【作者】 陈宇；

【导师】 冯敢生； 徐坚民；

【作者基本信息】 华中科技大学 ， 影像医学与核医学， 2009， 博士

【摘要】 第一部分梗塞后抑郁症(PSD)的脑形态学研究目的通过测量梗塞后抑郁(PSD)组、梗塞非抑郁组(CONT)及正常志愿者(NORM)组3组受试者的双侧海马及杏仁核大小以探讨PSD的脑形态学基础，并分析PSD患者梗塞灶部位与抑郁症的关系。方法研究11例梗塞后抑郁症(PSD)患者及13例脑梗塞无抑郁症(CONT)患者和15例健康志愿(NORM)者，运用容积分析软件测量两侧海马及杏仁核体积。结果1．各组均显示海马及杏仁核体积左侧＜右侧，其中PSD组与NORM组两侧海马及杏仁核体积差异有显著性，左侧海马：右侧海马(PSD组：t=-3，P=0．013；NORM组：t=-7．46，P=0．000)，左侧杏仁核：右侧杏仁核(PSD组：t=-5．04，P=0．001；NORM组：t=-3．28，P=0．005)，而CONT组两侧海马及杏仁核体积差异没有显著性；2．PSD组中两侧海马及杏仁核体积均明显＜CONT组(海马左右：P=0．001，0．040；杏仁核左右：P=0．000，0．000)，PSD组右侧海马体积明显＜NORM组(P=0．034)；CONT组双侧杏仁核体积均明显＞NORM组(P=0．000，0．000)；3．PSD患者双侧海马及杏仁核体积缩小与HAMD抑郁量表评分均缺乏相关性(P＞0．05)；4．PSD、CONT、NORM 3组杏仁核体积的偏侧化指数(LI)比较有统计学差异(p=0．04)，主要是PSD组与CONT组统计学差异较明显；5．梗塞灶位于额颞顶叶皮质区和脑干及小脑时PSD组与CONT组有显著统计学差异，PSD组双侧梗塞灶部位与额极最短距离均小于CONT组，但无明显统计学差异；6．从相关系数大小来看，各指标与PSD相关性从大到小顺序是脑干及小脑＞左侧杏仁核＞右侧杏仁核＞额颞顶叶皮质区＞左侧海马＞右侧海马＞枕叶皮质区＞左额极距离＞后部＞右额极距离＞左额叶＞基底核区＞海马杏仁核＞前部＞放射冠区＞右额叶。7．同时建立了回代效果好的判别方程。结论海马及杏仁核体积异常可能构成梗塞后抑郁症的神经生物学基础，脑干、小脑、额颞顶叶皮质区等部位的脑梗塞与双侧杏仁核、海马体积与PSD具有高相关性，说明边缘系统和脑干、小脑、额颞顶叶皮质区梗塞在抑郁症的发病机理中起着重要作用。第二部分梗塞后抑郁症(PSD)的功能性磁共振成像研究目的采用功能性磁共振方法研究梗塞后抑郁症(PSD)患者对不同性质情绪图片的差异脑激活反应，以探讨PSD患者的脑活动特征。方法对11名梗塞后抑郁症(PSD)患者、13例脑梗塞无抑郁症(CONT)患者和15例健康志愿(NORM)者进行国际情绪图片系统中中性-正性-负性三组图片刺激的脑功能磁共振成像(fMRI)扫描，任务为组块设计，用神经功能影像分析(AFNI)软件处理影像数据。结果1．PSD组、CONT组及NORM组观察中性-正性-负性情绪图片时激活脑区主要有额叶皮层-皮层下网状系统、基底节区(丘脑、苍白球、尾状核)和边缘系统(海马、海马旁回、杏仁核)、岛叶、颞叶、枕叶、脑干及小脑半球，其中负性图片激活脑区面积大于正性图片。2．PSD组组内比较：正性—中性有显著差异的负性激活脑区有双侧额上、中、下回、中央前回、顶上小叶、楔前叶、角回、扣带回压部、岛叶、丘脑、豆状核、海马、海马旁回、颞上、中回、枕叶视皮质区、脑桥、中脑及小脑半球，右侧杏仁核。正性激活脑区有双侧枕叶；负性—中性有显著差异的负性激活脑区有双侧额上、中回、中央前回、楔前叶、角回、缘上回、扣带回前部及压部、胼胝体、岛叶、丘脑、尾状核、豆状核、海马旁回、海马、枕叶视皮质区、脑桥、中脑及小脑半球。正性激活脑区有左侧杏仁核、背侧丘脑及岛叶，双侧枕叶；负性—正性有显著差异的负性激活脑区有双侧额上、中回、豆状核、胼胝体、扣带回前部，左侧岛叶，右侧尾状核。正性激活脑区有双侧额上、中回、中央前回、楔前叶、扣带回压部、岛叶、丘脑、尾状核、豆状核、杏仁核、枕叶视皮质区及小脑半球。3．PSD组减NORM组组间比较：识别中性图像有显着差异的负性激活脑区有双侧顶上小叶、扣带回及胼胝体压部，左额中回、右海马旁回、海马、丘脑、右缘上回。正性激活脑区有右楔叶、枕叶视皮质区，左侧小脑半球。识别正性图像有显着差异的负性激活脑区有双侧海马旁回、海马、背侧丘脑以及顶上小叶、楔前叶、颞中、下回、中脑及小脑半球，右侧额中、下回、豆状核、岛叶。正性激活脑区有双侧小脑半球、枕叶视皮质区及右侧顶叶。识别负性图像有显着差异的激活脑区有双侧海马旁回、丘脑、楔叶、枕叶视皮质区及小脑半球，右侧海马、杏仁核、颞中、下回及顶叶。负性激活脑区有左侧额中、下回、顶上小叶，右顶下小叶。4．PSD组减CONT组组间比较：识别中性图像有显着差异的正性激活脑区有双侧颞上回、颞中回、枕叶视皮质区，左侧额中回、额下回、豆状核、岛叶，右侧海马旁回、海马、顶上小叶。负性激活脑区有左侧额上、中回；识别正性图像有显着差异的正性激活脑区有双侧海马旁回(右侧明显)、额下回、楔叶、颞上、中、下回、梭状回、扣带回压部、枕叶视皮质区，右顶上小叶。负性激活脑区有左侧额上、中回；识别负性图像有显着差异的激活脑区有右海马、海马旁回、顶上小叶，左颞中回、颞下回，正性激活脑区有枕叶视皮质区。结论PSD与边缘系统(海马、海马旁回、杏仁核)以及额中回、扣带回、丘脑、岛叶、脑干及小脑半球等有密切关系，上述脑区的损害涉及以边缘系统-皮层-纹状体-苍白球-丘脑神经环路为主的多条神经环路的结构和功能异常，可能参与了PSD的病理生理机制。第三部分梗塞后抑郁症(PSD)的脑白质完整性研究——扩散张量成像(DTI)及其方法学研究第一节梗塞后抑郁症(PSD)的磁共振扩散张量成像(DTI)研究目的采用磁共振扩散张量成像(DTI)技术研究梗塞后抑郁症(PSD)的脑白质FA值改变及其意义。方法采用DTI感兴趣区(ROI)法和基于体素的分析方法(voxelbased measure，VBM)对11名梗塞后抑郁症(PSD)患者、13例脑梗塞无抑郁症(CONT)患者和15例健康志愿(NORM)者进行各部位脑白质FA值测量及脑激活功能区的比较，研究PSD患者的DTI表现特点。结果1．PSD组与NORM组FA值有显著统计学差异(P＜0．05)的部位有双侧额叶、顶叶、左侧内囊前、后肢、右侧枕叶。PSD组与CONT组FA值有显著统计学差异(P＜0．05)的部位有左侧额叶、顶叶、左侧内囊前、后肢，扣带回前部。CONT组与NORM组FA值有显著统计学差异(P＜0．05)的部位仅右侧丘脑。2．PSD组一CONT组和PSD组—NORM组顶叶及内囊前肢2个部位FA值的偏侧化指数(LI)比较统计学差异较明显(顶叶Pp-c=0．006、Pp-n=0．032；内囊前肢Pp-c=0．014、Pp-n=0．001)。其余部位偏侧化指数(LI)比较无统计学差异。3、PSD组—NORM组FA值有显著差异的激活脑区有双侧额上、中回、顶叶、扣带回前部及体部、胼胝体前部及压部、岛叶、丘脑、豆状核、颞叶、枕叶及小脑半球。以胼胝体、扣带回明显。PSD组—CONT组FA值的有显著差异的激活脑区有双侧额顶叶内侧及扣带回体部交界区，右侧颞叶，左侧枕叶。