阿尔茨海默病的MRI结构与功能研究

发布时间：2018-05-09 18:37

本文选题：轻度认知障碍 + 阿尔茨海默病　；参考：《复旦大学》2014年博士论文

【摘要】：第一部分aMCI与轻度AD基于体素的形态学MRI纵向研究目的：探讨遗忘型轻度认知障碍(amnestic-type mild cognitive impairment,aMCI)、轻度阿尔茨海默氏病(Alzheimer's disease, AD)患者相对于正常老年人灰质体积变化特点。方法：采用3.0磁共振,对37例aMCI患者、30例轻度AD患者及30例正常老年人进行三维T1WI扫描,运用SPM8分析软件,采用基于体素的形态学测量法(Voxel-based morphometry, VBM)对扫描获得的结构图像,进行全脑灰质体积基于体素的统计学比较。其中17例aMCI患者一年后纵向随访。结果：与正常对照组比较,aMCI组双侧颞中、下回,海马、海马旁回、尾状核、壳核、缘上回、丘脑及双侧枕叶,此外还见于左侧中央后回、角回、右侧岛叶、中央前回及额上回灰质萎缩,其差异具有统计意义。轻度AD组的双侧颞中回、额中回、额上回、枕叶梭状回、左侧中央后回、楔前叶、右侧缘上回、中央前回及鳃盖、顶上叶、侧枕皮层及额下回灰质萎缩,其差异具有统计意义。轻度AD组与aMCI组比较,脑灰质萎缩区主要位于右侧楔前叶及侧枕皮层,左侧枕下回,另还可见于双侧缘上回、额中回、左侧旁扣带回、角回、颞下回、右侧壳核、额下回、颞上回、枕中回及脑干(P0.05, FDR-corrected, Cluster100体素)。纵向随访中,双侧额颞顶枕叶进一步萎缩(P0.05, uncorrected, Cluster100体素)。结论：通过基于体素的形态学研究能够发现aMCI期及轻度AD患者脑灰质细微结构的萎缩,从而在疾病的早期提供诊断支持,为尽早的干预治疗提供帮助。第二部分aMCI与轻度AD基于体素的形态学脑PASL纵向研究目的：应用脉冲动脉自旋标记(pulsed arterial spin labeling, PASL)技术、探讨aMCI、轻度AD患者脑血流灌注的变化特点。方法：采用3.0磁共振,采集静息状态下37例aMCI患者、30例轻度AD患者及30例正常老年人动脉自旋标记的灌注成像数据,计算其相对脑血流量。其中17例aMCI患者一年后纵向随访。结果：与正常对照组比较,aMCI组双侧后扣带回及楔前叶血流增加,其差异具有统计意义。轻度AD组的左侧顶上下回、角回、额中回及右侧颞上回血流减低,其差异具有统计意义((Alphasim corrected,p0.05,最小cluster体积k=1632体素)。纵向随访中,双侧额颞顶枕叶、丘脑、扣带回均有血流灌注增加及减低的改变,血流增加略多,尤其是额叶(p0.05,uncorrected,k≥100体素)结论：动脉自旋标记的灌注成像为检测MCI及AD患者异常灌注改变提供了一种有价值的方法,MCI组与AD组患者的灌注异常与其脑结构和功能的改变密切相关。第三部分aMCI与轻度AD基于体素的全脑DTI纵向研究目的：应用磁共振弥散张量成像(Diffusion tensor imaging, DTI)技术、探讨aMCI、轻度AD患者脑白质微观结构的变化特点。方法：采用3.0磁共振,对37例aMCI患者、30例轻度AD患者及30例正常老年人进行DTI检查,运用基于纤维束的空间统计(Tract-basedspatial statistics,TBSS)软件以比较白质结构的差异。17例aMCI患者一年后纵向随访。结果：与正常对照组比较,aMCI组右侧胼胝体膝部,双侧下额枕束、上纵束、右侧的内囊前肢、前丘脑放射及左侧下纵束的脑白质FA值减低；FA值增高区大部分位于右侧的皮质脊髓束、前丘脑放射,其次是于右侧上纵束、扣带束及其海马部分,另外还见于双侧下额枕束、右侧前丘脑放射、右侧胼胝体辐射线枕部及左侧上纵束。脑白质MD增加区主要位于左侧半球,集中于左侧下纵束、钩状束、下额枕束、上纵束及上纵束颞部、皮质脊髓束、右侧上纵束及上纵束颞部及钩状束。脑白质MD减低区见于小部分右侧皮质脊髓束,其差异具有统计意义(P0.05,t值2-6,Corrected)。轻度AD组的左侧上放射冠、左侧上纵束、双侧下额枕束、右侧扣带束的海马部、外囊以及穹隆、左侧前丘脑放射、穹隆、终纹、外囊、扣带束脑白质FA值减低;FA增高区大部分位于左侧皮质脊髓束、前丘脑放射、右侧上纵束,还可见于右侧钩形束、扣带束及其海马区、下额枕束、右侧前丘脑放射、右侧胼胝体辐射线枕部、双侧下纵束、左侧扣带束。脑白质MD增加区体素明显增大,主要位于左侧半球,集中在左侧上纵束、皮质脊髓束以及右侧皮质脊髓束的小部分。脑白质MD减低区见于小部分右侧皮质脊髓束。其差异具有统计意义(P0.05,t值2-6；Corrected)。纵向随访中,脑白质FA值降低明显,集中在左侧上放射冠及下纵束,少许右侧扣带束及上纵束FA值增高。MD增高明显,以左侧枕钳及右侧扣带束为主,少许右侧扣带束及上纵束MD减低。(P0.05, uncorrected, Cluster100体素)结论：DTI能够观察AD白质微观结构的变化,这些变化可以成为诊断疾病的生物学标记物。第四部分aMCI与轻度AD的静息态fMRI纵向研究目的：联合应用低频波振幅分析(Amplitude of Low Frequency Fluctuation, ALFF)和种子点相关分析(seed-basedcorrelation analysis),探讨aMCI、轻度AD患者静息态脑功能连接的变化特点。方法：采用3.0磁共振,对37例aMCI患者、30例轻度AD患者及30例正常老年人,进行静息态fMRI扫描。利用SPM8软件对于所有数据进行预处理,用REST及DPARSF软件进行低频波振幅分析,比较病患组与正常组具有显著差异的脑区,提取该脑区的峰值点作为种子点,以4mm为半径做全脑功能连接,提取种子点做Pearson分析。结果：与正常对照组比较,aMCI组ALFF增高区位于右侧额上中回；ALFF降低区位于右侧额中回、左侧楔前叶。轻度AD组的ALFF增高区位于右侧胼胝体,左侧前运动皮层、额上回,ALFF降低区位于右侧直回,左侧扣带回、后扣带回、楔前叶,其差异具有统计意义。轻度AD组与aMCI组比较,ALFF曾高区位于右侧辅助运动区及额叶,左侧中央前回、中央旁小叶、扣带回、辅助运动区,还见于右侧中央前回、额上回,左侧中央后回；ALFF降低区位于双侧小脑、左侧额下回、枕上回、枕中回(P0.01,uncorrected,K≥10体素)。aMCI组的默认网络功能连接强度增高区位于双侧楔前叶,中央扣带回；减低区位于右侧颞叶。轻度AD组的默认网络功能连接强度增高区位于左侧岛叶,左额下回眶部；减低区位于双侧额叶,颞中回。轻度AD组与aMCI组比较,与默认网络功能连接强度增高区位于右额上回,减低区位于右额叶、前扣带回、中央扣带回、颞叶、缘上回,右额下回三角部、中央旁小叶(P0.01, uncorrected,体素)。17例aMCI病例一年后随访,右枕叶及距状皮层ALFF波幅减低(P0.05, FWE corrected,,K≥10体素)；右侧小脑默认网络连接强度下降,右侧顶下小叶、角回、额上回、额中回、左侧顶下小叶、颞下回、额中回连接强度增高(P0.01, uncorrected,K≥10体素)。结论：通过种子点相关分析可以在aMCI、轻度AD患者脑结构出现异常前发现静息态脑功能网络的特异性改变。
