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学科主题: 影像医学与核医学
题名:
基于多模态磁共振成像在帕金森病的纵向研究
作者: 乔健
答辩日期: 2016-05-13
导师: 陈敏
专业: 影像医学与核医学
授予单位: 北京大学
授予地点: 北京大学第五临床医学院
学位: 博士
关键词: 帕金森病 ; 静息态磁共振 ; 纵向研究 ; 低频振幅 ; 功能连接
其他题名: Multimodal Magnetic Resonance Imaging Longitudinal Studies in Parkinson's Disease
分类号: R741.044
摘要:

第一部分 静息态功能磁共振成像在帕金森病的纵向研究

目的 应用静息态功能磁共振(Resting-state functional MRI rest-fMRI)技术,观察帕金森病(PD)患者脑功能两年以来的改变及与临床的相关性。

方法 选取24名明确诊断PD的患者,两年以来均规律服用抗帕金森药物。接受两次静息态功能磁共振扫描,前后间隔两年,分别作为基线组及随访组。所有MR扫描均使用荷兰菲利普公司3.0T磁共振成像系统,使用8 通道高分辨头颅磁共振线圈完成;并在扫描前完成患者受试者一般情况、利手调查、简易智能状态量表(MMSE)、Hoehn&Yahr病情分级表(H&Y)、同一帕金森病评定量表(UPDRS)的评估。扫描得到的静息态功能图像采用MR图像转换软件和基于Matlab2013平台的统计参数映射软件(SPM8)、静息态磁共振数据处理助手(DPARSF V2.0),对图像数据进行处理及分析。首先得到基线组与随访组两组患者的标准化脑功能低频振荡幅度mALFF统计图。结果利用静息态功能磁共振数据分析处理工具包(REST V1.8)进行如下统计分析:(1)采用配对样本t检验的方法,分析随访组与基线组mALFF统计图的差异;结果运用AlphaSim方法校正,以P<0.01,激活簇(cluster size)>77时,认为两组间有统计学差异。(2)采用相关性分析的方法,分别分析基线组及随访组mALFF值与患者UPDRS运动分的相关性,结果运用AlphaSim方法校正,以P<0.01,激活簇(cluster size)>46时,认为有统计学意义。之后选取手工选取以坐标(0,-44,28)为中心,5mm为半径的小球体作为种子点,得到种子点与其他脑区经过Z变化的功能连接值(zFC)。之后利用REST工具包,采用配对样本t检验的方法,分析随访组与基线组zFC统计图的差异;结果运用AlphaSim方法校正,以P<0.01,激活簇(cluster size)>16时,认为两组间有统计学差异。

结果 在P<0.01水平,与基线比较,随访组mALFF值显著减低的脑区有双侧小脑半球下部及小脑扁桃体、双侧背侧丘脑、右侧海马旁回、小脑山顶以及右侧岛叶皮层;随访组mALFF值显著增高的脑区有双侧额叶辅助运动区。基线组的mALFF值在左侧顶上小叶、枕叶皮层、右侧额上回、额中回区域与UPDRS运动分呈显著正相关;在右侧背侧丘脑、右侧海马旁回区域与UPDRS运动分呈显著负相关。随访组的mALFF值在右侧岛叶、双侧颞下回、双侧背侧丘脑、右侧中脑、右侧小脑中脚、双侧小脑半球上部、双侧直回、双侧额内侧回、右侧前扣带回、左侧额中回、双侧尾状核头、双侧壳核及苍白球区域与UPDRS运动分呈显著正相关;在左侧中央前回、中央后回、中央旁小叶、双层顶上小叶区域与UPDRS运动分呈显著负相关。在P<0.01水平,与基线比较,随访组在右侧小脑半球、右侧颞上回、双侧楔叶zFC值显著增高,在左侧额中回zFC值显著减低。

结论 PD的损害是广泛的,无论是运动功能损害或是认知功能损害,而且这些损害会随着PD病程的进展而改变,rest-fMRI或许能通过对各脑区功能改变的观察,来检测PD患者的病情变化。

 

