Objective:Determine associations between cognitive outcomes in remote TBI (i.e., at least 6 months post injury), a blood marker of neural degeneration (i.e., Tau), and diffusion kurtosis imaging (DKI) measures (e.g., mean or radial kurtosis). Because DKI imaging is sensitive to the environmental complexity of the imaged area, we sought to investigate regions known to be associated with the cognitive and emotional sequalae of TBI, such as the anterior thalamic radiations, uncinate fasciculus, and the corpus callosum.Participants and Methods:41 individuals with mild-to-moderate TBI and a mean age(SD) of 36.1(10.4) years underwent DKI, a blood draw, and neuropsychological assessments. 23 healthy controls (HC) with a mean age(SD) of 35.2(15.2) years underwent the blood draw and assessments, but no imaging. Higher diffusion kurtosis indicates more restricted diffusion, possibly due to greater complexity within the imaged region. Thus, in the context of TBI, DKI can be used as a proxy measurement for biological processes that alter the complexity of imaged environments, such as reactive gliosis. Some people show cognitive deficits long after TBI and this could be associated with increased inflammation and membrane protein aggregates in damaged brain regions. We used bivariate correlations and general linear models to investigate the association of mean kurtosis (MK) in long white matter tracts and Tau (total or phosphorylated) to color-word Stroop scores; a measure of fronto-subcortical function.Results:In patients with TBI, MK was significantly associated with serum total Tau (TTau) in the right (r=-0.396) and left (r=-0.555) uncinate fasciculus (UF), right (r=-0.402) and left (r=-0.504) anterior thalamic radiations (ATR), and the genu (r=-0.526) and body (r=-0.404) of the corpus callosum (CC). TTau had a significant association with word Stroop scores, F(1,63)=-2.546, p=0.013. However, there was no significant effect of group (i.e., TBI or HC), F(2,63)=-0.426, p=0.672, on cognitive performance. When models were implemented that included both TTau and MK in either the UF or ATR as explanatory variables to predict word Stroop scores, TTau levels and MK in the right UF explained a significant amount of the variance in Stroop performance, F(1,29)=2.215, p=0.025. Further, there was also a significant association between radial kurtosis in the right UF and Stroop word scores (r= 0.366).Conclusions:Our results show that an indicator of biological complexity (DKI) in cognitively important brain regions is associated with cognitive performance and Tau in patients with remote mild-to-moderate TBI. The UF is a critical fronto-temporal/subcortical pathway that has previously been implicated in the manifestation of executive dysfunction and mood dysregulation in TBI. Tau is an important marker of neurodegeneration implicated in Alzheimer’s disease, Parkinson’s disease, and chronic traumatic encephalopathy (CTE), and DKI is potentially sensitive to markers of neurodegeneration. The association of Tau and DKI measures is novel and shows concordance between blood and brain imaging markers and cognitive performance in patients with mild to moderate TBI.

中文翻译：

---

25 扩散峭度成像、Tau 和 TBI 认知结果之间的关联

目的：确定远程 TBI（即受伤后至少 6 个月）的认知结果、神经变性的血液标志物（即 Tau）和扩散峰度成像 (DKI) 测量（例如平均或径向峰度）之间的关联。由于 DKI 成像对成像区域的环境复杂性很敏感，因此我们试图研究已知与 TBI 认知和情感后遗症相关的区域，例如丘脑前辐射、钩束和胼胝体。 参与者和方法：41 名患有轻度至中度 TBI 且平均年龄 (SD) 为 36.1(10.4) 岁的个体接受了 DKI、抽血和神经心理学评估。23 名平均年龄（SD）为 35.2（15.2）岁的健康对照（HC）接受了抽血和评估，但没有进行影像学检查。扩散峰度越高表示扩散越受限，这可能是由于成像区域内的复杂性更大。因此，在 TBI 的背景下，DKI 可以用作改变成像环境复杂性的生物过程的替代测量，例如反应性神经胶质增生。有些人在创伤性脑损伤后很久就表现出认知缺陷，这可能与受损大脑区域的炎症增加和膜蛋白聚集有关。我们使用双变量相关性和一般线性模型来研究长白质束中的平均峰度 (MK) 和 Tau（总或磷酸化）与颜色词 Stroop 评分的关联；结果：在 TBI 患者中，MK 与右侧 (r=-0.396) 和左侧 (r=-0.555) 的血清总 Tau (TTau) 显着相关。 (r=-0.402) 和左 (r=-0.504) 前丘脑辐射 (ATR)，以及胼胝体 (CC) 的膝部 (r=-0.526) 和胼胝体 (r=-0.404)。TTau 与单词 Stroop 分数有显着相关性，F(1,63)=-2.546，p=0.013。然而，组别（即 TBI 或 HC）对认知表现没有显着影响，F(2,63)=-0.426，p=0.672。当实施模型时，在 UF 或 ATR 中同时包含 TTau 和 MK 作为解释变量来预测单词 Stroop 分数，右侧 UF 中的 TTau 水平和 MK 解释了 Stroop 表现中的大量方差，F(1,29) =2.215，p=0.025。此外，右侧 UF 的径向峰度与 Stroop 单词得分之间也存在显着相关性 (r= 0.366)。结论：我们的结果表明，认知重要脑区的生物复杂性 (DKI) 指标与认知表现和认知能力相关。患有远期轻至中度 TBI 的患者中的 Tau 蛋白。UF 是一条重要的额颞叶/皮质下通路，此前曾被认为与 TBI 中执行功能障碍和情绪失调的表现有关。Tau 蛋白是与阿尔茨海默病、帕金森病和慢性创伤性脑病 (CTE) 相关的神经退行性变的重要标志物，DKI 对神经退行性变标志物可能敏感。Tau 和 DKI 测量值之间的关联是新颖的，并且显示了轻度至中度 TBI 患者的血液和脑成像标志物与认知表现之间的一致性。