原发性开角型青光眼中枢形态学及功能学改变的MRI研究

发布时间：2018-04-22 16:49

本文选题：外侧膝状体 + 原发性开角型青光眼　；参考：《华中科技大学》2012年博士论文

【摘要】：青光眼是世界上第一位不可逆性致盲眼病,是一组以进行性视网膜神经节细胞及其轴突的丢失为特征的视神经病变。已有研究证实原发性开角型青光眼神经损伤不仅仅局限于眼部,而且累及全视路。目前该疾病中枢损害的研究数据多来自动物实验。磁共振成像技术具有无创、可重复、高的时间和空间分辨率等特点,已被广泛应用于脑神经科学的基础研究和临床应用中,为在体研究原发性开角型青光眼脑损害机制提供有效手段。本研究主要利用3.0T高分辨力磁共振成像技术,从形态学及功能学相结合的角度,探讨原发性开角型青光眼患者外侧膝状体形态变化、中枢视路神经纤维改变及静息态脑功能变化的特点。第一部分原发性开角型青光眼的外侧膝状体形态学改变目的：观察原发性开角型青光眼(Primary open-angle glaucoma, POAG)患者外侧膝状体(Lateral geniculate nucleus, LGN)最大高径及体积的变化,并分析与视神经及视功能损害的相关性特点。方法：选取25名POAG患者(男19例,女6例,21-54岁)及与之年龄性别匹配的正常人24例(男19例,女5例,21-55岁),经青光眼专科检查采集眼部临床数据：如视盘分析(Cup-to-disc ratio, CDR)、视网膜神经纤维层厚度分析(Retinal nerve fiber layer thickness, RNFLT)、视野检查(Mean sensitivity,MS和Mean defect, MD*)等,使用3.0T GE磁共振扫描仪,所有受试者采用3D-BRAVO及Proton density序列完成LGN扫描,使用Advantage work-station软件测量双侧LGN的最大高径及体积,对比两组之间的LGN形态学差异,并分析与视神经CDR、RNFLT及视野检查MS、MD*的相关性。结果：POAG组双侧LGN最大高径(右侧4.36±0.62mm,左侧4.32±0.62mm)及体积(右侧97.48±27.61mm3,左侧92.68±25.79mm3)小于正常对照组(5.02±0.42mm,4.99±0.411mm及143.46±22.81 mm3,142.88±20.47 mm3)(p0.001)。POAG患者LGN最大高径及体积与眼部视神经的CDR呈负相关,与RNFLT呈正相关,与视野检查的MS值呈正相关,与MD*值呈负相关(p0.05)。正常人LGN最大高径及体积与年龄无显著相关性,与眼部视神经的CDR及RNFLT无显著相关性(p0.05)。结论：POAG神经损伤跨突触累及双侧LGN,且其萎缩与眼部视神经损伤及视功能缺损显著相关。本研究中所开展的LGN最大高径及体积测量,可用以研究POAG中枢损伤,并为视神经及视功能损害程度的临床诊断评估提供客观指标。第二部分POAG患者的中枢视路神经纤维改变目的：观察POAG患者中枢视路神经纤维改变的部位及性质,并分析与视神经、视功能损害及LGN形态变化的相关性。方法：入组的25例POAG患者及24例正常人,所有受试者接受3.0T GE磁共振扫描仪完成全脑弥散张量成像(Diffusion tensor imaging, DTI)扫描,使用FMRIB's Diffusion Toolbox软件,采用基于神经束空间统计学(Tract-based spatial statistics, TBSS)的DTI数据分析方法,分析出两组之间中枢视路神经纤维弥散特性有差异的部位,计算出差异部位的弥散参数各向异性分数(Fractional anisotropy, FA)及平均弥散值(Mean diffusivity, MD),并分析与视神经CDR、RNFLT及视野检查MS、MD*值及LGN形态学的相关性。结果：POAG组双侧视束及视放射神经纤维弥散特性与正常组存在显著差异,表现为FA值降低,MD值升高(p0.05)。POAG组中,患者视束及视放射FA值与CDR、RNFLT、视野检查的MS及MD*有显著相关性(p0.05)；视束MD值与视神经及视功能损害有相关性(p0.05),且与视神经损伤相关性更好；而视放射MD值与视神经及视功能损害均无相关性(p0.05)。POAG患者视束及视放射FA值与LGN最大高径及体积呈显著正相关(p0.05),MD值与其无相关性(p0.05)。与所匹配正常人对比,POAG患者视束FA及MD值的改变要大于视放射(p0.05)。正常组双侧视束及视放射神经纤维弥散特性(FA值及MD值)与年龄无显著相关性(p0.05)。结论：POAG患者视束及视放射神经纤维的损伤,与眼部视神经、视功能损伤及LGN形态改变显著相关,FA值与其相关性更好；且视束损伤较视放射腰严重。本研究所使用TBSS-DTI方法中FA值值可用于有效定量分析POAG中枢视路神经纤维损伤。第三部分POAG患者的静息态脑功能变化目的：探讨POAG患者静息态脑功能活动与正常人之间的差异。方法：入组的25例POAG患者及24例正常人,均经3.0T GE磁共振扫描仪,完成全脑静息态功能磁共振扫描,使用REST软件及局部一致性(Regional homogeneity, ReHo)的分析方法,分析出两组之间静息态脑功能活动有统计学差异的脑区。结果：与正常对照组相比,POAG患者的双侧枕叶、额下回、右侧颞叶静息态脑活动的ReHo值降低(p0.05)；双侧背侧丘脑、额上回、脑桥背部、梭状回静息态脑活动ReHo值增高(p0.05)。结论：POAG患者多个脑区静息态脑功能活动表现异常,这种多脑区的功能紊乱可能参与POAG的发病。
[Abstract]:Glaucoma is the first irreversible blindness eye disease in the world. It is a group of optic neuropathy characterized by the loss of progressive retinal ganglion cells and their axons. It has been proved that the primary open angle glaucoma is not limited to the eye, but is involved in the whole optic pathway. From animal experiments, magnetic resonance imaging (MRI), which has the characteristics of noninvasive, repeatable, high time and spatial resolution, has been widely used in the basic research and clinical application of brain neuroscience, and provides an effective hand to study the mechanism of brain damage in primary open angle glaucoma in vivo.
