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首页> 外文OA文献 >Alternative Neuropsychological and Magnetic Resonance Imaging Measures in Multiple Sclerosis: Exploring the relation between brain lesion measured by diffusion tensor magnetic resonance imaging and interhemispheric communication and processing speed in multiple sclerosis
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Alternative Neuropsychological and Magnetic Resonance Imaging Measures in Multiple Sclerosis: Exploring the relation between brain lesion measured by diffusion tensor magnetic resonance imaging and interhemispheric communication and processing speed in multiple sclerosis

机译：多发性硬化症的替代神经心理学和磁共振成像测量：探讨弥散张量磁共振成像测量的脑损伤与半球间通信和多发性硬化的处理速度之间的关系

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摘要

Multiple sclerosis (MS) is a chronic neurological disease of the central nerve system that affects young adults with a higher prevalence in women (ratio 3:2). The neuropathology of the disease is characterised by demyelination of the white matter in the brain and central cord. MS may involve degeneration of white matter throughout the nervous system, with a predilection for specific target zones that includes the corpus callosum. The pathologic process may lead to motor problems, but halve of the patients has cognitive problems associated with MS. In this thesis, we focus on the cognitive problems and the relation with neuropathological brain damage. One of the brain areas preferentially involved in MS, is the corpus callosum. This brain structure is the largest white matter tract connecting both hemispheres. Research in callosotomy patients, acallosal patients and callosal section patients indicates that robust callosal damage may lead to interhemispheric transfer dysfunctions. In the first part of this thesis callosal problems in MS are explored. Damage to the corpus callosum in this patient group is subtler than in callosotomy patients. Moreover, the callosal damage strongly varies from patient to patient. In this thesis the redundancy gain paradigm, a behavioural measure to investigate interhemispheric communication is used. In this task, flashes of light are presented to the left, right or bilateral (left and right simultaneously) visual hemifield while the subject fixates to the middle of the screen. As soon as the subject detects a flash, he presses the response button with the left or right hand (detection task). An effect that is typically observed in healthy subjects is that reaction times to bilateral stimuli are faster than to unilateral stimuli. This effect is referred to as the redundancy gain effect. Previous research shows that the redundancy gain effect is enlarged in patients with callosal problems (acallosal patients or patients with callosal section). The results in this thesis show, in analogy with the results in patients with robust callosal damage, an enlarged redundancy gain effect for MS patients. These results demonstrate the sensitiveness of the redundancy gain paradigm to investigate callosal problems in MS. To explore the effect of the amount of callosal brain damage on the redundancy gain effect, the callosal damage needs to be quantified. For this purpose diffusion tensor imaging was used. With this technique, water diffusion in the white matter can be investigated. Water in the brain spreads preferentially along the direction of the axonal fibers. Intact myelin sheets are effective barriers for the water. Demyelination, an important pathological aspect of MS, leads to decreased delineation of the tracts along which the water spreads. This results in changed diffusion derived measures. Fractional anisotropy is an important diffusion derived measure for inter- and intravoxel fiber coherence. Previous research shows that fractional anisotropy is decreased in MS patients compared to healthy controls. To calculate the fractional anisotropy, diffusion measures along three directions are defined, more specific along the principal direction, along the direction of minimal diffusion and along a third Alternative Neuropsychological and MRI Measures in MS 89 Summary direction that is orthogonal to the previous two. With this information, the longitudinal and transverse diffusivity can be calculated. Longitudinal diffusivity is the diffusion eigenvalue along the principal direction, whereas the transverse diffusivity is the mean of the eigenvalues along the other two directions. Recent research shows that demyelination and axonal loss, specific for MS pathology, is characterised by increased