[Abstract]:Part one aMCI and light AD based on voxel based morphological MRI longitudinal study objective: To explore the characteristics of gray volume changes in patients with amnestic mild cognitive impairment (amnestic-type mild cognitive impairment, aMCI), mild Alzheimer's disease (Alzheimer's disease, AD) relative to normal elderly people. Method: 3 MRI, 37 cases of a MCI patients, 30 patients with mild AD and 30 normal aged people were scanned by three dimensional T1WI, using SPM8 analysis software, using the Morphin based morphometry (Voxel-based morphometry, VBM) to compare the scanned structural images of the whole brain, and 17 cases of aMCI patients were followed up one year later. Fruit: compared with the normal control group, the aMCI group had bilateral temporal, lower gyrus, hippocampus, parahippocampal gyrus, caudate nucleus, putamen, marginal gyrus, thalamus and bilateral occipital lobe, in addition to the left central posterior gyrus, the angular gyrus, the right Island leaf, the anterior central gyrus and the upper back of the frontal gyrus, with statistical significance. The bilateral temporal gyrus, the middle frontal gyrus, the upper frontal gyrus, the occipital of the mild AD group. The leaf spindle gyrus, the left central posterior gyrus, the anterior central lobe, the right margin of the upper gyrus, the anterior central gyrus and the gill cover, the upper lobe, the lateral occipital cortex and the lower frontal gyrus were atrophied, and the difference was statistically significant. The mild AD group was mainly located in the right anterior and lateral occipital cortex, the left occipital cortex, the left occipital gyrus, and the upper margin of the bilateral margin. Gyrus, lateral cingulate gyrus, angular gyrus, inferior temporal gyrus, right putamen, inferior frontal gyrus, upper temporal gyrus, occipital gyrus and brainstem (P0.05, FDR-corrected, Cluster100 voxel). Bilateral frontal and temporal occipital lobes were further atrophied (P0.05, uncorrected, Cluster100 voxel) during longitudinal follow-up. Conclusion: aMCI and mild AD can be found through morphological study based on voxel. The atrophy of the fine structure of the cerebral gray matter in the patient, thus providing diagnostic support in the early stage of the disease, and providing help for early intervention. Second part aMCI and the mild AD based Morphin based morphological brain PASL longitudinal study: the use of pulsed arterial spin labeling, PASL technology to explore the brain of aMCI, mild AD. Methods: 3 magnetic resonance imaging (3 MRI) were used to collect the perfusion imaging data of 37 patients with aMCI, 30 mild AD patients and 30 normal elderly patients with arterial spin labeling, and 17 cases of aMCI patients were followed up for one year after a year. The results were compared with the normal control group, and the bilateral posterior buckle in the aMCI group. The difference in the left top and lower gyrus of the mild AD group, the angular gyrus, the middle frontal gyrus and the right temporal gyrus were decreased, and the difference was statistically significant (Alphasim corrected, P0.05, the minimum cluster volume k=1632 voxel). In the longitudinal follow-up, the bilateral frontal and temporal occipital lobes, thalamus, cingulate gyrus had blood perfusion. The increase and reduction of blood flow increased slightly, especially in the frontal lobes (P0.05, uncorrected, k > 100 voxins) conclusion: arterial spin labeling perfusion imaging provides a valuable method for detecting abnormal perfusion changes in MCI and AD patients. The perfusion anomaly in group MCI and AD patients is closely related to changes in the structure and function of the brain. Third AMCI and mild AD based