原发性闭角型青光眼患者丘脑—皮质通路功能连接及脑网络拓扑属性的静息态fMRI研究
发布时间：2018-10-29 18:08
【摘要】：目的:采用基于种子点的功能连接(functional connectivity,FC)和以图论(graph theory)方法,分析原发性闭角型青光眼(primary angle-closure glaucoma,PACG)患者静息态下丘脑-皮层通路功能连接及脑网络拓扑属性的改变,以期提高对PACG患者可能的神经机理的认识,为临床早期诊断和治疗提供帮助。方法:招募33例PACG患者(PACG组)与33例年龄、性别相匹配的健康对照者(healthy controls,HC组),所有PACG患者均行相应的眼科检查,包括视网膜神经纤维层(retinal nerve fiber layer,RNFL)厚度、眼内压(intraocular pressure,IOP)、静脉杯盘比(cup to disc ratio,CDR)及视力(visual activity,VA)。所有受试者均行SIEMENS Trio Tim 3.0T MR扫描仪扫描,得到静息态功能磁共振图像(resting-state functional MRI,RS-fMRI)。数据处理主要分为:(1)采集静息态数据;(2)使用DPARSFA软件包进行数据预处理;(3)选取双侧丘脑的各7个亚区作为感兴趣区(region of interest,ROI),并以此为种子点与全脑各体素进行功能连接分析,并进行组间两独立样本t检验(AlphaSim矫正,P0.01);(4)应用Gretna脑网络分析软件包,选择116个自动解剖标定(automated anatomical labeling,AAL)模板脑区为节点,计算功能连接后获得矩阵,构建二值化脑网络,获取脑网络整体及局部属性,并在局部属性上行组间双样本t检验(错误发现率矫正(false discovery rate,FDR),P0.05);(5)分析差异脑区的相关系数值及网络属性值,使用SPSS v.17.0软件,对其与临床参数RNFLT,静脉CDR,IOP及VA进行Pearson相关性分析。结果:(1)与HC组比较,PACG组丘脑与视觉传导通路(顶叶/楔前叶、额叶/额下回)及非视觉传导通路(中央旁小叶、中央后回、边缘叶/海马旁回)功能连接减低,丘脑与视觉传导通路(枕叶、顶叶/顶下小叶、颞叶/颞下回)以及非视觉传导通路(小脑前叶/山顶)功能连接增加(P0.01,AlphaSim校正,簇≥29体素)。(2)在网络稀疏度(0.1~0.6)下,PACG及HC组脑网络标准化聚类系数(γ)㧐1,标准化最短路径长度(λ)≈1,且其小世界指数(σ)㧐1,两组均具有“小世界”属性。(3)在最小及最大网络稀疏度(0.32~0.42)下,与HC组比较,PACG组标准化聚类系数(γ)轻度减低(P:0.283~0.453),标准化最短路径长度(λ)无变化(P:0.463~0.993),导致小世界指数(σ)轻度减低(P:0.322~0.548),但上述差异均无统计学意义(FDR矫正,P0.05)。PACG组全脑(E_(global))及局部(E_(local))效应亦无明显变化(FDR矫正,P0.05)。(4)在最小网络稀疏度(0.32)下,与HC组比较,PACG患者组初高级视觉皮层(双侧距状裂周围皮层、左侧枕上回、右侧枕下回、双侧楔叶)标准化节点度显著降低,背侧视觉通路(右侧丘脑、双侧颞中回)及非视觉通路(双侧补充运动区、右侧海马旁回、右侧中央旁小叶、右侧岛盖部额下回)标准化节点度显著增高(FDR矫正,P0.05);背侧视觉通路(左侧枕上/下回、双侧楔叶、左侧舌回)及非视觉通路(左背外侧额上回、左侧眶部额上/中回、左侧海马、左侧豆状壳核、左侧小脑半球、小脑蚓部)标准化节点介数减少,背腹侧视觉通路(右侧颞中回、左侧颞下回)及非视觉通路(右侧海马旁回、右侧中央旁小叶、双侧岛盖部额下回、双侧缘上回)标准化节点介数显著增加(FDR矫正,P0.05)。(5)在最小网络稀疏度(0.32)下,PACG组左侧眶部额中回标准化节点介数与静脉CDR呈正相关(r=0.406,P=0.019)。PACG组左侧缘上回标准化节点介数与VA呈正相关(r=0.357,P=0.041);右侧缘上回标准化节点介数与VA呈明显正相关(r=0.558,P=0.001);左侧豆状核标准化节点介数与VA呈正相关(r=0.355,P=0.043)。PACG组右侧楔叶标准化节点度与VA呈负相关(r=-0.371,P=0.034)。PACG组其余脑区的标准化节点介数及标准化节点度值与RNFLT,静脉CDR、IOP及VA均未见明显相关。PACG患者静息态丘脑-皮层差异脑区均未发现与临床参数存在显著相关性。结论:(1)PACG组存在包括丘脑视觉传导通路及非视觉传导通路(感觉运动及情感记忆)的连接异常,且其可影响患者视觉相关的认知功能;(2)PACG组脑网络存在稳定且高效的“小世界”属性,且其整体构建具有均质化趋势;(3)PACG组视觉及非视觉(躯体运动)脑区的局部属性存在改变,且涉及到默认网络(default mode network,DMN),推测DMN可能是造成PACG患者内在心理活动异常的机制之一;(4)PACG组视觉脑区与VA相关,非视觉脑区分别与静脉CDR及VA相关。
[Abstract]:Objective: To study the functional connection of hypothalamic-cortical pathway in patients with primary closed-angle glaucoma (PACG) and the changes of brain network topology in patients with primary closed-angle glaucoma (PACG) by using functional connectivity (FC) and graph theory. With a view to raising awareness of possible neural mechanisms in PACG patients, help is provided for early diagnosis and treatment of PACG. Methods: 33 patients with PACG (PACG group) and 33 healthy controls (HC) matched with age and sex were recruited. All PACG patients underwent corresponding ophthalmic examinations, including retinal nerve fiber layer (RNFL) thickness, intraocular pressure (IOP), Venous cup ratio (CDR) and visual activity (VA). All subjects were scanned by SIEMENS Trio Tim 3.0T MR scanner to obtain a resting-state functional magnetic resonance image (RS-fMRI). Data processing is mainly divided into: (1) collecting rest state data; (2) carrying out data pretreatment using DPARIMA software package; (3) selecting 7 sub-regions of the double-side thalamus as a region of interest and ROI), and performing functional connection analysis on the seed points and the whole brain voxels; Two independent sample t test (AlphaSim correction, P0. 