Correlation Between White Matter Microstructural Lesions By Diffusion Tensor Imaging And Cognitive Disfunction In Obstructive Sleep Apnea-hypopnea Syndrome

In the recent years,the neurologist paid more attention to obstructive sleep apnea-hypopnea syndrome(OSAHS),which proved to be correlative with ischemic stroke.Some studies showed that the patients with OSAHS had cognitive deficit. However,there was few evidences for white matter microstructural lesions in OSAHS. In this study,we try to determine whether OSAHS has white matter microstructural lesions by MR diffusion tensor imaging(DTI),where they are,and whether they correlate with cognitive disfunction.Also,we will detect microstructural lesions in normal-appearing white matter(NAWM) both in patients with lacunar infarction(LI) and in patients with multiple sclerosis(MS).This thesis consists of four parts:the features of brain microstructure in healthy adults,the correlation between white matter microstructural lesions and cognitive disfunction in patients with OSAHS,microstructural lesions in NAWM in patients with LI,and microstructural lesions in NAWM in patients with relapsing-remitting MS.Chapter 1 The features of brain microstructure in healthy adults by DTIOBJECTIVES:To investigate the features of brain microstructure in healthy adults by DTI.METHODS:Fractional anisotropy(FA) and apparent diffusion coefficient(ADC) values was examined in regions of interest(ROI) respectively,and then diffusion tensor tractography(DTT) of corpus callosum was operated.The datas were dealed with SPSS 13.0,and numeric variables were represented by mean±standard deviation ((?)±SD).Paired-samples t test was applied when comparing paired samples.As usual,it was thought to have statistical significance when P<0.05.RESULTS:No significant differences were found in FA values in each ROI from bilateral brain(P>0.05).So was ADC values(P>0.05).Compared with gray matter including parahippocampal gyrus and anterior cingulate gyrus,white matter had higher FA values,such as white matter of left frontal lobe,corpus callosum,anterior cingulum and so on.According to FA values,ROI was sequenced one by one.The highest was splenium of corpus callosum,following genu of corpus callosum,trunk of corpus callosum,right posterior limb of internal capsule,left posterior limb of internal capsule,left genu of internal capsule,right genu of internal capsule,right optic radiation,left centrum semiovale,left optic radiation,right centrum semiovale,right anterior limb of internal capsule,left anterior limb of internal capsule,left anterior cingulum,right anterior cingulum,peripheric white matter of right anterior angle,right external capsule,peripheric white matter of left anterior angle,left external capsule, white matter of left frontal lobe,white matter of right frontal lobe,peripheric white matter of right posterior angle,peripheric white matter of left posterior angle,right thalamus,left thalamus,right anterior cingulate gyrus,right parahippocampal gyrus, left head of caudate nucleus,left parahippocampal gyrus,left anterior cingulate gyrus, and the lowest was right head of caudate nucleus.CONCLUSIONS:Firstly,no significant differences were found in FA values in bilateral brain,which indicated that the density of white matter fibers were also unanimous.Secondly,Anisotropy varied in each brain structure,generally white matter had remarkable higher anisotropy compared with gray matter.Finally,there was different anisotropy in three types nerve fibres:commissural fibers had the highest anisotropy,the following were projection fibers,and internuncial fibers were the lowest.Chapter 2 The relationship between white matter microstructural lesions by DTI and cognitive disfunction in patients with OSAHSOBJECTIVES:To investigate whether OSAHS has white matter microstructural lesions and unstuck sleep architecture,where are white matter microstructural lesions by DTI,and whether white matter microstructural lesions or unstuck sleep architecture correlate with cognitive disfunction.METHODS:FA and ADC values was examined in ROI respectively,and then DTT of corpus callosum was operated.Moreover,MMSE and WMS values were recorded respectively before polysomnogram(PSG) was detected.The datas were dealed with SPSS 13.0,and numeric variables were represented by mean±standard deviation((?)