on voxel based whole brain DTI longitudinal study objective: To explore the change characteristics of white matter microstructure in aMCI and mild AD patients by magnetic resonance diffusion tensor imaging (DTI) technique. Methods: 3 MRI were used in 37 cases of aMCI, 30 mild AD and 30 normal elderly. Tract-basedspatial Statistics (TBSS) software based on fiber bundle to compare the difference of white matter structure in.17 cases, aMCI patients were followed up for one year. Results: compared with the normal control group, the right corpus callosum, bilateral inferior occipital fasciculus, upper longitudinal fasciculus, right inner capsule forelimb, anterior thalamus radiation and left longitudinal fasciculus were compared with the normal control group. The FA value of cerebral white matter decreased, most of the higher FA value was located in the right lateral corticospinal tract and anterior thalamus, followed by the right superior longitudinal fascicle, the cingulate bundle and the hippocampus, and the bilateral inferior occipital bundle, the right anterior thalamus, the right corpus callosum occipital and the left superior longitudinal bundle. The brain white matter MD area was mainly located in the left half of the hemisphere. The ball was concentrated on the left inferior longitudinal fasciculus, the hook shaped bundle, the lower occipital bundle, the upper longitudinal beam and the temporal and longitudinal fasciculus, the corticospinal tract, the right superior longitudinal fascicle, the upper longitudinal fascicle and the hook shaped bundle. The MD reduction area of the white matter was found in the small part of the right corticospinal tract. The difference was statistically significant (P0.05, t 2-6, Corrected). The left upper radiate crown of the mild AD group and the left upper longitudinal longitudinal section were in the mild AD group. Bundles, bilateral inferior occipital fasciculus, right cingulate hippocampal, outer capsule and dome, radiating in the left anterior thalamus, dome, terminal striate, outer capsule, and cingulate bundle of brain white matter FA value decreased; most of the FA increased area was located in the left corticospinal tract, anterior thalamus radiating, right superior longitudinal fascicles, also seen in the right hook bundle, cingulate bundle and hippocampus, inferior occipital fasciculus, right front Radiation of the thalamus, the occipital of the right corpus callosum radiation line, bilateral inferior longitudinal fasciculus, and the left cingulate bundle. The voxel in the MD area of the cerebral white matter increased obviously, mainly in the left hemisphere, concentrated in the left superior longitudinal tract, the corticospinal tract and the right corticospinal tract. The MD reduction area of the white matter was seen in the small part of the right corticospinal tract. The difference was statistically significant. Significance (P0.05, t value 2-6; Corrected). In longitudinal follow-up, the FA value of white matter decreased obviously, concentrated in the left upper and lower longitudinal fascicles, a little right cingulate bundle and the FA value of upper longitudinal bundle increased obviously, with the left occipital forceps and the right cingulate bundle mainly, and a little right cingulate bundle and the upper longitudinal bundle MD decreased. (P0.05, uncorrected, Cluster100 voxel). Conclusion: DTI can observe the changes in the microstructure