青光眼是世界上的第二大致盲疾病，近些年其研究得到越来越多的关注。本文使用包括T1加权像、静息态功能磁共振成像（functional Magnetic Resonance Imaging, fMRI）在内的多模态医学影像技术从脑结构、脑功能和脑网络三个层面来研究原发性开角型青光眼患者脑的改变，研究内容具有重要的理论意义和临床价值。本文主要研究内容及创新点如下： （1）本文提出了一个基于T1加权像的外侧膝状体（Lateral Geniculate Nucleus, LGN）的全自动分割算法。在该算法中，我们首先自动分割出腹侧间脑作为LGN的先验限制，然后在该区域中采用种子生长法自动分割出LGN。实验结果验证了LGN分割方法的正确性。另外，我们发现正常人LGN的体积存在偏侧性（左侧大于右侧），而且会随着年龄的增大而减小。我们还将其应用于青光眼的研究中，发现青光眼患者的LGN体积减小，且患者LGN体积和临床参数存在相关性。 （2）本文提出了结合了体积、表面和感兴趣区三种形态学分析来研究青光眼患者脑结构变化的研究方案。在基于体积的形态学分析中，我们采用VBM （Voxel-based Morphometry）方法发现患者不存在灰质体积发生显著改变的脑区域。在基于表面的形态学分析中, 我们发现患者右侧额极的皮层厚度显著性减小。在基于感兴趣区分析中，我们发现双侧LGN、右侧V1和左侧杏仁核体积萎缩，右侧V1的皮层厚度变薄。此外，我们还发现双侧LGN体积和右侧V1的皮层厚度都和临床参数有着显著的相关性。这些结果表明青光眼患者脑结构发生了可塑性重组，而且重组的区域不局限于视觉相关脑结构。 （3）本文同时采用低频振荡振幅（Amplitude of Low Frequency Fluctuation，ALFF）、比率低频振荡振幅（fractional ALFF，fALFF）和局部一致性（Regional Homogeneity， ReHo）来研究青光眼患者脑功能发生的改变。我们发现青光眼患者双侧枕极的ALFF显著性减弱，左侧楔皮层、右侧梭状回和右侧枕极的fALFF显著减弱，左侧颞极的fALFF显著增强，双侧枕极和左侧舌回的ReHo值显著减小。这些结果证实了青光眼患者的视觉皮层的功能发生变化，也说明青光眼不仅仅是一个眼部的疾病，还涉及到脑部功能的病变。 （4）本文采用图论方法从全局和局部两个层面研究青光眼患者全脑功能网络的变化。结果发现青光眼患者全脑网络的全局属性没有显著变化，但所有局部属性均发生了变化。进一步的核心节点分析发现，与正常人相比，青光眼患者脑网络丢失了6个核心节点，出现了9个新的核心节点，且其中两个核心节点（右侧梭状回，右侧舌回）的介数中心度和视野之间存在相关性。这些均反映了青光眼患者脑网络的重塑。这些均反映了青光眼患者脑网络的重塑，而且右侧梭状回和右侧舌回这两个核心节点的介数中心度可以作为衡量青光眼严重程度的生物标记。 （5）本文研究了青光眼患者视觉网络和默认网络这两个子网络的变化。我们利用组独立成分分析算法从静息态fMRI数据中分出视觉网络和默认网络，然后对其分别进行功能连接分析和功能网络连接分析。功能连接分析发现青光眼患者视觉网络中枕极的功能连接下降；功能网络连接分析发现视觉网络内部网络成分彼此之间的连接均...
英文摘要
Glaucoma is the second leading cause of blindness and has been the topic of intense study to uncover the underlying mechanisms of the disease. In this dissertation, we applied multi-modal imaging including T1-weighted imaging and resting-state fMRI to investigate the alterations of brain structure, function and network in primary open angle glaucoma (POAG) patients. The contents and contributions of this dissertation are as follows： (1) We proposed an automatic lateral geniculate nucleus (LGN) segmentation algorithm based on T1-weighted imaging. First, we used the prior information of LGN, i.e. LGN is a part of ventral diencephalon area (VDC), to create a prior mask. Then we applied region growing with radius 5mm to delineate LGN. The experiment results proved the validity of the segmentation algorithm. In addition, we found LGN asymmetry as well as LGN atrophy along with age in the normal controls. We also applied the automatic LGN segmentation to investigate glaucoma effects on LGN volumes and found that the bilateral LGN volumes became smaller in glaucoma patients and the LGN volumes were correlated with clinical parameters in patients. (2) We investigated brain structural changes comprehensively in POAG patients by three independent measurements: volume-based analysis (VBA), surface-based analysis (SBA) and ROI-based analysis. VBA showed no significant differences in gray matter volumes between two groups. SBA revealed significantly reduced cortical thickness in the right frontal pole, and ROI-based analysis showed volume shrinkage in bilateral LGN, right V1 (caused by reduced right V1 thickness) and left amygdala. Moreover, the bilateral LGN volumes and the right V1 thickness were correlated with clinical parameters in glaucoma. These results demonstrate that structures alterations not only affect vision-related structures but also other cortical regions in POAG patients. (3) We investigated brain functional changes comprehensively in POAG patients by the analysis of ALFF (Amplitude of Low Frequency Fluctuation), fALFF (fractional ALFF) and ReHo (Regional Homogeneity). ALFF analysis showed lower ALFF in the bilateral occipital pole in patients. fALFF analysis showd lower fALFF in the left cuneus, the right fusiform gyrus and the right occipital pole and higher fALFF in the left temporal pole. ReHo analysis showed lower ReHo in the bilateral occipital pole and the left lingual gyrus. These results prove the functional alterations of the visual c...
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