Axonal disruption in white matter underlying cortical sulcus tau pathology in chronic traumatic encephalopathy
Axonal disruption in white matter underlying cortical sulcus tau pathology in chronic traumatic encephalopathy
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DOI：
10.1007/s00401-017-1686-x
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发表时间：
2017-03-01
影响因子：
12.7
通讯作者：
Brody, David L.
中科院分区：
文献类型：
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作者：
Holleran, Laurena;Kim, Joong Hee;Brody, David L.
慢性创伤性脑病（CTE）是一种与重复性创伤性脑损伤相关的进行性退行性疾病。根据第一次共识会议，CTE 的主要神经病理学病变之一是灰质脑沟深度过度磷酸化 tau 蛋白的积累。尸检 CTE 研究还报告了髓磷脂缺失、轴突损伤和白质变性。目前，CTE 的诊断仅限于死后神经病理学分析。我们假设高空间分辨率先进扩散 MRI 可能有助于检测与灰质 tau 病理直接相邻的白质微结构变化。为了检验这一假设，从退伍军人事务部-波士顿大学-脑震荡遗产基金会脑库中获取了 10 名确诊为 CTE 的个体的上额叶皮质的福尔马林固定的死后组织块。使用华盛顿大学的 11.74 T MRI 扫描仪以 250 x 250 x 500 A mu m(3) 空间分辨率获取高级扩散 MRI 数据。以盲法进行扩散张量成像、扩散峰度成像和广义 q 采样成像分析。 MRI 采集后，对组织切片进行脑沟灰质磷酸化 tau 免疫反应性测试。使用髓磷脂黑金染色的二维傅立叶变换分析来评估底层白质的轴突破坏。应用稳健的图像共同配准方法来准确量化扩散 MRI 参数与组织病理学之间的关系。我们发现脑沟下方的白质具有高水平的 tau 病理学，髓磷脂黑金傅立叶变换功率相干性显着受损，表明轴突微结构破坏（r = -0.55，p = 0.0015）。使用扩散张量 MRI，我们发现分数各向异性 (FA) 与轴突破坏有适度 (r = 0.53) 但显着 (p = 0.0012) 相关，其中较低的 FA 与紧邻过度磷酸化 tau 阳性脑沟的白质中较大的轴突破坏相关。总之，我们的研究结果表明轴突破坏和 tau 病理学密切相关，高空间分辨率离体扩散 MRI 有可能检测 CTE 组织中观察到的微观结构变化。未来的研究需要确定这种方法是否可以应用于活人。
Chronic traumatic encephalopathy (CTE) is a progressive degenerative disorder associated with repetitive traumatic brain injury. One of the primary defining neuropathological lesions in CTE, based on the first consensus conference, is the accumulation of hyperphosphorylated tau in gray matter sulcal depths. Post-mortem CTE studies have also reported myelin loss, axonal injury and white matter degeneration. Currently, the diagnosis of CTE is restricted to post-mortem neuropathological analysis. We hypothesized that high spatial resolution advanced diffusion MRI might be useful for detecting white matter microstructural changes directly adjacent to gray matter tau pathology. To test this hypothesis, formalin-fixed post-mortem tissue blocks from the superior frontal cortex of ten individuals with an established diagnosis of CTE were obtained from the Veterans Affairs-Boston University-Concussion Legacy Foundation brain bank. Advanced diffusion MRI data was acquired using an 11.74 T MRI scanner at Washington University with 250 x 250 x 500 A mu m(3) spatial resolution. Diffusion tensor imaging, diffusion kurtosis imaging and generalized q-sampling imaging analyses were performed in a blinded fashion. Following MRI acquisition, tissue sections were tested for phosphorylated tau immunoreactivity in gray matter sulcal depths. Axonal disruption in underlying white matter was assessed using two-dimensional Fourier transform analysis of myelin black gold staining. A robust image co-registration method was applied to accurately quantify the relationship between diffusion MRI parameters and histopathology. We found that white matter underlying sulci with high levels of tau pathology had substantially impaired myelin black gold Fourier transform power coherence, indicating axonal microstructural disruption (r = -0.55, p = 0.0015). Using diffusion tensor MRI, we found that fractional anisotropy (FA) was modestly (r = 0.53) but significantly (p = 0.0012) correlated with axonal disruption, where lower FA was associated with greater axonal disruption in white matter directly adjacent to hyperphosphorylated tau positive sulci. In summary, our findings indicate that axonal disruption and tau pathology are closely associated, and high spatial resolution ex vivo diffusion MRI has the potential to detect microstructural alterations observed in CTE tissue. Future studies will be required to determine whether this approach can be applied to living people.