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

基本信息

批准号：
8089234
负责人：
Pratik Mukherjee
金额：
$ 41.29万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
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/8089234
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

项目摘要

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，并且在全球范围内患病率不断上升。计算机断层扫描 (CT) 或磁共振成像 (MRI) 等神经影像技术是急性 TBI 临床治疗的重要诊断工具。然而，在急性 TBI 中通过 CT 或 MRI 检测到的局灶性病变，例如挫伤和轴突剪切损伤，通常不能预测 TBI 后的长期功能障碍，特别是在轻度病例中。本研究计划的目的是建立定量的宏观结构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基于变形的大脑连续高分辨率 3D MR 扫描的形态测量 (DBM) 来测量创伤后局灶性萎缩。微观结构生物标志物使用基于串行扩散张量成像 (DTI) 的定量纤维追踪来测量创伤后白质完整性的下降。 100 名轻度 TBI 患者将在受伤后 1 个月、受伤后 6 个月以及受伤后 1 年在 3 台 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对相同的成像方案进行比较。所有受试者将在 MRI/DTI 扫描的同一时间点接受神经认知和功能结果测试。该假设将得到检验，在控制了临床测量后，连续 MRI 的 DBM 检测到的进行性局灶性萎缩和/或连续 DTI 上的进行性白质微结构损伤的空间范围的增加与损伤后一年较差的神经认知和功能结果相关。伤害严重程度，包括格拉斯哥昏迷量表、意识丧失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还将分别使用 fMRI 和 3D MR 光谱成像与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 长期结果的定量宏观结构和微观结构成像生物标志物，那么它们有可能作为临床干预试验的替代终点。它们还可能产生内表型，用于研究导致 TBI 后预后恶化的遗传易感因素。为此，本研究中将从患者身上收集 DNA 进行基因型分析。具体来说，我们将检查ApoE基因型是否影响区域性脑萎缩和微结构白质损伤的程度。已知 ApoE 等位基因变异可调节 TBI 后的临床结果，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”。公共健康相关性：本研究提案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，以及 (2) 弥散张量成像。这项研究可能会增进对脑损伤的科学认识，并改善对遭受脑震荡长期影响的患者的诊断。