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Directional diffusivity as a magnetic resonance (MR) biomarker in demyelinating disease

机译:定向扩散作为脱髓鞘疾病的磁共振(MR)生物标志物

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Directional diffusivities derived from diffusion tensor magnetic resonance imaging (DTI) measurements describe water movement parallel to (λ_‖, axial diffusivity) and perpendicular to λ_⊥, radial diffusivity) axonal tracts. λ_‖ and λ_⊥ have been shown to differentially detect axon and myelin abnormalities in several mouse models of central nervous system white matter pathology in our laboratory. These models include experimental autoimmune encephalomyelitis (EAE), (1) myelin basic protein mutant mice with dysmyelination and intact axons, (2) cuprizone-induced demyelination, and remyelination, with reversible axon injury (2, 3) and a model of retinal ischemia in which retinal ganglion cell death is followed by Wallerian degeneration of optic nerve, with axonal injury preceding demyelination. (4) Decreased λ_‖ correlates with acute axonal injury and increased λ_⊥ indicates myelin damage. (4) More recently, we have translated this approach to human MR, investigating acute and chronic optic neuritis in adults with multiple sclerosis, brain lesions in adults with multiple sclerosis, and acute disseminated encephalomyelitis (ADEM) in children. We are also investigating the use of this technique to probe the underlying structural change of the cervical spinal cord in acute and chronic T2-hyperintense lesions in spinal stenosis, trauma, and transverse myelitis. In each of these demyelinating diseases, the discrimination between axonal and myelin injury which we can achieve has important prognostic and therapeutic implications. For those patients with myelin injury but intact axons, early, directed drug therapy has the potential to prevent progression to axonal loss and permanent disability.
机译:从扩散张量磁共振成像(DTI)测量得出的方向扩散率描述了平行于(λ_‖,轴向扩散率)和垂直于λ_⊥(径向扩散率)轴突的水运动。在我们实验室的几种中枢神经系统白质病理小鼠模型中,λ_和λ_⊥已被证明可以差异检测轴突和髓鞘异常。这些模型包括实验性自身免疫性脑脊髓炎(EAE),(1)具有髓鞘异常和轴突完整的髓鞘碱性蛋白突变小鼠,(2)铜氮酮诱导的脱髓鞘和再髓鞘性,可逆性轴突损伤(2、3)和视网膜缺血模型其中视网膜神经节细胞死亡,然后是视神经的沃勒氏变性,在脱髓鞘之前有轴突损伤。 (4)λ__的减少与急性轴突损伤相关,而λ_⊥的增加则表明髓磷脂受损。 (4)最近,我们将这种方法应用于人类MR,研究了多发性硬化症成年人的急,慢性视神经炎,多发性硬化症成年人的脑损伤以及儿童的急性弥漫性脑脊髓炎(ADEM)。我们也正在研究使用该技术来探究在椎管狭窄,创伤和横断性脊髓炎的急性和慢性T2高强度病变中子宫颈脊髓的潜在结构变化。在每种脱髓鞘疾病中,我们可以实现的对轴突和髓鞘损伤的区分具有重要的预后和治疗意义。对于那些髓鞘损伤但轴突完整的患者,早期的定向药物治疗有可能防止发展为轴突丢失和永久性残疾。

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