Wu Qizhu, Butzkueven Helmut, Gresle Melissa, Kirchhoff Frank, Friedhuber Anna, Yang Qing, Wang Hong, Fang Ke, Lei Hao, Egan Gary F, Kilpatrick Trevor J
Howard Florey Institute, University of Melbourne, VIC 3010, Australia.
Neuroimage. 2007 Oct 1;37(4):1138-47. doi: 10.1016/j.neuroimage.2007.06.029. Epub 2007 Jul 13.
Diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) are widely used to investigate central nervous system (CNS) white matter structure and pathology. Changes in principal diffusivities parallel and perpendicular to nerve fibers or axonal tracts have been associated with axonal pathology and de/dysmyelination respectively. However, the ultra-structural properties and the pathological alterations of white matter responsible for diffusivity changes have not been fully elucidated. We examined the relationship between the directional diffusivities and ultra-structural properties in mouse optic nerve using healthy animals, and mice with optic neuritis (ON) that exhibited marked inflammatory changes and moderately severe axonal pathology. Progressive axonal degeneration in ON resulted in a 23% reduction of parallel diffusivity as detected by diffusion MRI (P<10(-5)), but no change in perpendicular diffusivity. Parallel diffusion changes were highly correlated with the total axolemmal cross-sectional area in the pre-chiasmal portion of the optic nerve (r=0.86, P<0.001). This study provides quantitative evidence that reduced parallel diffusivity in the optic nerve correlates significantly with axolemmal cross-sectional area reductions. MRI-based assessment of axonal degeneration in murine ON is feasible and potentially useful for monitoring of neuro-protective therapies in preclinical trials in animals.
扩散加权成像（DWI）和扩散张量成像（DTI）被广泛用于研究中枢神经系统（CNS）白质结构和病理学。与神经纤维或轴突束平行和垂直的主要扩散率变化分别与轴突病理学和脱髓鞘/髓鞘形成异常有关。然而，导致扩散率变化的白质超微结构特性和病理改变尚未完全阐明。我们使用健康动物以及患有视神经炎（ON）且表现出明显炎症变化和中度严重轴突病理学改变的小鼠，研究了小鼠视神经中方向扩散率与超微结构特性之间的关系。视神经炎中进行性轴突退变导致扩散磁共振成像检测到平行扩散率降低23%（P<10(-5)），但垂直扩散率无变化。平行扩散变化与视神经视交叉前部分的总轴膜横截面积高度相关（r = 0.86，P<0.001）。本研究提供了定量证据，表明视神经中平行扩散率降低与轴膜横截面积减少显著相关。基于磁共振成像评估小鼠视神经炎中的轴突退变是可行的，并且可能有助于在动物临床试验中监测神经保护疗法。
