The contribution of gliosis to diffusion tensor anisotropy and tractography following traumatic brain injury: validation in the rat using Fourier analysis of stained tissue sections
The contribution of gliosis to diffusion tensor anisotropy and tractography following traumatic brain injury: validation in the rat using Fourier analysis of stained tissue sections
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DOI：
10.1093/brain/awr161
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发表时间：
2011-08-01
期刊：
影响因子：
14.5
通讯作者：
Frank, Joseph A.
中科院分区：
文献类型：
--
作者：
Budde, Matthew D.;Janes, Lindsay;Frank, Joseph A.
弥散张量成像对大脑微观结构的完整性高度敏感，并发现了其他方法无法识别的创伤性脑损伤后的显着异常。希望这种增加的敏感性将有助于创伤性损伤患者的检测和预测。然而，人们对这种变化的病理基础知之甚少。具体而言，源自扩散张量成像的分数各向异性的减少与白质纤维中的轴突损伤、髓磷脂损伤或两者一致。相比之下，在人类和动物模型中，各向异性分数的增加被认为反映了轴突再生和可塑性，但这种变化的直接组织学证据仍然很薄弱。我们开发了一种使用傅立叶分析量化染色组织切片的各向异性的方法，并将该方法应用于大鼠控制的皮质冲击模型，以识别引起亚急性至慢性创伤性脑损伤的扩散张量成像变化的特定病理特征。进行多元线性回归以将组织学测量结果与测量的扩散张量变化联系起来。结果表明，受伤后受损皮层的各向异性显着增加（P < 0.001）。皮质各向异性与反应性星形胶质细胞的连贯组织（即神经胶质细胞增生）独立相关（标准化β = 0.62，P = 0.04），并且不归因于轴突。相比之下，白质各向异性的减少（P < 0.001）与脱髓鞘显着相关（β = 0.75，P = 0.0015），并且在较小程度上与轴突变性相关（β = -0.48，P = 0.043）。受损皮质内的神经胶质增生也影响了扩散张量纤维束成像，强调了这样一个事实：受伤大脑中的虚假纤维束不一定反映连续的轴突，而可能描绘神经胶质疤痕。目前的研究展示了一种将病理学与扩散张量成像结果联系起来的新方法，阐明了创伤性脑损伤后各向异性变化的潜在机制，并显着影响了受伤大脑中扩散张量成像结果的临床解释。
Diffusion tensor imaging is highly sensitive to the microstructural integrity of the brain and has uncovered significant abnormalities following traumatic brain injury not appreciated through other methods. It is hoped that this increased sensitivity will aid in the detection and prognostication in patients with traumatic injury. However, the pathological substrates of such changes are poorly understood. Specifically, decreases in fractional anisotropy derived from diffusion tensor imaging are consistent with axonal injury, myelin injury or both in white matter fibres. In contrast, in both humans and animal models, increases in fractional anisotropy have been suggested to reflect axonal regeneration and plasticity, but the direct histological evidence for such changes remains tenuous. We developed a method to quantify the anisotropy of stained histological sections using Fourier analysis, and applied the method to a rat controlled cortical impact model to identify the specific pathological features that give rise to the diffusion tensor imaging changes in subacute to chronic traumatic brain injury. A multiple linear regression was performed to relate the histological measurements to the measured diffusion tensor changes. The results show that anisotropy was significantly increased (P < 0.001) in the perilesioned cortex following injury. Cortical anisotropy was independently associated (standardized beta = 0.62, P = 0.04) with the coherent organization of reactive astrocytes (i.e. gliosis) and was not attributed to axons. By comparison, a decrease in white matter anisotropy (P < 0.001) was significantly related to demyelination (beta = 0.75, P = 0.0015) and to a lesser extent, axonal degeneration (beta = -0.48, P = 0.043). Gliosis within the lesioned cortex also influenced diffusion tensor tractography, highlighting the fact that spurious tracts in the injured brain may not necessarily reflect continuous axons and may instead depict glial scarring. The current study demonstrates a novel method to relate pathology to diffusion tensor imaging findings, elucidates the underlying mechanisms of anisotropy changes following traumatic brain injury and significantly impacts the clinical interpretation of diffusion tensor imaging findings in the injured brain.