第二部分 弥散张量成像在帕金森病的纵向研究

目的 应用弥散张量成像(DTI)技术,观察PD患者脑白质微结构两年以来的改变及与临床的相关性。

方法 选取24名明确诊断PD的患者,两年以来均规律服用抗帕金森药物。接受两次DTI序列磁共振扫描,前后间隔两年,分别作为基线组及随访组。所有MR扫描均使用荷兰菲利普公司3.0T磁共振成像系统,使用8 通道高分辨头颅磁共振线圈完成;并在扫描前完成患者受试者一般情况、利手调查、简易智能状态量表(MMSE)、Hoehn&Yahr病情分级表(H&Y)、同一帕金森病评定量表(UPDRS)的评估。结果运用虚拟机播放器VMware Player 6.0.1.以及基于Linux操作系统的图像转换软件(MRIcron所附带的dcm2niigui工具包)与牛津大学脑功能磁共振中心开发的FMRIB软件包(FSL 4.0),采用基于纤维束示踪的空间统计分析方法(TBSS),对图像数据进行处理和分析,生成每个受试者    FA骨架图。之后采用配对样本t检验的方法,观察随访组与基线组的FA骨架图的差异。记录基线组与随访组部分主要白质纤维束的FA值。结果利用SPSS 22.0软件,以配对样本t检验的方法观察两组间的差异性;再用线性回归的方法观察各主要白质纤维束FA值与H&Y分期、UPDRS运动分之间的相关性以及各主要白质纤维束FA变化值与H&Y分期、UPDRS运动分变化值之间的相关性,以P<0.05为有统计学意义。

结果 在P<0.05水平,与基线组比较,随访组在双侧放射冠、双侧上纵束、双侧钩束、双侧内囊前肢、双侧内囊后肢、双侧外囊、胼胝体体部、胼胝体压部、双侧大脑脚部位、双侧矢状层、双侧小脑半球及脑干等处白质纤维束FA值显著增高。在P<0.05水平,与基线组比较,随访组未发现任何区域白质纤维束FA值显著减低。各主要白质纤维束FA值与H&Y分期、UPDRS运动分之间以及各主要白质纤维束FA变化值与H&Y分期、UPDRS运动分变化值之间均无明显相关性(P<0.05)。

结论 PD患者存在广泛的微脑白质结构损害,规律抗PD治疗有缓解病程的效果,然而DTI研究能否成为PD病程的监测手段,还有待进一步研究。

 

英文摘要:

 

Part I  A resting-state functional MRI longitudinal study in Parkinson's disease

Objectives: Using resting-state functional MRI (rest-fMRI), we observed the alteration of brain function and its correlation with clinical scores in patients with parkinson’s disease

Methods: We totally chose 24 patients with clear diagnosis of PD, who took anti-Parkinson's disease drugs regularly during the past two years. They received twice rest-fMRI scannings with an interval of two years, as a baseline and a follow-up group respectively. All subjects were scaned with Dutch Philips 3.0 T magnetic resonance imaging system, using an 8 channel high resolution head MRI coil. We evaluated the general conditions, the handedness survey ,Mini-mental state examination(MMSE),  Hoehn&Yahr disease classification scale(H&Y)and Unified Parkinson's Disease Rating Scale(UPDRS) of all subjects before the MRI scan. The fMRI data were processed and analysed by DPARSF V2.0 soft and REST V1.8 soft. Firstly, we got the mALFF statistical figure of baseline group and follow-up group. We used the REST V1.8 soft to analyse the results as follows: (1)Analysed the difference of the mALFF statistical figure of baseline group and follow-up group with pared-samples T test. The results were corrected with the AlphaSim text method. there was a statistical significance when P<0.01 and the cluster size > 77. (2) Analysed the correlation between the mALFF of baseline group and follow-up group and the UPDRS motor scores with the correlation analysis method . The results were corrected with the AlphaSim text method. there was a statistical significance when P<0.01 and the cluster size > 46.Then we chose a seed point manually with a coordinate of (0,-44,28) and a radius of 5mm, and got the Function connection values between the seed piont and other encephalic region after a Z transform(zFC).We analysed the difference of the zFC statistical figure of baseline group and follow-up group with pared-samples T test. The results were corrected with the AlphaSim text method. there was a statistical significance when P<0.01 and the cluster size >16.