In this study, 3.0T high resolution magnetic resonance imaging (fMRI) was used to investigate the morphological changes of the lateral geniculate body, the changes of the central optic nerve fibers and the changes of resting state brain function in the patients with primary open angle glaucoma.
Part one
Morphological changes of lateral geniculate body in primary open angle glaucoma
Objective: To observe the maximum height and volume changes of the lateral geniculate body (Lateral geniculate nucleus, LGN) in patients with Primary open-angle glaucoma (POAG), and to analyze the correlation with optic nerve and visual impairment.
Methods: 25 POAG patients (19 men, 6 women, 21-54 years old) and 24 normal persons with age and sex (19 men, 5 women, 21-55 years old) were collected by glaucoma specialist examination, such as Cup-to-disc ratio (CDR), retinal nerve fiber layer thickness analysis (Retinal nerve fiber layer thickness, RNFLT). Mean sensitivity, MS and Mean defect, MD*, etc., using the 3.0T GE MRI scanner, all subjects completed LGN scans using 3D-BRAVO and Proton density sequences, and measured the maximum diameter and volume of both sides. FLT and field of vision check the correlation between MS and MD*.
Results: the maximum diameter of LGN in POAG group (4.36 + 0.62mm, left 4.32 + 0.62mm) and volume (right 97.48 + 27.61mm3, left 92.68 + 25.79mm3) were less than that of normal control group (5.02 + 0.42mm, 4.99 + 0.411mm and 143.46 + 22.81 mm3142.88 + 20.47 mm3) (p0.001). There was a positive correlation with RNFLT, positive correlation with MS value of visual field examination and negative correlation with MD* value (P0.05). There was no significant correlation between the maximum height and volume of LGN in normal people, and no significant correlation with CDR and RNFLT in the ocular optic nerve (P0.05).
Conclusion: POAG nerve injury is involved in bilateral LGN, and its atrophy is significantly related to ocular optic nerve injury and visual impairment. The maximum diameter and volume measurement of LGN in this study can be used to study the damage of the POAG center and provide an objective index for the diagnosis and evaluation of the optic nerve and the degree of visual impairment.
The second part is the change of central optic nerve fibers in POAG patients.
Objective: To observe the location and nature of central optic nerve fiber changes in POAG patients, and analyze the correlation with optic nerve, visual function damage and LGN morphological changes.
Methods: 25 patients with POAG and 24 normal subjects were enrolled in the study. All subjects received 3.0T GE MRI scanner to complete the whole brain diffusion tensor imaging (Diffusion tensor imaging, DTI) scan. The FMRIB's Diffusion Toolbox software was used, and the data analysis side based on the spatial statistics of neuro beam spatial statistics (Tract-based spatial) was used. The method was to analyze the parts of the two groups with difference in the dispersion characteristics of the central optic nerve fibers, and calculate the anisotropic fraction (Fractional anisotropy, FA) and the average dispersion (Mean diffusivity, MD) of the different parts of the optic nerve, and analyze the correlation with the MS, MD* value and LGN morphology of the optic nerve CDR, RNFLT and the visual field.
