Quantitative assessments of traumatic axonal injury in human brain: concordance of microdialysis and advanced MRI
Quantitative assessments of traumatic axonal injury in human brain: concordance of microdialysis and advanced MRI
复制标题
DOI：
10.1093/brain/awv152
复制
发表时间：
2015-08-01
期刊：
影响因子：
14.5
通讯作者：
Brody, David L.
中科院分区：
文献类型：
--
作者：
Magnoni, Sandra;Mac Donald, Christine L.;Brody, David L.
轴突损伤是脑外伤后不良后果的主要原因。然而，目前无法可靠地评估活人的轴突损伤程度。在这里，我们在同一队列的 15 名严重创伤性脑损伤患者中使用了两种具有不同噪声源和局限性的实验方法来评估轴突损伤。损伤后平均时间为 17 小时（13-29 小时），在所有患者的正常外观（计算机断层扫描）额叶白质中植入 100 千道尔顿截止微透析导管，并采集样本至少 72 小时。每 1-2 小时测量一次微透析样品中的多种分析物，例如代谢标记物葡萄糖、乳酸、丙酮酸、谷氨酸、tau 蛋白和淀粉样蛋白。 11 名患者在受伤后 2-9 周进行了 3 T 的弥散张量磁共振成像扫描。弥散张量成像结果的稳定性通过 1-3 年后对 7 名患者的重复扫描得到验证。另外四名患者仅在受伤后 1-3 年接受扫描。通过与每位患者的 5 名健康对照受试者进行比较来评估影像异常，并按年龄和性别进行匹配（总共 32 名对照）。在微透析或扫描过程中没有出现安全问题。我们发现，对大脑细胞外空间中轴突细胞骨架蛋白 tau 的急性微透析测量与基于扩散张量磁共振成像的对微透析导管插入位点附近 1 厘米半径白质遮蔽区域中脑白质完整性降低的测量具有良好的相关性。具体来说，我们发现与健康对照相比，微透析测量的损伤后 13-36 小时 tau 水平与各向异性降低之间存在显着的负相关（Spearman's r = -0.64，P = 0.006）。微透析导管插入部位附近的各向异性减少与多个额外白质区域的减少高度相关。我们将此结果解释为意味着微透析和扩散张量磁共振成像都准确地反映了相同的病理生理过程：创伤性轴突损伤。这种交叉验证增加了对轴突损伤临床评估的两种方法的信心。然而，微透析和扩散张量磁共振成像均未通过人体死后组织学验证。此外，未来的工作需要确定这些创伤性轴突损伤评估与其他临床和放射学措施相结合的预后意义。
Axonal injury is a major contributor to adverse outcomes following brain trauma. However, the extent of axonal injury cannot currently be assessed reliably in living humans. Here, we used two experimental methods with distinct noise sources and limitations in the same cohort of 15 patients with severe traumatic brain injury to assess axonal injury. One hundred kilodalton cut-off microdialysis catheters were implanted at a median time of 17 h (13-29 h) after injury in normal appearing (on computed tomography scan) frontal white matter in all patients, and samples were collected for at least 72 h. Multiple analytes, such as the metabolic markers glucose, lactate, pyruvate, glutamate and tau and amyloid-beta proteins, were measured every 1-2 h in the microdialysis samples. Diffusion tensor magnetic resonance imaging scans at 3 T were performed 2-9 weeks after injury in 11 patients. Stability of diffusion tensor imaging findings was verified by repeat scans 1-3 years later in seven patients. An additional four patients were scanned only at 1-3 years after injury. Imaging abnormalities were assessed based on comparisons with five healthy control subjects for each patient, matched by age and sex (32 controls in total). No safety concerns arose during either microdialysis or scanning. We found that acute microdialysis measurements of the axonal cytoskeletal protein tau in the brain extracellular space correlated well with diffusion tensor magnetic resonance imaging-based measurements of reduced brain white matter integrity in the 1-cm radius white matter-masked region near the microdialysis catheter insertion sites. Specifically, we found a significant inverse correlation between microdialysis measured levels of tau 13-36 h after injury and anisotropy reductions in comparison with healthy controls (Spearman's r = -0.64, P = 0.006). Anisotropy reductions near microdialysis catheter insertion sites were highly correlated with reductions in multiple additional white matter regions. We interpret this result to mean that both microdialysis and diffusion tensor magnetic resonance imaging accurately reflect the same pathophysiological process: traumatic axonal injury. This cross-validation increases confidence in both methods for the clinical assessment of axonal injury. However, neither microdialysis nor diffusion tensor magnetic resonance imaging have been validated versus post-mortem histology in humans. Furthermore, future work will be required to determine the prognostic significance of these assessments of traumatic axonal injury when combined with other clinical and radiological measures.