以双侧额顶叶近中线处及扣带回体部交界区稍明显。CONT组—NORM组FA值有显著差异的激活脑区仅有双侧侧脑室前后角周围少许白质(额叶、顶叶)、岛叶、胼胝体前部、少许颞叶。4．非线性标准化图像要明显比线性标准化图像配伍对位更加准确。结论PSD组与CONT组、NORM组FA值差异显著的部位主要有左侧额叶、顶叶，左侧内囊前、后肢，扣带回前部及胼胝体、扣带回及额顶叶近中线的脑回，提示这几个部位可能与脑梗塞患者好发PSD有关。DTI为我们活体精确评价PSD脑白质细微结构改变提供了一个较好的平台，从而有望为临床预测、治疗及评估PSD疗效提供新的方法和思路。第二节磁共振扩散张量成像(DTI)方法学研究——纤维追踪法对脑白质老化的研究初探(90例定量DTI分析)目的采用DTI纤维追踪法定量比较不同年龄组正常自愿者椎体束从大脑脚到中央前回部分(PRPT)FA值的差别及其意义。方法将90例正常志愿者(20—83岁)按年龄分为6组进行基于纤维追踪的定量DTI研究，图像标准化后分析各组PRPT的FA值与年龄组老化的关系。结果各年龄组双侧PRPT的FA值分布相似，最低点在放射冠处，最高峰为内囊后肢；各段FA值随年龄增长呈下降趋势，表明这些部位的纤维随年龄增长发生了老化，其中以额叶老化最为明显；并发现额叶及大脑脚白质老化过程中存在突然变化(P＜0．0001，p=0．0068)。结论DTI可以作为评价脑组织细微结构变化和老化过程的敏感工具；额叶及大脑脚白质老化过程中存在突变，是否脑生理上老化的标志?，有待进一步研究。更多还原

【Abstract】 PartⅠThe study the characteristics of brain morphology of patientswith post-stroke depressionObjective To investigate the volume change of the amygdala and hippocampus inpatients with post-stroke depression(PSD) and analyze the relationship of PSD and anatomyposition of infarct lesion using MR imaging.Methods Quantitative MRI about volumes of the amygdala and hippocampus wasstudied in 11 patients with post-stroke depression and compared with 13 stroke patientswithout depression(CONT) and 15 age-matched controls(NORM).Results 1.PSD group and NORM group exhisited similar significant hippocampusand amygdala asymmetry(left smaller than right).2.The volume of the bilateralhippocampus and amygdala in PSD group was significantly smaller than that in CONTgroup (P＜0.05).The volume of right hippocampus in PSD group was smaller than that inNORM group(P=0.034);3.There was no correlation between the hippocampus andamygdala volume abnormalities and the score of HAMD in PSD patients (P＞0.05);4.Thedifferences of Laterality Index(LI) of amygdala volume among PSD group、CONT groupand NORM group were statistically difference (p = 0.04),especially in PSD-CONT group.;5.PSD group and NORM group has a significant statistical difference when infarct lesionswere located in frontal-temporal-parietal cortex and the brain stem and cerebellum.The shortest distance between prefrontal cortex and lesions in PSD group is shorter than thatin CONT group,but no significant statistical difference;6.The size of the correlationcoefficient between all targets and PSD are the brain stem and cerebellum＞the size of leftamygdala＞the size of right amygdala＞frontal-temporal-parietal cortex＞the size of lefthippocampus＞the size of right hippocampus＞occipital cortex＞distance between leftprefrontal cortex and lesion＞posterior cerebral＞distance between right prefrontal cortexand lesion＞left frontal lobe＞basal ganglia area＞hippocampus and amygdale area＞anterior cerebral＞corona radiata district＞right frontal lobe;7.A good discriminantequation was established.Conclusion Cerebral infarction in brainstem,cerebellum,frontal- temporal-parietalcortex and the volume of amygdale and hippocampus shows well correlation with the PSD,These findings support the hypothesis that the hippocampus and amygdalawithin limbic system-cortical networks may play a crucial role in the