High field (9.4 Tesla) magnetic resonance imaging of cortical grey matter lesions in multiple sclerosis
High field (9.4 Tesla) magnetic resonance imaging of cortical grey matter lesions in multiple sclerosis
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DOI：
10.1093/brain/awp335
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发表时间：
2010-03-01
期刊：
影响因子：
14.5
通讯作者：
Miller, David H.
中科院分区：
文献类型：
--
作者：
Schmierer, Klaus;Parkes, Harold G.;Miller, David H.
多发性硬化症是一种中枢神经系统的炎症性退行性疾病。多发性硬化症最明显的病理改变是多灶性白色物质脱髓鞘，但灰质脱髓鞘对其临床表现可能具有同等或更大的重要性。为了评估病变在灰质和白色物质中的发病作用，并探索脱髓鞘和非病变脑组织之间的关联，需要工具来准确地描述这些组织成分中的每一个。由于其在检测白色病变方面的敏感性，1.5 T的T-2加权磁共振成像在多发性硬化的诊断中非常重要。然而，1.5 T的磁共振成像在很大程度上无法检测到灰质病变。在这项研究中，我们使用T-2加权磁共振成像在9.4 T检测固定死后多发性硬化症运动皮层灰质病变。此外，我们制作了T-1，T-2和磁化转移率图，并使用t检验和多元回归将这些指标与定量组织学[神经元密度，髓鞘碱性蛋白（反映髓鞘含量）和磷酸化神经丝（反映轴突面积）的免疫染色强度]相关联。在21个组织样本中，28个皮质灰质病变在T-2加权磁共振成像和髓鞘碱性蛋白免疫染色切片上均可见，15/28个为混合白色和灰质，11/28个为软膜下皮质灰质病变; 2/28个皮质灰质病变累及皮质的所有层。与非病变皮质相比，皮质灰质病变显示神经元密度降低（98/mm（2），SD = 34/mm（2;）vs 129/mm（2），SD = 44; P < 0.01），磷酸化神经丝（1/透射率= 1.16; SD = 0.09对比1.24; SD = 0.1; P < 0.01）和磁化传递率（31.1 pu; SD = 11.9 vs. 37.5 pu; SD = 8.7; P = 0.01），以及T-2增加（25.9; SD = 5 vs. 22.6 ms; SD = 4.7; P < 0.01）。磷酸化神经丝与髓鞘碱性蛋白（r = 0.58，P < 0.01）、髓鞘碱性蛋白与T-2（r =-0.59，P < 0.01）、神经元密度与T-1（r =-0.57，P < 0.01）相关。所有指标均与组织固定持续时间相关，然而，分析中包括后者并没有从根本上影响所描述的相关性。我们的数据表明，在9.4 T的T-2加权磁共振成像能够检测到死后多发性硬化症大脑皮质灰质病变。定量关联表明，在皮质灰质中，T-1可能是神经元密度的预测因子，而T-2可能是髓鞘含量（其次是轴突）的预测因子。将这些结果成功转化为使用高场磁共振成像（例如3 T和7 T）的体内研究将改善皮质病理学的评估，从而对多发性硬化症患者的诊断和自然史研究以及预防皮质脱髓鞘和神经元丢失的假定治疗的临床试验设计产生影响。
Multiple sclerosis is an inflammatory, degenerative disease of the central nervous system. The most obvious pathological change in multiple sclerosis is multifocal demyelination of the white matter, but grey matter demyelination may be of equal or even greater importance for its clinical manifestations. In order to assess the pathogenetic role of lesions in the grey and white matter, and to explore the association between demyelinated and non-lesional brain tissue, tools are needed to depict each of these tissue components accurately in vivo. Due to its sensitivity in detecting white matter lesions, T-2-weighted magnetic resonance imaging at 1.5 T is important in the diagnosis of multiple sclerosis. However, magnetic resonance imaging at 1.5 T largely fails to detect grey matter lesions. In this study, we used T-2-weighted magnetic resonance imaging at 9.4 T to detect grey matter lesions in fixed post-mortem multiple sclerosis motor cortex. Furthermore, we produced T-1, T-2 and magnetization transfer ratio maps, and correlated these indices with quantitative histology [neuronal density, intensity of immunostaining for myelin basic protein (reflecting myelin content) and phosphorylated neurofilament (reflecting axonal area)] using t-tests and multivariate regression. In 21 tissue samples, 28 cortical grey matter lesions were visible on both T-2-weighted magnetic resonance imaging and sections immunostained for myelin basic protein, 15/28 being mixed white and grey matter and 11/28 subpial cortical grey matter lesions; 2/28 cortical grey matter lesions involved all layers of the cortex. Compared with non-lesional cortex, cortical grey matter lesions showed reduction of neuronal density (98/mm(2), SD = 34/mm(2;) versus 129/mm(2), SD = 44; P < 0.01), phosphorylated neurofilament (1/transmittance = 1.16; SD = 0.09 versus 1.24; SD = 0.1; P < 0.01) and magnetization transfer ratio (31.1 pu; SD = 11.9 versus 37.5 pu; SD = 8.7; P = 0.01), and an increase of T-2 (25.9; SD = 5 versus 22.6 ms; SD = 4.7; P < 0.01). Associations were detected between phosphorylated neurofilament and myelin basic protein (r = 0.58, P < 0.01), myelin basic protein and T-2 (r = -0.59, P < 0.01), and neuronal density and T-1 (r = -0.57, P < 0.01). All indices correlated with duration of tissue fixation, however, including the latter in the analysis did not fundamentally affect the associations described. Our data show that T-2-weighted magnetic resonance imaging at 9.4 T enables detection of cortical grey matter lesion in post-mortem multiple sclerosis brain. The quantitative associations suggest that in cortical grey matter T-1 may be a predictor of neuronal density, and T-2 of myelin content (and-secondarily-axons). Successful translation of these results into in vivo studies using high field magnetic resonance imaging (e.g. 3 T and 7 T) will improve the assessment of cortical pathology and thereby have an impact on the diagnosis and natural history studies of patients with multiple sclerosis, as well as clinical trial designs for putative treatments to prevent cortical demyelination and neuronal loss.