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扩散磁共振成像的方法及其在精神分裂症中的应用研究
谢桑马
学位类型工学博士
导师蒋田仔
2016-11-30
学位授予单位中国科学院大学
学位授予地点北京
关键词扩散磁共振成像 高角分辨率扩散成像 B值 精神分裂症 言语性幻听 高危 脑结构连接 脑结构网络
摘要      扩散磁共振成像是一种无创检测大脑白质纤维结构的成像技术。它可以通过探测组织中水分子的扩散情况来推测神经微观组织信息,刻画脑白质纤维形态学信息,从而获取脑结构连接信息。扩散磁共振成像经常被用于脑结构连接和脑结构网络的研究中。在扩散磁共振成像中主要有两类刻画水分子扩散分布函数的模型,分别是扩散张量成像和高角分辨率扩散成像。精神分裂症是一种常见的较为严重的精神疾病。许多研究表明精神分裂症是一种失连接症,即精神分裂症的症状及表现并不是源于单一脑区的病理改变,而是由于多个脑区交互作用发生了异常。因此,扩散磁共振成像是研究精神分裂症患者的脑连接和脑网络的重要工具。在本论文中,本人集中于扩散磁共振成像的计算方法和分析工具研究及其在精神分裂症上的临床应用。在计算方法和分析工具方面,我们研究了b值参数对临床高角分辨率扩散成像中水分子扩散估计的影响,还开发了一套一体化的扩散磁共振成像数据分析软件。在临床应用研究中,我们基于扩散磁共振成像数据研究了精神分裂症言语性幻听患者的脑结构连接以及精神分裂症高危人群的脑结构网络。本文的主要内容和贡献如下:
  1. 利用多b值高角分辨率扩散成像数据提出了在临床研究中的合适b值参数。为了保证高质量的估计,高角分辨率扩散成像对b值的要求比较高。在3.0T的磁共振机器上采集了人脑的多个b值(650,1000,1500,2000和2500 s/mm2)的高角分辨率扩散成像数据。使用球极傅里叶成像方法和约束球反卷积方法分别估计了dODF和fODF。利用ODF的半高全宽指标和不同b值下ODF主方向的角度差来定量评估ODF估计质量,发现b值在2000 s/mm2和2500 s/mm2时半高全宽没有显著差异,同时b值达到2000 s/mm2左右时ODF主方向开始保持稳定。同时通过观察复杂区域的ODF估计质量评估最优b值,发现b值≥2000 s/mm2时两种方法基本可以解决多纤维交叉问题。综合信噪比和采集时长等因素,我们认为b = 2000 s/mm2是目前HARDI方法应用于临床研究时估计dODF和fODF的合适选择。
  2. 开发了一套一体化的扩散磁共振成像数据分析软件DiffusionKit。为了利用扩散磁共振成像数据进行脑网络研究,研究人员开发了多个数据分析软件。而目前现有的软件存在一些自身的限制。基于C/C++语言,利用Qt和VTK开发了一套轻量化一体式的扩散磁共振成像数据分析软件。该软件包含了数据格式转换、数据预处理、水分子扩散函数估计、纤维跟踪、网络构建和多样可视化功能。DiffusionKit为基于dMRI的研究提供了一站式的解决方案,为不同背景的研究人员提供了高效的分析工具。
  3. 基于多中心数据,发现了精神分裂症言语性幻听患者中稳定的异常连接模式。言语性幻听是精神分裂症中主要的症状之一。有研究表明连接Broca区和Wernicke区的弓状束和跨半球听觉通路在言语性幻听患者中表现异常,但这些报道的异常模式不一致。在本研究中,利用多中心大样本的扩散磁共振成像数据,研究健康被试、非言语性幻听患者和言语性幻听患者在左侧弓状束和跨半球听觉通路上的影像学指标。我们发现言语性幻听患者在左侧弓状束上的FA值要显著高于健康被试,非言语性患者处于中间,但不具有显著性。在跨半球听觉通路上,非言语性患者的MD值要显著高于健康被试,而言语性幻听患者处于中间,但不具有显著性。研究结果不仅支持言语性幻听中自我监控异常和听觉皮层异常的两种假说,同时还得到了相关纤维束稳定可重复的异常模式。
      利用扩散磁共振成像数据研究精神分裂症及其高危人群的脑连接和脑网络,发现了异常的连接模式和网络拓扑属性。在脑结构连接分析中,我们利用ICBM-DTI-81的白质纤维束图谱对健康被试、精神分裂症患者和高危人群的48条主要纤维束进行脑结构连接分析。发现穹窿、右侧扣带和右侧前放射冠这三条纤维的FA值和MD值都存在显著的组间差异。在穹窿和右侧扣带上,精神分裂症被试和健康被试存在显著的差异,而高危人群处于两组之间,但没有显著性差异。在脑结构网络分析中,利用AAL模板中的脑区作为网络的节点,脑区间的纤维连接数目作为边构建网络。发现全局效率和局部效率在三组之间存在显著的差异,精神分裂症被试的这两个指标都要显著低于健康被试,而高危人群的这两个属性在两组之间,但没有显著性。我们的发现不仅支持精神分裂症是与遗传因素高度相关的精神疾病这一结论,同时为精神分裂症的早期诊断和治疗提供帮助。
其他摘要      Diffusion MRI (dMRI) is a non-invasive imaging technique, which can be utilized to reveal the microstructure of the white matter of the in-vivo human brain. Diffusion MRI is widely used in the studies of brain structural connectivity and structural network because it can explore the information of neural micro-structure by probing the diffusion of water molecules. There are two major types for characterizing the diffusion of water molecules. One is diffusion tensor imaging (DTI) and the other is high angular resolution diffusion imaging (HARDI). Schizophrenia (SZ) is a psychiatric disorder and many studies indicated that it may result from the improper functional and structural connectivity among brain regions. In this dissertation, we focus on the methodology of diffusion MRI and its applications in schizophrenia. We firstly studied the effect of b-value in HARDI reconstruction using clinical dMRI data. Then we developed a light, one-stop, cross-platform solution for dMRI data analysis, called DiffusionKit. In the part of applications in schizophrenia, we studied the structural connectivity in schizophrenia patients with auditory verbal hallucination (AVH) and the structural network in schizophrenia high-risk individuals. The main contents and contributions of the dissertation are as follows:
  1. We proposed the optimal b-value in HARDI reconstruction for clinical studies. Diffusion MRI data with various b-values (650, 1000, 1500, 2000 and 2500 s/mm2) were collected on a GE 3T MRI scanner. To reconstruct the diffusion ODF and fiber ODF, spherical polar fourier imaging and constrained spherical deconvolution approaches were applied separately. The full width at half maximum (FWHM) of the ODF and the angular difference of the peaks extracted from ODF were measured to investigate the effect of b-value on the ODF reconstruction. The differences in the FWHM for the diffusion ODF and the fiber ODF between the b-values of 2000 s/mm2 and 2500 s/mm2 were not significant. The angular differences of the ODF between 2000 s/mm2 and 2500 s/mm2 were lowest in both single-directional and two-directional situations. Visual inspection of the ODF was used to evaluate the reconstructions. b = 2000 s/mm2 and above revealed most of the two-way or three-way crossing-fiber structures. Considering both the signal-to-noise ratio and the acquisition time, b = 2000 s/mm2 is the basic requirement for ODF reconstruction using current HARDI methods on clinical data.
  2. We developed a light, one-stop, cross-platform solution for dMRI data analysis, called DiffusionKit. Different groups developed various tools for studies of brain network. However, the existing toolkits for dMRI analysis have some limitations. The DiffusionKit package is implemented in C/C++ and Qt/VTK. It includes data format conversion, dMRI preprocessing, local reconstruction, white matter fiber tracking, fiber statistical analyses and various visualization schemes. The rich functions for both data analysis and visualization will facilitate and benefit dMRI research.
  3. We found reproducible abnormal pattern of specific tracts in schizophrenia with auditory verbal hallucination (AVH) base on multi-site diffusion MRI data. AVH is one of the primary symptoms of schizophrenia. Previous diffusion MRI studies have proposed considerable heterogeneity in the abnormal patterns of left arcuate fasciculus (AF) and interhemispheric auditory connectivity. In this study, we investigated the left AF and interhemispheric auditory connectivity in healthy controls (HC), non-AVH and AVH using relative large sample collected from multiple sites. AVH showed significantly increased FA in AF compared with HC. The non-AVH group showed intermediate FA value, and did not differ significantly from either group. We found a significant increase of MD in the interhemispheric auditory connectivity in the non-AVH group compared to the HC group. The AVH group showed intermediate FA value, and did not differ significantly from either group. Our findings not only supported the hypothesis of self-monitoring account and spontaneous activation account, but also reveled consistent abnormal pattern.
      We used diffusion MRI to study the connectivity and network in schizophrenia (SZ) high-risk (HR) individuals and found abnormal connecting patterns and topological properties. We applied the ICBM-DTI-81 white matter atlas to study the 48 tracts in HC, SZ and HR. And found a significant group difference of FA and MD values in the fornix, right cingulum and right anterior corona radiate. There was a significant difference between SZ and HC in fornix and right cingulum. HR showed intermediate value, and did not differ significantly from either group. In the analysis of brain network, we utilized the AAL template to segment the brain into 90 brain regions which acted as nodes in the network. And the number of fibers between regions is the edge of the network. We found a significant group difference in global efficiency and local efficiency. SZ group showed decreased efficiency compared to HC. HR showed intermediate value, and did not differ significantly from either group. Our findings ont only supported the relationship between schizophrenia and the genetic factor, but also provided help in early diagnosis and treatment of schizophrenia.
语种中文
文献类型学位论文
条目标识符http://ir.ia.ac.cn/handle/173211/12787
专题毕业生_博士学位论文
作者单位中国科学院自动化研究所
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谢桑马. 扩散磁共振成像的方法及其在精神分裂症中的应用研究[D]. 北京. 中国科学院大学,2016.
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