Results: the dispersion characteristics of bilateral optic tract and optic nerve fiber in the POAG group were significantly different from those in the normal group, which showed that the FA value decreased and the MD value increased (P0.05) in the.POAG group. The visual tract and the FA value of the optic radiation had significant correlation with CDR, RNFLT, MS and MD* in the visual field examination (P0.05); the optic tract MD value was related to the optic and visual impairment. The correlation between optic nerve and optic nerve damage was better, but the MD values of optic and optic nerve and visual impairment were not correlated with the optic nerve and visual function (P0.05).POAG patient's optic tract and the FA value with the maximum height and volume of LGN (P0.05), MD value and no correlation (P0.05). Compared with the matched normal person, the changes of FA and MD in the optic tract of the patients were greater than that of the matched normal people. Visual radiation (P0.05). The diffusion characteristics of bilateral optic tract and optic nerve fibers in normal group (FA value and MD value) were not significantly correlated with age (P0.05).
Conclusion: the damage of optic tract and optic nerve fiber in POAG patients is significantly related to ocular optic nerve, visual impairment and LGN morphologic changes. The value of FA is better and the optic tract injury is more severe than that of the radiation waist. The value of FA in this study can be used to quantitatively analyze the damage of the optic nerve fibers in the POAG center.
The resting state brain function changes in the third part of POAG patients
Objective: To explore the difference between resting state brain function and normal subjects in POAG patients.
Methods: 25 POAG patients and 24 normal people were treated with 3.0T GE MRI scanner to complete the whole brain resting state functional magnetic resonance imaging (fMRI). Using REST software and local conformance (Regional homogeneity, ReHo) analysis method, the brain areas with resting state brain work between two groups were statistically different.
Results: compared with the normal control group, the ReHo value of the bilateral occipital lobes, the lower frontal gyrus and the resting state of the right temporal lobe in the POAG patients decreased (P0.05), and the ReHo value of the bilateral dorsal thalamus, the upper frontal gyrus, the pontine back, the spindle gyrus and the resting state of the resting state increased (P0.05).
Conclusion: there are abnormal resting state brain function in multiple brain regions of POAG patients, which may be involved in the pathogenesis of POAG.

【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R775

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