pathogenesis ofpost-stroke depression.PartⅡThe study of brain functional magnetic resonance imaging onpost-stroke depressionObjective To explore the characteristics of brain activity in patients with post-strokedepression (PSD) by probing the differences of neural activation associated with reactivityto different affective stimuli pictures using functional MR imaging (fMRI).Methods Neural responses to neutral,positive,negative emotional pictures (fromInternational Affective Pictures System,IAPS) stimuli based on block-design weremeasured by functional magnetic resonance imaging(fMRI) in 11 patients with post-strokedepression PSD、13 stroke patients without depression(CONT) and 15 age-matched healthy controls(NORM).the fMRI data were analyzed by using Analysis of FunctionalNeuroimages (AFNI) software.Results 1.Observing the neutral,positive,negative emotional pictures,All patientsin PSD group、CONT group and NORM group showed mainly activated areas using fMRIinclude the prefrontal cortex - subcortical reticular system、basal ganglia (thalamus,globuspallidus,caudate nucleus) and limbic system (hippocampus,parahippocampal gyrus,amygdale)、insula、temporal lobe、occipital lobe、brain stem and cerebellum.2.PSDgroup Comparison:Positive - neutral showed mainly activated areas include bilateralsuper-,mid- and infer- frontal gyrus,precentral gyrus,superior parietal lobule,precuneus,angular gyrus,splenium cingulate gyrus,insula,thalamus,lentiform nucleus,hippocampus,parahippocampal gyrus,super-,mid- temporal gyrus,occipital visual cortex,pons,midbrain,cerebellar hemispheres,right amygdala.(negative) and bilateral occipitallobe(positive);Negative-neutral showed mainly activated areas include bilateral super-,mid- frontal gyrus,precentral gyrus,superior parietal lobule,precuneus,angular gyrus,,supramarginal gyrus,cingulate gyrus,corpus callosum,insula,thalamus,caudate nucleus,lentiform nucleus,hippocampus,parahippocampal gyrus,occipital visual cortex,pons,midbrain,cerebellar hemisphere.(negative) and left amygdala,dorsal thalamus and insula,bilateral occipital lobe(positive);Negative-positive showed mainly activated areas includebilateral super-,mid- frontal gyrus,lentiform nucleus,corpus caliosum,anterior cingulategyrus,left insula,right caudate nucleus(negative) and bilateral super-,mid- frontal gyrus,precentral gyrus,precuneus,splenium cingulate gyrus,insula,thalamus,caudate nucleus,lentiform nucleus,amygdala,occipital visual cortex and cerebellum(positive).3.PSD-NORM group inter-group comparison:Identify neutral picture showed mainly activatedareas include bilateral superior parietal lobule,cingulate gyrus,corpus callosum,leftmid-frontel gyrus,right parahippo- campal gyrus,hippocampus,thalamus,rightsupramarginal gyrus(negative) and right cuneus,occipital visual cortex,left cerebellarhemisphere(positive).;Identify positive picture showed mainly activated areas include bilateral parahippocampal gyrus,hippocampus,dorsal thalamus,superior parietal lobule,precuneus,,mid-infer-temporal gyrus,midbrain,cerebellar