用11.7 T扩散加权磁共振波谱探测cuprizone小鼠模型中炎症驱动的胶质细胞改变
Inflammation-driven glial alterations in the cuprizone mouse model probed with diffusion-weighted magnetic resonance spectroscopy at 11.7 T
摘要：
脑组织的炎症是免疫系统对有毒化合物的存在或对细胞损伤的复杂反应，导致包括神经胶质细胞活化的级联病理过程。神经胶质反应性的非侵入性磁共振成像标记物对于脑中炎症过程的体内检测和监测以及用于评估个性化治疗的功效将是非常有用的。由于它们在神经胶质细胞中的特定位置，肌醇（mIns）和胆碱化合物（tCho）似乎是探测神经胶质细胞特异性细胞内区室的最佳候选物。然而，使用常规质子磁共振波谱（MRS）定量的它们的浓度对炎症没有特异性。相反，最近有人提出，在反应性星形胶质细胞的小鼠模型中使用扩散加权MRS（DW-MRS）测量的mIns细胞内扩散可能是星形胶质细胞肥大的特异性标志物。为了评估mIns和tCho扩散对炎症驱动的神经胶质细胞改变的特异性，我们在中毒6周后在cuprizone喂养的小鼠胼胝体中进行DW-MRS，并使用免疫组织化学评估星形胶质细胞和小胶质细胞改变的程度。与对照小鼠相比，mIns和tCho表观扩散系数在cuprizone喂养的小鼠中显著升高，而组织学评价证实存在严重炎症。此外，mIns和tCho扩散分别显示出与星形胶质细胞和小胶质细胞面积分数的组织学测量的强相关性和中等相关性，证实DW-MRS是病理条件下特异性检测胶质细胞变化的有前途的工具。
英文摘要：
Inflammation of brain tissue is a complex response of the immune system to the presence of toxic compounds or to cell injury, leading to a cascade of pathological processes that include glial cell activation. Noninvasive magnetic resonance imaging markers of glial reactivity would be very useful for in vivo detection and monitoring of inflammation processes in the brain, as well as for evaluating the efficacy of personalized treatments. Due to their specific location in glial cells, myo-inositol (mIns) and choline compounds (tCho) seem the best candidates for probing glial-specific intra-cellular compartments. However, their concentrations quantified using conventional proton magnetic resonance spectroscopy (MRS) are not specific for inflammation. In contrast, it has been recently suggested that mIns intra-cellular diffusion, measured using diffusion-weighted MRS (DW-MRS) in a mouse model of reactive astrocytes, could be a specific marker of astrocytic hypertrophy. In order to evaluate the specificity of both mIns and tCho diffusion to inflammation-driven glial alterations, we performed DW-MRS in the corpus callosum of cuprizone-fed mice after 6 weeks of intoxication and evaluated the extent of astrocytic and microglial alterations using immunohistochemistry. Both mIns and tCho apparent diffusion coefficients were significantly elevated in cuprizone-fed mice compared to control mice, while histologic evaluation confirmed the presence of severe inflammation. Additionally, mIns and tCho diffusion showed, respectively, strong and moderate correlations with histological measures of astrocytic and microglial area fractions, confirming DW-MRS as a promising tool for specific detection of glial changes under pathological conditions.
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