transverse diffusivity. Hence, transverse diffusivity is a unique marker for MS. The results of this thesis confirm this and show that transverse diffusivity is significantly more increased than longitudinal diffusivity in MS patients compared to healthy matched controls. Thirdly, a correlation between the behavioural results, the redundancy gain effect, and the brain imaging measures, the diffusion derived measures, was found: the larger the transverse diffusivity, or in other words, the MS related callosal damage, the larger the redundancy gain effect in MS patients. Moreover, neither longitudinal diffusivity, nor callosal lesion load as defined on conventional T2 images were additional factors in explaining this correlation. The results of the first part of this thesis show a) that the redundancy gain paradigm is a sensitive measure to investigate callosal brain damage in MS, b) that diffusion derived parameters are subtle measures to indicate MS related brain damage and c) that a significant correlation between callosal brain damage and the redundancy gain effect could be found in MS patients. In the second part of this thesis the focus was on the relation between cerebral brain damage as defined by diffusion derived measures and information processing speed in MS. Information processing speed is a cognitive measure tested by the Paced Serial Addition Test (PASAT) and the Symbol Digit Modalities Test (SDMT), two commonly used neuropsychological tests in MS. A significant correlation between the performance on the SDMT and transverse diffusivity in the whole brain was found in MS patients, indicating that demyelination and axonal damage, characteristic for MS pathology, are important factors for explaining the slowed information processing speed in MS. No correlation was found with the performance on the PASAT, which can be explained by the weaker psychometric qualities of the PASAT compared to the SDMT. First of all, the results of this thesis corroborate the heterogeneous pathological condition in MS. Research on callosal problems in MS can not be done without considering these individual differences. Based on our results, diffusion weighted imaging seems to offer a promising technique to determine cerebral damage in MS. Transverse diffusivity, considered to be a unique benchmark of white matter demyelination as seen in MS, is of special interest. Moreover, this diffusion derived measures correlate with cognitive (dys)function in MS, a correlation not consistently found for conventional imaging (lesion load on T2 of T1 images).
机译：多发性硬化症（MS）是中枢神经系统的一种慢性神经系统疾病，会影响青壮年，女性患病率更高（比率3：2）。该疾病的神经病理学特征是大脑和中枢脊髓中的白质脱髓鞘。 MS可能涉及整个神经系统中的白质变性，尤其是包括specific体的特定目标区域。病理过程可能导致运动问题，但一半的患者存在与MS相关的认知问题。在本文中，我们着重于认知问题以及与神经病理性脑损伤的关系。优先参与MS的大脑区域之一是call体。这种大脑结构是连接两个半球的最大白质束。对call骨切开术患者，call骨病患者和call骨切片患者的研究表明，健壮的call骨损伤可能导致半球间转移功能障碍。在本文的第一部分中，探讨了MS中的常见问题。与call切开术患者相比，该患者组对call体的损伤微妙。此外，call骨损伤因患者而异。本文采用冗余增益范式，一种研究半球间通信的行为方法。在此任务中，闪光灯会显示在左，右或双侧（同时左和右）视觉半场，而对象固定在屏幕中间。一旦对象检测到闪烁，他就用左手或右手按下响应按钮（检测任务）。在健康受试者中通常观察到的一种效果是，对双侧刺激的反应时间快于对单侧刺激的反应时间。该效应称为冗余增益效应。先前的研究表明，在有call骨问题的患者（有call骨的患者或有os骨切片的患者）中，冗余度增加效应得到了扩大。本论文的结果表明，与健壮性call骨损伤患者的结果相似，MS患者具有更大的冗余增加效果。这些结果表明冗余增益范式的敏感性研究MS中的call问题。为了探究愈伤性脑损伤的数量对冗余获得效应的影响，愈伤性损伤需要被量化。为此目的，使用了扩散张量成像。利用这种技术，可以研究白质中的水扩散。大脑中的水优先沿着轴突纤维的方向扩散。完整的髓磷脂片是有效的防水屏障。脱髓鞘是MS的重要病理学方面，导致水沿其扩散的区域的轮廓减少。这导致改变了由扩散得出的量度。分数各向异性是体素内部和体素内部纤维相干性的重要扩散指标。先前的研究表明，与健康对照组相比，MS患者的分数各向异性有所降低。为了计算分数各向异性，定义了沿三个方向的扩散度量，更具体地沿主方向，最小扩散方向以及沿MS 89摘要方向与前两个正交的第三种替代神经心理学和MRI度量。利用该信息，可以计算出纵向和横向扩散率。纵向扩散率是沿主方向的扩散特征值，而横向扩散率是沿其他两个方向的特征值的平均值。最近的研究表明，MS病理学特有的脱髓鞘和轴突丢失的特点是横向扩散性增加。因此，横向扩散率是MS的独特标记。本文的结果证实了这一点，并表明与健康匹配的对照组相比，MS患者的横向扩散率明显高于纵向扩散率。第三，发现行为结果，冗余度增益效果和脑成像指标（即扩散衍生指标）之间的相关性：横向扩散系数越大，换句话说，与MS相关的call损伤，冗余度增益越大。对MS患者有效。此外，在传统T2图像上定义的纵向扩散率或call部病变负荷都不是解释这种相关性的其他因素。本论文第一部分的结果表明：a）冗余增益范例是研究MS call脑损伤的一种敏感措施。b）扩散得出的参数是指示MS相关脑损伤的微妙措施，c）在MS患者中发现call骨脑损伤与冗余度增加效果之间存在显着相关性。在本文的第二部分中，重点讨论了由扩散得出的措施定义的脑部脑损伤与MS中信息处理速度之间的关系。信息处理速度是一种认知度量，它是通过连续序列附加测验（PASAT）和符号数字模态测验（SDMT）来测试的，这是MS中两种常用的神经心理学测验。 MS患者在SDMT的表现与全脑横向扩散之间存在显着相关性，这表明MS病理特征的脱髓鞘和轴突损伤是解释MS信息处理速度降低的重要因素。没有发现与PASAT的表现相关，这可以用PASAT的心理测量质量较SDMT弱来解释。首先，本论文的结果证实了MS的异质性病理状况。如果不考虑这些个体差异，就无法对MS中的call音问题进行研究。根据我们的结果，弥散加权成像似乎为确定MS的脑损伤提供了一种有前途的技术。横向扩散率，被认为是MS中白质脱髓鞘的唯一基准，引起了人们的特别关注。此外，这种由扩散得出的量度与MS中的认知（功能障碍）功能相关，而对于常规成像（T1图像的T2上的病变负荷）并不能始终如一地发现这种相关性。

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    Warlop Nele;

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  • 年度 2009
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  • 正文语种 eng
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