Macrostructural and Microstructural Imaging Biomarkers of Traumatic Brain Injury

脑外伤的宏观结构和微观结构成像生物标志物

• 批准号: 8319731
• 负责人: Pratik Mukherjee
• 金额: $ 4.92万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8319731
• 关键词: Accounting; Acute; Affect; Age; American; Amnesia; Anisotropy; Anterior; Apolipoprotein E; Atrophic; Attention; Behavioral; Biological Markers; Brain Concussion; Brain Injuries; Brain Mapping; Brain scan; Cause of Death; Clinical; Clinical Management; Cognitive; Contusions; DNA; Data; Diagnosis; Diagnostic; Diffusion Magnetic Resonance Imaging; Doctor of Medicine; Doctor of Philosophy; Education; Educational Status; Fiber; Functional Magnetic Resonance Imaging; Gender; Genetic Predisposition to Disease; Genetic Variation; Genotype; Glasgow Coma Scale; Health; Image; Imaging technology; Individual; Injury; Intervention Trial; Investigation; Lesion; Long-Term Effects; Magnetic Resonance; Magnetic Resonance Imaging; Measures; Memory; Memory impairment; Metabolic; Monitor; Nerve Degeneration; Neurocognitive; Outcome; Patients; Phenotype; Play; Post-Concussion Syndrome; Prevalence; Principal Investigator; Protocols documentation; Rehabilitation therapy; Research; Research Proposals; Resolution; Role; Scanning; Scientific Advances and Accomplishments; Severities; Shapes; Surrogate Endpoint; Susceptibility Gene; TBI Patients; Techniques; Testing; Therapeutic Intervention; Time; Traumatic Brain Injury; Unconscious State; Weight; X-Ray Computed Tomography; base; brain volume; cerebral atrophy; cohort; disability; endophenotype; follow-up; functional disability; functional outcomes; gray matter; improved; magnetic resonance spectroscopic imaging; memory process; morphometry; neurocognitive test; neuroimaging; processing speed; prognostic; programs; spectroscopic imaging; tool; white matter; white matter damage; white matter injury

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: The objective of this research proposal is to apply two new advanced magnetic resonance imaging (MRI) technologies to the study of patients with mild traumatic brain injury: (1) deformation-based morphometry, and (2) diffusion tensor imaging. This research may advance the scientific understanding of brain injury as well as improve the diagnosis of patients suffering from the long-term effects of concussion.

描述（由申请人提供）：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，并且在全球范围内发病率不断增加。神经影像学技术，如计算机断层扫描（CT）或磁共振成像（MRI）是重要的诊断工具，急性TBI的临床管理。然而，在急性TBI中通过CT或MRI检测到的局灶性病变，例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。本研究的目的是建立定量的宏观和微观结构成像生物标志物，用于预测轻度TBI后患者的预后。宏观结构生物标志物使用脑的连续高分辨率3D MR扫描的基于变形的形态测量（DBM）来测量创伤后局灶性萎缩。微结构生物标志物使用基于连续扩散张量成像（DTI）的定量纤维追踪来测量创伤后白色物质完整性的减少。100名轻度TBI患者将在伤后1个月、伤后6个月和伤后1年在3 Tesla MR扫描仪上接受高分辨率3D结构MRI和DTI。将在40名年龄、性别和教育程度匹配的健康对照受试者中与相同的成像方案进行比较。所有受试者将在MRI/DTI扫描的相同时间点接受神经认知和功能结局检查。在控制损伤严重程度的临床指标（包括格拉斯哥昏迷量表、无意识持续时间和创伤后遗忘持续时间）后，将检验以下假设：通过连续MRI的DBM和/或连续DTI上的进行性白色微结构损伤检测到的进行性局灶性萎缩的空间范围增加与损伤后1年的神经认知和功能结局恶化相关。这些宏观结构和微观结构成像生物标志物也将分别与使用fMRI和3D MR光谱成像的功能和代谢成像数据相关联。如果拟议的研究成功地建立了TBI长期结局的这些定量宏观结构和微观结构成像生物标志物，那么它们可能作为临床干预试验的替代终点。他们也可能产生内表型的遗传易感性因素的研究，TBI后恶化的结果。为此，将从本研究中的患者中储存DNA用于基因型分析。具体而言，我们将研究ApoE基因型是否影响局部脑萎缩和微结构白色物质损伤的程度。已经知道ApoE的等位基因变体调节TBI后的临床结果，并且本研究将确定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”。公共卫生相关性：本研究计划的目的是将两种新的先进磁共振成像（MRI）技术应用于轻度创伤性脑损伤患者的研究：（1）基于变形的形态测量学，和（2）扩散张量成像。这项研究可能会促进对脑损伤的科学认识，并改善对脑震荡长期影响患者的诊断。