01) was carried out; (4) Gretna brain network analysis software package was applied, 116 automatic anatomical labeling (AAL) template brain regions were selected as nodes, the matrix was obtained after functional connection, and two-valued brain networks were constructed. The whole and local properties of the brain network were obtained, and the two-sample t-test (false display rate, FDR) and P0.05) were detected in the local attribute ascending group; (5) the correlation coefficient value and the network attribute value of the difference brain region were analyzed, and the correlation coefficient value and the network attribute value of the difference brain region were analyzed, and compared with the clinical parameter RNFLT and the vein CDR using SPSS v. 174.0 software. Pearson correlation analysis was performed between IOP and VA. Results: (1) Compared with HC group, the functional connection between thalamus and vision conduction pathway in PACG group (parietal lobe/ anterior lobe, frontal lobe/ frontal lobe) and non-visual conduction pathway (central paralobular, central posterior, marginal leaf/ hippocampus) was reduced, thalamus and visual conduction pathway (occipital lobe, (P <0.01, AlphaSim correction, cluster 72.29 voxel). (2) In the network sparsity (0. 1 ~ 0. 6), the standard convergence coefficient of the PACG and HC groups was standardized. 1. Standardization of the shortest path length (IRR) to be 1, and its small world index (INR)? 1. Both groups have "Little World" Properties. (3) Under the minimum and maximum network sparsity (0. 32 ~ 0. 42), the standard poly-coefficient (INR) of PACG group was slightly decreased compared with HC group (P: 0. 283 ~ 0. 453), and the standard shortest path length (LAI) was not changed (P: 0. 463 ~ 0. 93), which resulted in a slight decrease in the index of small world (P: 0. 322 ~ 0. 548). None of these differences were statistically significant (FDR correction, P0.05). In PACG group, the effects of total brain (E _ ()) and local (E _ (local)) did not change significantly (FDR correction, P0.05). (4) Under the minimum network sparsity (0. 32), compared with HC group, the normalized node degree of the early advanced visual cortex of PACG group (the peripheral cortex of the double-side margin, the back of the left occipital nerve, the back of the right occipital and the double-side wedge) was significantly decreased, and the posterior side vision pathway (right thalamus, The normalized node degrees were significantly increased (FDR correction, P0.05); back-side vision pathway (left occipital/ inferior), double-side wedge leaf, The number of normalized nodes in the left-hand tongue and the non-visual pathway (on the left-back lateral frontal, left-left orbital, left-hand, left-hand, left-hand, left-hand, cerebellar hemisphere, cerebellar vermis) was reduced, and the dorsal-ventral visual pathway (right-hand side), There was a significant increase in the number of normalized nodes (FDR correction, P0.05). (5) Under the minimum network sparsity (0. 32), the number of normalized nodes in the left orbital fraction of the PACG group was positively correlated with the venous CDR (r = 0.406, P = 0.019). The number of normalized nodes on the left margin of PACG group was positively correlated with VA (r = 0.357, P = 0.043); the number of normalized nodes on the right margin was positively correlated with VA (r = 0.0558, P = 0.0001); the number of normalized nodes on the left side was positively correlated with VA (r = 0.355, P = 0.043). There was a negative correlation between the normalized node degree and VA (r =-0.371, P = 0.037). The number of