+SD.Independent-samples t test was applied when comparing OSAHS group with controls.Also,partial correlations was adopted.As usual,it was thought to have statistical significance when P＜0.05.RESULTS:Compared with control group,significant lower FA values were found in multiple regions as below in patients in OSAHS:white matter of right frontal lobe(t＝2.367,P＝0.029),splenium of corpus callosum(t＝2.118,P＝0.048),left anterior cingulate gyrus(t＝6.127,P＝0.000),right anterior cingulate gyrus(t＝5.673,P＝0.000), left anterior cingulum(t＝7.067,P＝0.000),right anterior cingulum(t＝9.934,P＝0.000), left centrum semiovale(t＝4.320,P＝0.000),peripheric white matter of left anterior angle(t＝2.778,P＝0.012),peripheric white matter of right anterior angle(t＝2.316,P＝0.033),peripheric white matter of left posterior angle (t＝6.012,P＝0.000),peripheric white matter of right posterior angle (t＝7.256,P＝0.000),left parahippocampal gyrus(t＝4.055,P＝0.001),right parahippocampal gyrus(t＝4.134,P＝0.001),left external capsule(t＝2.619,P＝0.017), and right external capsule(t＝2.548,P＝0.020).Compared with control group,significant higher ADC values were found in multiple regions as below in patients in OSAHS:white matter of right frontal lobe (t＝-2.793,P＝0.012),trunk of corpus callosum(t＝-2.741,P＝0.013),splenium of corpus callosum(t＝-4.871,P＝0.000),left anterior cingulate gyrus (t＝-15.359,P＝0.000),right anterior cingulate gyrus(t＝-14.452,P＝0.000),right anterior cingulum(t＝-2.863,P＝0.010),left centrum semiovale(t＝-2.263,P＝0.036), and peripheric white matter of left anterior angle(t＝-2.291,P＝0.034).After analyzing correlation between sleep architecture and cognitive disfunction in patients with OSAHS,it was found thatⅢstage plusⅣstage/total sleep time (TST)not only had a significant positive correlation both with right anterior cingulum and with peripheric white matter of right posterior angle,but also had a significant negative correlation with fight anterior cingulum.We also found that the patients in OSAHS had lower memory quotient(MQ), pictures recollection values,recognition values,vision reproduction values,and numbers reciting values than healthy controls(t＝2.318,P＝0.026;t＝2.376, P＝0.023;t＝2.195,P＝0.034;t＝2.828,P＝0.007;t＝3.077,P＝0.004).After analyzing correlation between WMS values and cognitive disfunction in patients with OSAHS,it was found that pictures recollection values,had a significant positive correlation with peripheric white matter of right posterior angle(r＝0.741, P＝0.036),both vision reproduction values and MQ had a significant positive correlation with white matter of fight frontal lobe(r＝0.450,P＝0.030;r＝0.450, P＝0.030).At last,We found that the patients in OSAHS had lower MMSE values and calculation values than healthy controls(t＝2.484,P＝0.016;t＝2.241,P＝0.029)CONCLUSIONS:Firstly,It was found in China for the first time that the patients with OSAHS had extensive white matter microstructural lesions,involving in internuncial fibers,commissural fibers and projection fibers.Secondly,gray matter such as bilateral cingulate gyrus and parahippocampal gyrus,which were thought to relate with cognitive function,was also damaged.Thirdly,DTI can reveal white matter microstructural lesions in the early stage.Fourthly,FA values was more sensitive than ADC values for white matter microstructural lesions.Fifthly,the patients with OSAHS had unstuck sleep architecture,severity of which correlated with the degree of white matter microstructural lesions.Sixthly,The patients with OSAHS had worse memory function and short-term memory which correlated with white matter microstructural lesions.Finally,both cognitive function and calculation ability was damaged in patients with OSAHS.Chapter 3 Mierostructural lesions in normal-appearing white matter in patients with LI by DTIOBJECTIVES:To investigate microstructural lesions in normal-appearing white matter both in patients with lacunar infarction(LI).METHODS:FA and ADC values was examined in ROI respectively,and then DTT of corpus callosum was operated.The datas were dealed with SPSS 13.0,and numeric variables were represented by mean+standard deviation((?)