 24 normal control volunteers(NC=24)matched by sex,age and educational years were selected.All subjects underwent clinical history acquisition,blood biochemical examination,cognitive neuropsychological scale assessment and multimodal MRI scanning,including three-dimensional pseudo-continuous arterial spin labeling(3D-pCASL)and resting state functional magnetic resonance(rs-fMRI)sequences.Then the following data analysis and processing are carried out:(1)the rs-fMRI data preprocessing is consistent with the second part,then the Reho value is calculated by REST software,and so as the CoHeReho coefficient.Finally,Fisher Z transformation was carried out to obtain the Reho statistical maps.(2)3D-pCASL data was preprocessed by GE ADW4.5 workstation to get CBF map and then using MRIcorn and SPM8 software to process data format conversion,standardization,normalization and smoothing,and finally get the rCBF statistical maps.(3)Coupling analysis: DPABI software was used to calculate the cross-voxel correlation analysis andReho/rCFB ratio coupling.The differences between groups and within groups were compared.The threshold of monomer was P<0.001.The cluster level FWE multiple correction was used.(4)Correlation analysis was made between the statistically significant ratio coupling results and cognitive neuropsychological scores.Results: Reho/rCBF ratio coupling had abnormalities in multiply brain regions,including the left insula,the right middle temporal gyrus,the right precuneus,the left anterior central gyrus and the left inferior frontal gyrus(P < 0.05,cluster level FWE corrected).Intra-group analysis showed that the Reho/rCBF ratio decreased and inverted abnormally in the patient group.The left insular lobe,the right anterior cuneiform lobe and the left inferior frontal gyrus were significantly difference between each pair of the groups.The group level results of the Reho-rCBF cross-voxel coupling showed that with the development of disease,the Reho-rCBF coupling correlation decreased gradually.Individual level results showed that,the Reho-rCBF voxel coupling in SIVD patients gradually changed from positive correlation to negative correlation compared with normal volunteers.The coupling value of Reho/rCBF ratio in left anterior central gyrus was positively correlated with MMSE(r=0.63,P=0.002).Conclusion: SIVD patients have coordination impairment of cerebral perfusion and functional connectivity,which is related to cognitive impairment.