normalized nodes and normalized node degree values of the rest of the brain regions in the PACG group were not significantly correlated with RNFLT, venous CDR, IOP and VA. There was no significant correlation with clinical parameters in the resting thalamus-cortex difference brain regions of PACG patients. Conclusion: (1) The PACG group has an abnormal connection including the visual conduction pathway of thalamus and the non-visual conduction pathway (sensory and emotional memory), and it can influence the cognitive function of the patient's vision; (2) The PACG group has stable and high efficiency. "Little World" (3) The local attributes of PACG group visual and non-visual (somatic movement) brain regions are changed, and involve the default network (DMN). It is estimated that DMN may be one of the mechanisms that cause abnormal mental activity in PACG patients. (4) The visual brain regions of PACG group were associated with VA, and the non-visual brain regions were associated with venous CDR and VA, respectively.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R445.2;R775
本文编号：2298408
[Abstract]:Objective: To study the functional connection of hypothalamic-cortical pathway in patients with primary closed-angle glaucoma (PACG) and the changes of brain network topology in patients with primary closed-angle glaucoma (PACG) by using functional connectivity (FC) and graph theory. With a view to raising awareness of possible neural mechanisms in PACG patients, help is provided for early diagnosis and treatment of PACG. Methods: 33 patients with PACG (PACG group) and 33 healthy controls (HC) matched with age and sex were recruited. All PACG patients underwent corresponding ophthalmic examinations, including retinal nerve fiber layer (RNFL) thickness, intraocular pressure (IOP), Venous cup ratio (CDR) and visual activity (VA). All subjects were scanned by SIEMENS Trio Tim 3.0T MR scanner to obtain a resting-state functional magnetic resonance image (RS-fMRI). Data processing is mainly divided into: (1) collecting rest state data; (2) carrying out data pretreatment using DPARIMA software package; (3) selecting 7 sub-regions of the double-side thalamus as a region of interest and ROI), and performing functional connection analysis on the seed points and the whole brain voxels; Two independent sample t test (AlphaSim correction, P0. 01) was carried out; (4) Gretna brain network analysis software package was applied, 116 automatic anatomical labeling (AAL) template brain regions were selected as nodes, the matrix was obtained after functional connection, and two-valued brain networks were constructed. The whole and local properties of the brain network were obtained, and the two-sample t-test (false display rate, FDR) and P0.05) were detected in the local attribute ascending group; (5) the correlation coefficient value and the network attribute value of the difference brain region were analyzed, and the correlation coefficient value and the network attribute value of the difference brain region were analyzed, and compared with the clinical parameter RNFLT and the vein CDR using SPSS v. 174.0 software. Pearson correlation analysis was performed between IOP and VA. Results: (1) Compared with HC group, the functional connection between thalamus and vision conduction pathway in PACG group (parietal lobe/ anterior lobe, frontal lobe/ frontal lobe) and non-visual conduction pathway (central paralobular, central posterior, marginal leaf/ hippocampus) was reduced, thalamus and visual conduction pathway (occipital lobe, (P <0.01, AlphaSim correction, cluster 72.29 voxel). (2) In the network sparsity (0. 