±SD) Independent-samples t test was applied when comparing LI group with controls.As usual,it was thought to have statistical significance when P＜0.05. RESULTS:Compared with control group,significant lower FA values were found in multiple regions from normal-appearing white matter or gray matter in patients with LI:white matter of left frontal lobe(t＝2.857,P＝0.007),white matter of right frontal lobe(t＝2.604,P＝0.013),splenium of corpus callosum(t＝3.177,P＝0.003 ),left anterior cingulum(t＝2.198,P＝0.034 ),right anterior cingulum(t＝2.495, P＝0.017),left anterior limb of internal capsule(t＝5.483,P＝0.000),right anterior limb of internal capsule(t＝4.619,P＝0.000),left genu of internal capsule(t＝3.601,P＝0.001), right genu of internal capsule(t＝2.907,P＝0.006 ),left posterior limb of internal capsule(t＝3.243,P＝0.002),right posterior limb of internal capsule(t＝2.359,P＝0.023), left centrum semiovale(t＝3.167,P＝0.003),right centrum semiovale(t＝2.369,P＝0.023),left optic radiation(t＝3.167,P＝0.003),right optic radiation(t＝4.220,P＝0.000),peripheric white matter of left anterior angle(t＝3.012,P＝0.004),peripheric white matter of right anterior angle(t＝2.112,P＝0.041),peripheric white matter of left posterior angle(t＝2.193,P＝0.034 ),left parahippocampal gyrus(t＝2.347,P＝0.024), right parahippocampal gyrus(t＝2.103,P＝0.042),right external capsule(t＝3.006,P＝0.005).Compared with control group,significant higher ADC values were found in multiple regions from NAWM or normal-appearing gray matter(NAGM) in patients with LI:trunk of corpus callosum(t＝-3.272,P＝0.002),splenium of corpus callosum (t＝-2.413,P＝0.021),left anterior limb of internal capsule(t＝-3.059,P＝0.004), right anterior limb of internal capsule(t＝-3.831,P＝0.000),right genu of of internal capsule(t＝-2.530,P＝0.015),left posterior limb of internal capsule(t＝-3.047,P＝0.004),right posterior limb of internal capsule(t＝-2.634,P＝0.012),left centrum semiovale(t＝-2.819,P＝0.007),peripheric white matter of left posterior angle (t＝-2.075,P＝0.044),left parahippocampal gyrus(t＝-2.496,P＝0.017).DTT for corpus callosum indicated that the fibers in frontal forceps and genu were found sparse,thin and discontinuous.CONCLUSIONS:Firstly,it was found that the patients with LI had extensive microstructural lesions in NAWM.Secondly,NAGM such as bilateral parahippocampal gyrus,which were thought to relate with cognitive function,was also damaged.Finally,DTT for corpus callosum indicated that the fibers in frontal forceps and genu were found sparse,thin and discontinuous.Chapter 4 Microstruetural lesions in normal-appearing white matter in patients with relapsing-remitting MS by DTIOBJECTIVES:To investigate microstructural lesions in NAWM in patients with relapsing-remitting MS.METHODS:FA and ADC values was examined in ROI respectively,and then DTT of corpus callosum was operated.The datas were dealed with SPSS 13.0,and numeric variables were represented by mean±standard deviation((?)±SD) Independent-samples t test was applied when comparing LI group with controls.As usual,it was thought to have statistical significance when P＜0.05.RESULTS:Compared with control group,the patients with relapsing-remitting MS had significant lower FA values in multiple regions from NAWM or NAGM as below:white matter of left frontal lobe(t＝3.638,P＝0.002),white matter of right frontal lobe(t＝3.181,P＝0.005),left centrum semiovale(t＝3.273,P＝0.004),right centrum semiovale(t＝2.201,P＝0.040),left optic radiation(t＝2.281,P＝0.034),right optic radiation(t＝3.380,P＝0.003 ),peripheric white matter of left anterior angle (t＝4.905,P＝0.000),peripheric white matter of right anterior angle(t＝3.674,P＝0.002),peripheric white matter of left posterior angle(t＝2.636,P＝0.016),peripheric white matter of right