hemisphere,right mid-infer-frontel gyrus,,lentiform nucleus,insular(negative) and bilateral cerebellar hemisphere,occipital visual cortex and right parietal lobe(positive).;Identify negative picture showedmainly activated areas include bilateral parahippocampal gyrus,thalamus,cuneus,occipitalvisual cortex and cerebellar hemisphere,right hippocampus,amygdala,temporal,parietallobe(positive) and left mid-infer- frontal gyrus,superior parietal lobule,right inferiorparietal lobule.(negative).4.PSD-CONT group inter-group comparison:Identify neutralpicture showed mainly activated areas include bilateral super-mid- temporal gyrus,occipital visual cortex,left mid-infer- frontal gyrus,lentiform nucleus,insula,righthippocampaus,parahippocampal gyrus,superior parietal lobule(positive) and leftsuper-mid- frontal gyrus,(negative);Identify positive picture showed mainly activatedareas include bilateral parahippocampal gyrus(right obviously),inferior frontal gyrus,cuneus,super-mid-infer- temporal gyrus,fusiform gyrus,splenium cingulate gyrus,occipital visual cortex,right superior parietal iobule,(positive) and left mid-infer- frontelgyrus(negative);Identify negative picture showed mainly activated areas include righthippocampus,parahippocampal gyrus,superior parietal lobule,left mid-infer- temporalgyrus (negative) and occipital visual cortex (positive).Conclusion Patients with PSD presented an close relationship with limbic system(hippocampus、parahippocampal gyrus、amygdala)、middle frontal gyrus、superiorparietal lobule、cingulate gyrus、the right dorsal thalamus、insula、the brain stem andcerebellar hemisphere,which may be involved in the mechanism of pathophysiology inPSD by demaging the structure and function of multiple neural loops,primarily in thelimbic system - cortex - the striatum - the globus pallidus - thalamus neural loop. PartⅢThe research of the integrity of brain white matter in post-stroke depression(PSD) Diffusion tensor imaging (DTI) and its methodsSection 1 The study of magnetic resonance diffusion tensor imaging(DTI) on post-stroke depression(PSD)Objective To investigate the FA value changes in brain white matter of patients withpost-stroke depression (PSD) using magnetic resonance diffusion tensor imaging (DTI).Methods Diffusion tensor MR imaging were performed in 11 patients withpost-stroke depression (PSD)、13 stroke patients without depression(CONT) and 15age-matched healthy controls(NORM).The appearances of DTI in patients with PSD wereanalyzed by comparing the FA values of brain white matter and brain activation areasamong three groups based on regions of interest (ROI) methods and voxel-based measuremethods (VBM).Results 1.The areas of FA values having statistically significant differences (P＜0.05)included both parts of the frontal lobe、parietal lobe、left internal capsule、right occipitallobe in PSD-NORM group,left frontal lobe、left parietal lobe、left internal capsule、theanterior part of cingulate gyrus in PSD-CONT group and only right thalamus inCONT-NORM group.2.The