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: 7886493
• 负责人: Pratik Mukherjee
• 金额: $ 40.79万
• 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/7886493
• 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; 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; public health relevance; 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岁以下美国人的死亡和残疾的主要原因，在全球范围内正在增加。神经影像学技术，例如计算机断层扫描（CT）或磁共振成像（MRI）是急性TBI临床管理的重要诊断工具。但是，急性TBI中CT或MRI检测到的局灶性病变，例如挫伤和轴突剪切损伤，通常无法预测TBI后的长期功能障碍，尤其是在轻度病例中。该研究建议的目的是建立定量的宏观结构和微结构成像生物标志物，以预测轻度TBI后患者的结果。宏结构生物标志物使用基于变形的形态计量学（DBM）测量局部局部萎缩，该局部脑萎缩3D MR扫描的串行高分辨率3D MR。微结构生物标志物测量基于串行扩散张量成像（DTI）的定量纤维跟踪，在白质完整性下进行创伤后的降低。一百个温和的TBI患者将在受伤后1个月，受伤后6个月，然后在受伤后1年再次在3台特斯拉MR扫描仪上进行高分辨率3D结构MRI和DTI。比较将与40岁，性别和教育匹配的健康对照对象的相同成像协议进行比较。所有受试者将在与MRI/DTI扫描的同一时间点进行神经认知和功能结果测试。 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.这些宏观结构和微结构成像生物标志物也将分别与fMRI和3D MR光谱成像分别与功能和代谢成像数据相关。如果拟议的研究成功地建立了TBI中长期结局的这些定量宏观结构和微结构成像，那么它们有可能作为临床干预试验的替代端点。它们还可能产生内型型，以研究TBI后结果恶化的遗传敏感性因素。为此，在这项研究中，将向患者养育DNA进行基因型分析。具体而言，我们将研究APOE基因型是否影响区域脑萎缩和微结构白质损伤的程度。已知APOE的等位基因变体在TBI之后调节临床结果，这项研究将确定DBM和DTI是否可以提供“中间表型”，从而对APOE基因型对TBI结果的影响。公共卫生相关性：这项研究建议的目的是将两种新的高级磁共振成像（MRI）技术应用于轻度创伤性脑损伤患者的研究：（1）基于变形的形态计量学和（2）扩散张量张量成像。这项研究可能会提高对脑损伤的科学理解，并改善患有脑震荡长期影响的患者的诊断。