本文選題：外側(cè)膝狀體 + 原發(fā)性開角型青光眼��； 參考：《華中科技大學(xué)》2012年博士論文

【摘要】：青光眼是世界上第一位不可逆性致盲眼病,是一組以進(jìn)行性視網(wǎng)膜神經(jīng)節(jié)細(xì)胞及其軸突的丟失為特征的視神經(jīng)病變。已有研究證實(shí)原發(fā)性開角型青光眼神經(jīng)損傷不僅僅局限于眼部,而且累及全視路。目前該疾病中樞損害的研究數(shù)據(jù)多來自動(dòng)物實(shí)驗(yàn)。磁共振成像技術(shù)具有無創(chuàng)、可重復(fù)、高的時(shí)間和空間分辨率等特點(diǎn),已被廣泛應(yīng)用于腦神經(jīng)科學(xué)的基礎(chǔ)研究和臨床應(yīng)用中,為在體研究原發(fā)性開角型青光眼腦損害機(jī)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術(shù),從形態(tài)學(xué)及功能學(xué)相結(jié)合的角度,探討原發(fā)性開角型青光眼患者外側(cè)膝狀體形態(tài)變化、中樞視路神經(jīng)纖維改變及靜息態(tài)腦功能變化的特點(diǎn)。 第一部分 原發(fā)性開角型青光眼的外側(cè)膝狀體形態(tài)學(xué)改變 目的：觀察原發(fā)性開角型青光眼(Primary open-angle glaucoma, POAG)患者外側(cè)膝狀體(Lateral geniculate nucleus, LGN)最大高徑及體積的變化,并分析與視神經(jīng)及視功能損害的相關(guān)性特點(diǎn)。 方法：選取25名POAG患者(男19例,女6例,21-54歲)及與之年齡性別匹配的正常人24例(男19例,女5例,21-55歲),經(jīng)青光眼專科檢查采集眼部臨床數(shù)據(jù)：如視盤分析(Cup-to-disc ratio, CDR)、視網(wǎng)膜神經(jīng)纖維層厚度分析(Retinal nerve fiber layer thickness, RNFLT)、視野檢查(Mean sensitivity,MS和Mean defect, MD*)等,使用3.0T GE磁共振掃描儀,所有受試者采用3D-BRAVO及Proton density序列完成LGN掃描,使用Advantage work-station軟件測(cè)量雙側(cè)LGN的最大高徑及體積,對(duì)比兩組之間的LGN形態(tài)學(xué)差異,并分析與視神經(jīng)CDR、RNFLT及視野檢查MS、MD*的相關(guān)性。 結(jié)果：POAG組雙側(cè)LGN最大高徑(右側(cè)4.36±0.62mm,左側(cè)4.32±0.62mm)及體積(右側(cè)97.48±27.61mm3,左側(cè)92.68±25.79mm3)小于正常對(duì)照組(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最大高徑及體積與眼部視神經(jīng)的CDR呈負(fù)相關(guān),與RNFLT呈正相關(guān),與視野檢查的MS值呈正相關(guān),與MD*值呈負(fù)相關(guān)(p0.05)。正常人LGN最大高徑及體積與年齡無顯著相關(guān)性,與眼部視神經(jīng)的CDR及RNFLT無顯著相關(guān)性(p0.05)。 結(jié)論：POAG神經(jīng)損傷跨突觸累及雙側(cè)LGN,且其萎縮與眼部視神經(jīng)損傷及視功能缺損顯著相關(guān)。本研究中所開展的LGN最大高徑及體積測(cè)量,可用以研究POAG中樞損傷,并為視神經(jīng)及視功能損害程度的臨床診斷評(píng)估提供客觀指標(biāo)。 第二部分POAG患者的中樞視路神經(jīng)纖維改變 目的：觀察POAG患者中樞視路神經(jīng)纖維改變的部位及性質(zhì),并分析與視神經(jīng)、視功能損害及LGN形態(tài)變化的相關(guān)性。 方法：入組的25例POAG患者及24例正常人,所有受試者接受3.0T GE磁共振掃描儀完成全腦彌散張量成像(Diffusion tensor imaging, DTI)掃描,使用FMRIB's Diffusion Toolbox軟件,采用基于神經(jīng)束空間統(tǒng)計(jì)學(xué)(Tract-based spatial statistics, TBSS)的DTI數(shù)據(jù)分析方法,分析出兩組之間中樞視路神經(jīng)纖維彌散特性有差異的部位,計(jì)算出差異部位的彌散參數(shù)各向異性分?jǐn)?shù)(Fractional anisotropy, FA)及平均彌散值(Mean diffusivity, MD),并分析與視神經(jīng)CDR、RNFLT及視野檢查MS、MD*值及LGN形態(tài)學(xué)的相關(guān)性。 結(jié)果：POAG組雙側(cè)視束及視放射神經(jīng)纖維彌散特性與正常組存在顯著差異,表現(xiàn)為FA值降低,MD值升高(p0.05)。POAG組中,患者視束及視放射FA值與CDR、RNFLT、視野檢查的MS及MD*有顯著相關(guān)性(p0.05)；視束MD值與視神經(jīng)及視功能損害有相關(guān)性(p0.05),且與視神經(jīng)損傷相關(guān)性更好；而視放射MD值與視神經(jīng)及視功能損害均無相關(guān)性(p0.05)。POAG患者視束及視放射FA值與LGN最大高徑及體積呈顯著正相關(guān)(p0.05),MD值與其無相關(guān)性(p0.05)。與所匹配正常人對(duì)比,POAG患者視束FA及MD值的改變要大于視放射(p0.05)。正常組雙側(cè)視束及視放射神經(jīng)纖維彌散特性(FA值及MD值)與年齡無顯著相關(guān)性(p0.05)。 結(jié)論：POAG患者視束及視放射神經(jīng)纖維的損傷,與眼部視神經(jīng)、視功能損傷及LGN形態(tài)改變顯著相關(guān),FA值與其相關(guān)性更好；且視束損傷較視放射腰嚴(yán)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中樞視路神經(jīng)纖維損傷。 第三部分POAG患者的靜息態(tài)腦功能變化 目的：探討POAG患者靜息態(tài)腦功能活動(dòng)與正常人之間的差異。 方法：入組的25例POAG患者及24例正常人,均經(jīng)3.0T GE磁共振掃描儀,完成全腦靜息態(tài)功能磁共振掃描,使用REST軟件及局部一致性(Regional homogeneity, ReHo)的分析方法,分析出兩組之間靜息態(tài)腦功能活動(dòng)有統(tǒng)計(jì)學(xué)差異的腦區(qū)。 結(jié)果：與正常對(duì)照組相比,POAG患者的雙側(cè)枕葉、額下回、右側(cè)顳葉靜息態(tài)腦活動(dòng)的ReHo值降低(p0.05)；雙側(cè)背側(cè)丘腦、額上回、腦橋背部、梭狀回靜息態(tài)腦活動(dòng)ReHo值增高(p0.05)。 結(jié)論：POAG患者多個(gè)腦區(qū)靜息態(tài)腦功能活動(dòng)表現(xiàn)異常,這種多腦區(qū)的功能紊亂可能參與POAG的發(fā)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.

【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類號(hào)】：R775

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本文編號(hào)：1788073