areas of the Laterality Index (LI) of FA values havingstatistically significant differences (P＜0.05) included parietal lobe and internal capsule inPSD-CONT Group and PSD-NORM group (parietal Pp-c = 0.006,Pp-n = 0.032;internalcapsule forelimb Pp-c = 0.014,Pp-n = 0.001).The remaining parts of unilateral index (LI)showed no statistical difference.3.The activated cerebral regions having statisticallysignificant differences included both parts of superior-middle frontal gyrus、parietal lobe、cingulate gyrus、corpus callosum、insula、thalamus、lenticularnucleus、temporal lobe、occipital lobe and cerebellum in PSD-NORM group,bilateral inner parts of frontal lobeand parietal lobe、the body of cingulate gyrus、right temporal lobe、left occipital lobe inPSD-CONT group and a little white matter around lateral cerebral ventricle (frontal lobe, parietal lobe),insula,anterior corpus callosum,temporal lobe in CONT-NORM group.4.The images of nonlinear normalization were more accurate and better than that of linearnormalization.Conclusion Compared with patients in CONT group and NORM group,Patients withPSD presented an close relationship with the left frontal lobe、parietal lobe、left internalcapsule、cingulate gyms、corpus callosum and bilateral inner parts of frontal lobe andparietal lobe.DTI provides a good platform that can more accurately evaluate themicrostructural changes of brain white matter in vivo,which is expected to offer a newmethod and idea for prediction、treatment and assessment of clinical efficacy in patientswith PSD.Section 2 The study of methods of magnetic resonance diffusion tensorimaging (DTI)—White matter fiber tracking method for the study ofaging:ninety cases of quantitative diffusion tensor imaging (DTI) analysisObjective To investigate the difference and significance of Fractional anisotropy (FA)of precentral portion of the pyramidal tract (PRPT,ie from cerebral peduncle to precentralgyrus) in different age-groups health volunteers using quantitative diffusion tensorimaging (DTI) based on fiber tractography.Methods Quantitative DTI based on fiber tractography were performed in 90 healthvolunteers (20-83years) divided into 6 age groups at a 1.5T MR scanner.Standardizedimages data were analyzed for the relationship between FA values of PRPT and aging.Results The FA value of bilateral PRPT in each age group distribute similarly,inwhich FA value of corona radiata is the lowest and the posterior limb of the internal capsuleis the highest;The FA values of sections is declining with aging,showed the fibers of these parts had significantly aging and the most obvious aging part is the frontal lobe;we foundthe procedure of aging in the frontal lobe and cerebral peduncle does exist mutationperiod(P＜0.0001,P=0.0068).Conclusion Diffusion tensor imaging (DTI) is a sensitive method for detecting themicrostructural changes and aging process of brain white matter;Whether the Mutation ofaging in the frontal lobe and cerebral peduncle is the physical signs of aging,it should befurther examined.更多还原