Results: At P<0.01 level we found that comparing with baseline group, the following group's mALFF decreased significantly in the brain area of lower part of bilateral cerebellar hemisphere and amygdala, bilateral dorsal thalamus, the right parahippocampal gyrus, mountain top of the cerebellum, and the right side of the island to cortex. the following group's mALFF increased significantly in the brain area of bilateral frontal supplementary motor area. The baseline group's mALFF had a significant positive correlation with UPDRS motor scores in the brain area of the left superior parietal lobule, the occipital cortex, the right superior frontal gyrus, and the right dle frontal gyrus; and a significant negative correlation in the brain area of the right dorsal thalamus and the right parahippocampal gyrus. The following group's mALFF had a significant positive correlation with UPDRS motor scores in the brain area of the right insularlobe cortex, the bilateral anteromedial temporal gyrus, the bilateral dorsal thalamus, the right brain, the right dle cerebellar peduncle, the bilateral upper cerebellar hemisphere, the bilateral straight gyrus, the bilateral medial frontal gyrus, the right anterior cingutate, the left dle frontal gyrus, the bilateral caudate nucleus head and the bilateral putamen; and a significant negative correlation in the brain area of the left precentral gyrus ,the postcentral gyrus, the paracentral lobule and the bilateral superior parietal lobule. At P<0.01 level, we found that comparing with baseline group, the following group's zFC decreased significantly in the brain area of the right cerebellar hemisphere, the right superior temporal gyrus, the bilateral cuneus, the following group's zFC increased significantly in the brain area of the left dle frontal gyrus.

Conclusion: PD’s damage is extensive, whether movement damage or cognitive impairment, and the damage and subject to change with the progress of the PD duration, Rest - fMRI may detect PD patient's condition changes through the observation of the various brain regions function change.

 

Part II  A diffusion tensor MRI longitudinal study in Parkinson's disease

Objectives: Using diffusion tensor MRI (DTI), we observed The alteration of brain function and its correlation with clinical scores in patients with parkinson’s disease.

Methods: We totally chose 24 patients with clear diagnosis of PD, who took anti-Parkinson's disease drugs regularly during the past two years. They received twice DTI scannings with an interval of two years, as a baseline and a follow-up group respectively. All subjects were scaned with Dutch Philips to 3.0 T magnetic resonance imaging system, using an 8 channel high resolution head MRI coil. We evaluated the general conditions, the handedness survey ,Mini-mental state examination (MMSE),  Hoehn&Yahrdisease classification scale(H&Y)and Unified Parkinson's Disease Rating Scale(UPDRS) of all subjects before the MRI scan. The DTI data were processed and analysed by VMware Player 6.0.1.and FMRIB software library 4.0(FSL 4.0),using Tract Based Spatial Statistics (TBSS) method to generate all subject's FA skeleton graph. Then we used the pared-samples T test to observe the FA skeleton graph differences between the baseline and follow-up group. We recorded the baseline and follow-up group of main white matter fiber tracts of FA value. Then we used the SPSS 22.0 soft to analysis the FA value differences between the baseline and follow-up group with the method of pared-samples T test. And we observed the correlation between the FA value of main white matter fiber and the H&Y、UPDRS motor score, then the change value between them , with P < 0.05 for statistical significance .

Results: At P<0.05 level we found that comparing with baseline group, the following group's FA increased significantly in bilateral corona radiata, bilateral superior longitudinal fasciculus, bilateral uncinate faciculus, bilateral anterior limb of internal capsule, bilateral posterior limb of internal capsule, bilateral external capsule, bilateral sagittal layer, bilateral cerebral peduncles, bilateral cerebellar hemispheres and the brainstem; We didn't find any fiber's FA decrease. There is neither significant correlation between the FA value of main white matter fiber and the H&Y、UPDRS motor score, nor the change value between them(P<0.05).

Conclusion: PD patients have widespread microbrain white matter structure damage, regular treatment against PD can alleviate the effect of the course. However, whether DTI research can be PD monitoring means of course, remains to be further researched.

 

语种: 中文
相关网址: 查看原文
内容类型: 学位论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/124789
Appears in Collections:北京大学第五临床医学院_学位论文

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作者单位: 北京大学第五临床医学院

Recommended Citation:
乔健. 基于多模态磁共振成像在帕金森病的纵向研究[D]. 北京大学第五临床医学院. 北京大学. 2016.
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