posterior angle(t＝4.714,P＝0.000),left thalamus (t＝2.325,P＝0.031),right thalamus(t＝2.398,P＝0.026),right parahippocampal gyrus (t＝2.660,P＝0.015). Compared with control group,the patients with relapsing-remitting MS had significant higher ADC values in multiple regions from normal-appearing white matter or gray matter as below:white matter of right frontal lobe(t＝-3.797,P＝0.001),genu of corpus callosum(t＝-2.688,P＝0.014),trunk of corpus callosum(t＝-4.547, P＝0.000 ),splenium of corpus callosum(t＝-3.211,P＝0.004 ),left centrum semiovale (t＝-4.044,P＝0.001 ),right centrum semiovale(t＝-4.461,P＝0.000),peripheric white matter of left posterior angle(t＝-4.487,P＝0.000),peripheric white matter of right posterior angle(t＝-2.652,P＝0.015 ),left parahippocampal gyrus(t＝-2.548,P＝0.019), right parahippocampal gyrus(t＝-2.269,P＝0.034).DTT for corpus callosum indicated that corpus callosum fiber had sparse align,enlarged crevice,and discontinuance in the trunk.CONCLUSIONS:Firstly,it was found that the patients with relapsing-remitting MS had extensive microstructural lesions in NAWM from some regions which correlated with cognitive function,involving in bilateral white matter of frontal lobe, centrum semiovale,corpus callosum,anterior cingulum,and especially peripheric white matter of anterior angle and posterior angle.Secondly,NAGM such as bilateral parahippocampal gyrus in the patients with relapsing-remitting MS,which were thought to relate with cognitive function,was also damaged.Finally,DTT for corpus callosum indicated that corpus callosum fiber had sparse align,enlarged crevice,and discontinuance in the trunk.GENERAL CONCLUSIONS:1.It was indicated that the density of white matter fibers were unanimous in bilateral brain.2.Anisotropy varied in each brain structure,generally white matter had remarkable higher anisotropy compared with gray matter.3.There was different anisotropy in three types nerve fibres:commissural fibers had the highest anisotropy,the following were projection fibers,and internuncial fibers were the lowest.4.It was found in China for the first time that the patients with OSAHS had extensive white matter microstructural lesions,involving in internuncial fibers, commissural fibers and projection fibers.5.Gray matter such as bilateral cingulate gyrus and parahippocampal gyrus, which were thought to relate with cognitive function,was also damaged.6.DTI can reveal white matter microstructural lesions in the early stage.Fourthly, FA values was more sensitive than ADC values for white matter microstructural lesions.7.The patients with OSAHS had unstuck sleep architecture,severity of which correlated with the degree of white matter microstructural lesions.8.The patients with OSAHS had worse memory function and short-term memory which correlated with white matter microstructural lesions.9.Both cognitive function and calculation ability was damaged in patients with OSAHS.10.It was found that the patients with LI had extensive microstructural lesions in NAWM.11.NAGM such as bilateral parahippocampal gyrus,which were thought to relate with cognitive function,was also damaged.12.DTT was able to indicate directly that corpus callosum in LI had been damaged.13.It was found that the patients with relapsing-remitting MS had extensive microstructural lesions in NAWM from some regions which correlated with cognitive function,especially in peripheric white matter of anterior angle and posterior angle.14.NAGM such as bilateral parahippocampal gyrus in the patients with relapsing-remitting MS,which were thought to relate with cognitive function,was also damaged.15.DTT indicated that corpus callosum had remarkable damage in RRMS.INNOVATIVE FEATURES1.It was found by DTI that the patients with OSAHS had extensive white matter microstructural lesions,and some gray matter relating with cognitive function was also damaged.2.It was found that the patients with LI had extensive microstructural lesions in NAWM which was difficult to detect by conventional MRI.3.DTI is helpful to detect damage to the visual pathways in the early stage.