Diffusion fMRI detects white-matter dysfunction in mice with acute optic neuritis.

Diffusion fMRI detects white-matter dysfunction in mice with acute optic neuritis.
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DOI:
10.1016/j.nbd.2014.02.007
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发表时间:
2014-07
影响因子:
6.1
通讯作者:
Song SK
Song SK
中科院分区:
医学1区
文献类型:
--
作者:
Lin TH;Spees WM;Chiang CW;Trinkaus K;Cross AH;Song SK

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视神经炎是多发性硬化症(MS)的常见和早期症状。常规磁共振(MR)技术提供了评估多种MS相关病理的方法,包括轴突损伤、脱髓鞘和炎症。一种直接和非侵入性探测白质功能的方法可以进一步阐明潜在的病理和功能障碍的相互作用。在此之前,我们证明了一个显着的27%的激活相关的水的表观扩散系数的减少垂直于轴突纤维(ADC值)在正常C57 BL/6小鼠视神经与视觉刺激扩散功能磁共振成像。在这里,我们应用这种方法来探讨视力,视神经病理,和扩散功能磁共振成像在实验性自身免疫性脑脊髓炎(EAE)小鼠模型的视神经炎之间的关系。视觉刺激在假EAE视神经中产生显著的25%(与基线相比)ADC Δ C降低,而在患有急性视神经炎的EAE小鼠中仅观察到7%(与基线相比)ADC Δ C降低。减少的活化相关的ADC反应与MRI后免疫组织化学确定的病理学(包括炎症、脱髓鞘和轴突损伤)相关。根据我们的实验标准,当合并EAE受影响组和假手术组时,也发现激活相关ADC的反应和视力之间的负相关性。结果表明,减少扩散功能磁共振成像直接反映受损的轴突激活EAE小鼠视神经炎。弥散功能磁共振成像有希望直接测量在体内白质功能障碍或治疗反应的MS患者。
Optic neuritis is a frequent and early symptom of multiple sclerosis (MS). Conventional magnetic resonance (MR) techniques provide means to assess multiple MS-related pathologies, including axonal injury, demyelination, and inflammation. A method to directly and non-invasively probe white-matter function could further elucidate the interplay of underlying pathologies and functional impairments. Previously, we demonstrated a significant 27% activation-associated decrease in the apparent diffusion coefficient of water perpendicular to the axonal fibers (ADC⊥) in normal C57BL/6 mouse optic nerve with visual stimulation using diffusion fMRI. Here we apply this approach to explore the relationship between visual acuity, optic nerve pathology, and diffusion fMRI in the experimental autoimmune encephalomyelitis (EAE) mouse model of optic neuritis. Visual stimulation produced a significant 25% (vs. baseline) ADC⊥ decrease in sham EAE optic nerves, while only a 7% (vs. baseline) ADC⊥ decrease was seen in EAE mice with acute optic neuritis. The reduced activation-associated ADC⊥ response correlated with post-MRI immunohistochemistry determined pathologies (including inflammation, demyelination, and axonal injury). The negative correlation between activation-associated ADC⊥ response and visual acuity was also found when pooling EAE-affected and sham groups under our experimental criteria. Results suggest that reduction in diffusion fMRI directly reflects impaired axonal-activation in EAE mice with optic neuritis. Diffusion fMRI holds promise for directly gauging in vivo white-matter dysfunction or therapeutic responses in MS patients.
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