Macrostructural and Microstructural Imaging Biomarkers of Traumatic Brain Injury

项目摘要 创伤性脑损伤（TBI）是45岁以下美国人死亡和残疾的主要原因， 在全球范围内的流行率不断上升。神经成像技术，如计算机断层扫描（CT）或 磁共振成像（MRI）是用于急性TBI的临床管理的重要诊断工具。 然而，在急性TBI中，CT或MRI发现的局灶性病变，如挫伤和轴索剪切， 损伤，通常不能预测TBI后的长期功能障碍，特别是在轻度病例中。的 本研究的目的是建立定量的宏观和微观结构成像 用于预测轻度TBI后患者结局的生物标志物。宏观结构生物标志物测量后， 创伤性局灶性萎缩，使用基于变形的形态学（DBM）的系列高分辨率3D MR扫描， 大脑微结构生物标志物测量创伤后白色物质完整性的减少， 基于连续扩散张量成像（DTI）的定量纤维追踪。 100名轻度TBI患者将在3特斯拉MR扫描仪上接受高分辨率3D结构MRI和DTI 在伤后1个月，伤后6个月，然后在伤后1年再次进行。进行比较时 在40名年龄、性别和教育程度相匹配的健康对照受试者中进行相同的成像方案。所有 受试者将在与MRI/DTI相同的时间点接受神经认知和功能结局测试 扫描。将检验这一假设，即通过检测进行性局灶性萎缩的空间范围增加， 序列MRI的DBM和/或序列DTI的进行性白色微结构损伤与恶化相关 损伤后1年的神经认知和功能结局，在控制损伤的临床指标后 严重程度包括格拉斯哥昏迷评分、无意识持续时间和创伤后遗忘持续时间。 这些宏观结构和微观结构成像生物标志物也将与功能和生物学特性相关。 分别使用fMRI和3D MR光谱成像的代谢成像数据。 如果拟议的调查成功地建立了这些定量的宏观结构和 TBI长期结果的显微结构成像生物标志物，那么它们可能作为替代物 临床干预试验的终点。它们也可能为遗传学研究提供内在表型。 TBI后恶化结果的易感因素。为了达到这个目的，DNA将从病人的银行 进行基因型分析。具体来说，我们将研究ApoE基因型是否影响 局部脑萎缩程度和显微结构白色损伤。ApoE的等位基因变体是 已经知道DBM和DTI可以调节TBI后的临床结果，这项研究将确定DBM和DTI是否可以 为ApoE基因型对TBI结果的影响提供“中间表型”。

PROJECT SUMMARY Traumatic brain injury (TBI) is the leading cause of death and disability in Americans under age 45, and is increasing in prevalence worldwide. Neuroimaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) are important diagnostic tools for the clinical management of acute TBI. However, the focal lesions detected by CT or MRI in acute TBI, such as contusions and axonal shearing injuries, are often not predictive of long-term functional disability after TBI, especially in mild cases. The objective of this research proposal is to establish quantitative macrostructural and microstructural imaging biomarkers for predicting patient outcome after mild TBI. The macrostructural biomarker measures post- traumatic focal atrophy using deformation-based morphometry (DBM) of serial high-resolution 3D MR scans of the brain. The microstructural biomarker measures post-traumatic decreases in white matter integrity using quantitative fiber tracking based on serial diffusion tensor imaging (DTI). One hundred mild TBI patients will undergo high-resolution 3D structural MRI and DTI on 3 Tesla MR scanners at 1 month after injury, at 6 months after injury, and then again at 1 year after injury. Comparison will be made to the same imaging protocol in 40 age-, gender-, and education-matched healthy control subjects. All subjects will undergo neurocognitive and functional outcome tests at the same time points as the MRI/DTI scans. The hypothesis will be tested that increasing spatial extent of progressive focal atrophy detected by DBM of serial MRI and/or progressive white matter microstructural injury on serial DTI is correlated with worse neurocognitive and functional outcomes at one year after injury, after controlling for clinical measures of injury severity including Glasgow Coma Scale, duration of unconsciousness, and duration of post-traumatic amnesia. These macrostructural and microstructural imaging biomarkers will also be correlated with functional and metabolic imaging data using fMRI and 3D MR spectroscopic imaging, respectively. If the proposed investigation is successful in establishing these quantitative macrostructural and microstructural imaging biomarkers of long-term outcome in TBI, then they could potentially serve as surrogate endpoints for clinical intervention trials. They might also yield endophenotypes for studies of genetic susceptibility factors that worsen outcome after TBI. Towards this purpose, DNA will be banked from patients in this study for genotype analysis. Specifically, we will examine whether ApoE genotype influences the degree of regional brain atrophy and microstructural white matter injury. The allelic variants of ApoE are already known to modulate clinical outcome after TBI, and this study will determine if DBM and DTI can provide "intermediate phenotypes" for the effect of ApoE genotype on TBI outcome.