A combined post-mortem magnetic resonance imaging and quantitative histological study of multiple sclerosis pathology.
A combined post-mortem magnetic resonance imaging and quantitative histological study of multiple sclerosis pathology.
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DOI：
10.1093/brain/aws242
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发表时间：
2012-10
期刊：
影响因子：
--
通讯作者：
Johansen-Berg H
中科院分区：
文献类型：
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作者：
Kolasinski J;Stagg CJ;Chance SA;Deluca GC;Esiri MM;Chang EH;Palace JA;McNab JA;Jenkinson M;Miller KL;Johansen-Berg H
多发性硬化症是一种慢性炎症性神经系统疾病，其特征是整个中枢神经系统的局灶性和弥漫性神经变性和脱髓鞘。影响病理进展的因素了解甚少。一种假设是，解剖上的连通性影响了神经变性的扩散。这预示着神经退化的测量将在相互连接的结构之间产生最强烈的关联。然而，这种模式很难通过死后神经病理学或单独的体内扫描来量化。在这项研究中，我们采用全脑死后磁共振成像和定量组织学的互补方法来评估多发性硬化症的病理模式。基于不同的神经解剖学和多发性硬化症的文献记载，我们考虑了两种丘脑-皮层投射系统：外侧膝状核到初级视觉皮层和丘脑中背核到前额皮质。在解剖学上不同的丘脑-皮层投影系统中，磁共振成像得出的皮层厚度与连接束的髓鞘形成和连接的丘脑核细胞密度都有显著的相关性。在不同的丘脑-皮层系统中，这些神经变性标志物之间不存在这种相关性。磁共振成像病变分析清楚地描绘了边界分明的皮层下病变，冲击着感兴趣的白质束；然而，病灶束重叠程度的定量分析未能证明与每个丘脑-皮质投影系统中弥漫性病理标记物的严重程度有任何明显的关联。两个白质束的弥散加权磁共振成像指标与组织学衍生的束髓鞘形成测量显着相关。这些数据首次证明了功能性解剖连通性与多发性硬化症病理扩散的相关性。此外，死后弥散加权磁共振成像指标与固定组织的组织学指标之间的持续关系进一步验证了成像在未来神经病理学研究中的潜力。
Multiple sclerosis is a chronic inflammatory neurological condition characterized by focal and diffuse neurodegeneration and demyelination throughout the central nervous system. Factors influencing the progression of pathology are poorly understood. One hypothesis is that anatomical connectivity influences the spread of neurodegeneration. This predicts that measures of neurodegeneration will correlate most strongly between interconnected structures. However, such patterns have been difficult to quantify through post-mortem neuropathology or in vivo scanning alone. In this study, we used the complementary approaches of whole brain post-mortem magnetic resonance imaging and quantitative histology to assess patterns of multiple sclerosis pathology. Two thalamo-cortical projection systems were considered based on their distinct neuroanatomy and their documented involvement in multiple sclerosis: lateral geniculate nucleus to primary visual cortex and mediodorsal nucleus of the thalamus to prefrontal cortex. Within the anatomically distinct thalamo-cortical projection systems, magnetic resonance imaging derived cortical thickness was correlated significantly with both a measure of myelination in the connected tract and a measure of connected thalamic nucleus cell density. Such correlations did not exist between these markers of neurodegeneration across different thalamo-cortical systems. Magnetic resonance imaging lesion analysis depicted clearly demarcated subcortical lesions impinging on the white matter tracts of interest; however, quantitation of the extent of lesion-tract overlap failed to demonstrate any appreciable association with the severity of markers of diffuse pathology within each thalamo-cortical projection system. Diffusion-weighted magnetic resonance imaging metrics in both white matter tracts were correlated significantly with a histologically derived measure of tract myelination. These data demonstrate for the first time the relevance of functional anatomical connectivity to the spread of multiple sclerosis pathology in a ‘tract-specific’ pattern. Furthermore, the persisting relationship between metrics from post-mortem diffusion-weighted magnetic resonance imaging and histological measures from fixed tissue further validates the potential of imaging for future neuropathological studies.