Biophysical modeling of high field diffusion MRI demonstrates micro-structural aberration in chronic mild stress rat brain.
Biophysical modeling of high field diffusion MRI demonstrates micro-structural aberration in chronic mild stress rat brain.
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DOI：
10.1016/j.neuroimage.2016.07.001
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发表时间：
2016-11-15
期刊：
影响因子：
5.7
通讯作者：
Jespersen SN
中科院分区：
文献类型：
--
作者：
Khan AR;Chuhutin A;Wiborg O;Kroenke CD;Nyengaard JR;Hansen B;Jespersen SN
抑郁症是全世界残疾的主要原因之一。抑郁症症状的巨大异质性导致诊断困难，迄今为止，还没有确定的生物标志物或成像方法来检查抑郁症。在动物受试者研究中，不可预测的慢性轻度应激（CMS）引起的快感缺乏被认为是抑郁症的现实模型。体视学和神经元追踪技术已经证明 CMS 大脑的海马体、前额皮质和杏仁核的微观结构持续重塑。扩散 MRI (d-MRI) 分析的最新发展，例如神经突密度和扩散峰度成像 (DKI)，能够捕获微观结构变化，并被认为是临床前和临床成像的强大工具。本研究利用 d-MRI 分析神经突密度模型和 DKI 框架，通过与正常对照组的大脑进行比较，研究 CMS 大鼠大脑海马、前额皮质、尾壳核和杏仁核区域的微观结构。为了验证 CMS 诱导的微观结构改变的结果，进行组织学测定神经突、核和星形胶质细胞密度。 CMS 大鼠大脑杏仁核中基于 d-MRI 的神经突密度和基于张量的平均峰度 (MKT) 显着较高，而平均扩散率 (MD)、细胞外扩散率 (Deff) 和神经突内扩散率 (DL) 显着较低。在压力组中，海马体和尾壳核的 Deff 也显着降低。组织学神经突密度证实了杏仁核的 d-MRI 结果，核和星形胶质细胞密度的降低进一步支持了 d-MRI 结果。本研究表明，基于 d-MRI 的神经突密度和 MKT 可以揭示 CMS 大鼠大脑的特定微观结构变化，这些参数可能对抑郁症的临床诊断和治疗效果评估具有价值。
Depression is one of the leading causes of disability worldwide. Immense heterogeneity in symptoms of depression causes difficulty in diagnosis, and to date, there are no established biomarkers or imaging methods to examine depression. Unpredictable chronic mild stress (CMS) induced anhedonia is considered to be a realistic model of depression in studies of animal subjects. Stereological and neuronal tracing techniques have demonstrated persistent remodeling of microstructure in hippocampus, prefrontal cortex and amygdala of CMS brains. Recent developments in diffusion MRI (d-MRI) analyses, such as neurite density and diffusion kurtosis imaging (DKI), are able to capture microstructural changes and are considered to be robust tools in preclinical and clinical imaging. The present study utilized d-MRI analyzed with a neurite density model and the DKI framework to investigate microstructure in the hippocampus, prefrontal cortex, caudate putamen and amygdala regions of CMS rat brains by comparison to brains from normal controls. To validate findings of CMS induced microstructural alteration, histology was performed to determine neurite, nuclear and astrocyte density. d-MRI based neurite density and tensor-based mean kurtosis (MKT) were significantly higher, while mean diffusivity (MD), extracellular diffusivity (Deff) and intra-neurite diffusivity(DL) were significantly lower in the amygdala of CMS rat brains. Deff was also significantly lower in the hippocampus and caudate putamen in stressed groups. Histological neurite density corroborated the d-MRI findings in the amygdala and reductions in nuclear and astrocyte density further buttressed the d-MRI results. The present study demonstrated that the d-MRI based neurite density and MKT can reveal specific microstructural changes in CMS rat brains and these parameters might have value in clinical diagnosis of depression and for evaluation of treatment efficacy.
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