1 ~ 0. 6), the standard convergence coefficient of the PACG and HC groups was standardized. 1. Standardization of the shortest path length (IRR) to be 1, and its small world index (INR)? 1. Both groups have "Little World" Properties. (3) Under the minimum and maximum network sparsity (0. 32 ~ 0. 42), the standard poly-coefficient (INR) of PACG group was slightly decreased compared with HC group (P: 0. 283 ~ 0. 453), and the standard shortest path length (LAI) was not changed (P: 0. 463 ~ 0. 93), which resulted in a slight decrease in the index of small world (P: 0. 322 ~ 0. 548). None of these differences were statistically significant (FDR correction, P0.05). In PACG group, the effects of total brain (E _ ()) and local (E _ (local)) did not change significantly (FDR correction, P0.05). (4) Under the minimum network sparsity (0. 32), compared with HC group, the normalized node degree of the early advanced visual cortex of PACG group (the peripheral cortex of the double-side margin, the back of the left occipital nerve, the back of the right occipital and the double-side wedge) was significantly decreased, and the posterior side vision pathway (right thalamus, The normalized node degrees were significantly increased (FDR correction, P0.05); back-side vision pathway (left occipital/ inferior), double-side wedge leaf, The number of normalized nodes in the left-hand tongue and the non-visual pathway (on the left-back lateral frontal, left-left orbital, left-hand, left-hand, left-hand, left-hand, cerebellar hemisphere, cerebellar vermis) was reduced, and the dorsal-ventral visual pathway (right-hand side), There was a significant increase in the number of normalized nodes (FDR correction, P0.05). (5) Under the minimum network sparsity (0. 32), the number of normalized nodes in the left orbital fraction of the PACG group was positively correlated with the venous CDR (r = 0.406, P = 0.019). The number of normalized nodes on the left margin of PACG group was positively correlated with VA (r = 0.357, P = 0.043); the number of normalized nodes on the right margin was positively correlated with VA (r = 0.0558, P = 0.0001); the number of normalized nodes on the left side was positively correlated with VA (r = 0.355, P = 0.043). There was a negative correlation between the normalized node degree and VA (r =-0.371, P = 0.037). The number of normalized nodes and normalized node degree values of the rest of the brain regions in the PACG group were not significantly correlated with RNFLT, venous CDR, IOP and VA. There was no significant correlation with clinical parameters in the resting thalamus-cortex difference brain regions of PACG patients. Conclusion: (1) The PACG group has an abnormal connection including the visual conduction pathway of thalamus and the non-visual conduction pathway (sensory and emotional memory), and it can influence the cognitive function of the patient's vision; (2) The PACG group has stable and high efficiency. "Little World" (3) The local attributes of PACG group visual and non-visual (somatic movement) brain regions are changed, and involve the default network (DMN). It is estimated that DMN may be one of the mechanisms that cause abnormal mental activity in PACG patients. (4) The visual brain regions of PACG group were associated with VA, and the non-visual brain regions were associated with venous CDR and VA, respectively.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R445.2;R775
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