of AD white matter. These changes can be a biological marker for diagnosis of disease. Fourth part aMCI and the resting state fMRI longitudinal study of mild AD: Combined Application of low frequency wave amplitude analysis (Amplitude of Low Frequency Fluctuation, ALFF) and seed point correlation analysis (seed-basedcorrelati) On analysis), to explore the change characteristics of resting state brain function connection in aMCI and mild AD patients. Methods: 3 magnetic resonance (MRI) was used to perform resting state fMRI scan in 37 cases of aMCI, 30 cases of mild AD and 30 normal old people. All data were pretreated with SPM8 software, and the amplitude analysis of low frequency wave was carried out by REST and DPARSF software. Compared with the normal group, the brain area was significantly different from that of the normal group, and the peak point of the brain area was extracted as the seed point. 4mm was used as the radius to do the whole brain function connection and the seed point was extracted for Pearson analysis. Results: compared with the normal control group, the higher ALFF area in the aMCI group was located in the right upper middle frontal gyrus, the lower ALFF area was located in the right frontal gyrus, and the left left anterior lobe was light. The increased area of ALFF in the AD group was located in the right corpus callosum, the left anterior motor cortex, the upper frontal gyrus, the lower ALFF area located in the right direct gyrus, the left cingulate gyrus, the posterior cingulate gyrus, and the anterior wedge of the wedge. Compared with the aMCI group, the mild AD was located in the right auxiliary movement area and frontal lobe, the left central anterior gyrus, paraclal lobule, cingulate gyrus. The auxiliary motor area is also seen in the right anterior central gyrus, the upper frontal gyrus, and the left posterior central gyrus, and the ALFF area is located in the bilateral cerebellum, the left inferior frontal gyrus, the upper occipital gyrus, the middle occipital gyrus (P0.01, uncorrected, K > 10 voxel), which is located in the anterior lobe of the wedge, the central cingulate gyrus, and the lower part of the right temporal lobe. The defaults in the AD group were located in the left Island lobe and the left inferior frontal gyrus, in the left frontal lobe, in the left inferior frontal gyrus, in the bilateral frontal lobe, in the middle temporal gyrus, and in the mild AD group compared with the aMCI group, and the area in the right upper frontal gyrus with the default network function, the lower area in the right frontal lobe, the anterior cingulate gyrus, the central cingulate gyrus, the temporal lobe, the upper margin, right frontal gyrus. The triangle, P0.01, uncorrected, voxel,.17 cases of aMCI cases were followed up one year later. The ALFF wave amplitude of right occipital lobe and cortex was decreased (P0.05, FWE corrected, K > 10 voxin); right cerebellum defaults, right apical lobule, angular gyrus, upper frontal gyrus, upper and lower lobule, inferior temporal gyrus, and middle frontal gyrus. Du Zenggao (P0.01, uncorrected, K > 10 voxin). Conclusion: the specific changes in the resting state brain function network can be found before the abnormal brain structure of mild AD patients through the seed point correlation analysis.

【学位授予单位】：复旦大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R445.2;R749.16

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