White Matter Damage in Subconcussive Blast Exposure

亚震荡爆炸中的白质损伤

基本信息

批准号：
8815240
负责人：
RAJENDRA A MOREY
金额：
$ 34.42万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8815240
关键词：
Acute Affect Afghanistan Amnesia Animal Model Attention Blast Cell Brain Chronic Climacteric Clinical Cognitive Conflict (Psychology)Conscious Data Devices Diagnosis Diagnostic Diffuse Diffusion Diffusion Magnetic Resonance Imaging Dose Exposure to Fatigue Feeling Frequencies Goals Heterogeneity Human Image Impaired cognition Impairment Individual Injury Iraq Kinetics Knowledge Location Machine Learning Measures Mechanics Mental Depression Methods Military Personnel Moods Pattern Performance Post-Traumatic Stress Disorders Process Quality of life Reliance Reporting Rest Sports Structure Symptoms System Techniques Testing Tissues Translations Traumatic Brain Injury Unconscious State Validation base brain tissue clinical Diagnosis executive function gray matter inattention interest meetings neuroimaging neurotoxic novel public health relevance response white matter white matter damage

项目摘要

DESCRIPTION (provided by applicant): Exposure to explosive forces (primary blast) emanating from bombs and other devices is common in recent military personnel from the conflicts in Iraq and Afghanistan. Clinicians and experts have established minimum symptom criteria for diagnosis of mild TBI including altered sensorium (e.g. feeling dazed and confused), loss of consciousness (LOC), and amnesia following exposure to blast or impact. Diffusion Tensor Imaging (DTI) has demonstrated that these symptoms are associated with white matter damage. However, little attention has been given to investigating white matter following asymptomatic exposure to repetitive blast. Relatedly, several recent studies report white matter damage in elite athletes following repetitive impacts despite the absence of concussive symptoms. Our goal is to assess damage to white matter and impairments in cognitive performance in recent military personnel with primary blast exposure without clinical symptoms of TBI (subconcussive blast exposure). Animal models of blast support systemic mechanisms of white matter damage such as neuroinflammatory and neurotoxic processes that are likely to result in diffuse and widespread tissue injury that is spatially heterogeneous among affected individuals. We will use methods for quantifying spatially heterogeneous damage to white matter damage that are more sensitive than conventional voxelwise or region-of-interest approaches. We anticipate comparable white matter damage in a subconcussive blast exposed group and a mild TBI group that will be significantly greater than in blast- unexposed subjects. We will use a machine learning approach to generalize knowledge about the magnitude of white matter in clinically established cases of mild TBI. We will then test this knowledge (validation) to make diagnostic predictions for new cases, particularly blast-exposed individuals, who lack a clinical diagnosis of TBI. We will assess the association between spatially distributed injury to white matter and other measures including, gray matter volume, resting-state functional connectivity, cognitive performance, and symptoms of PTSD and depression. If we confirm our key predictions that tissue damage, cognitive impairment, and functional quality of life changes result from subconcussive blast exposure, it would argue for an augmentation of the established approach for making clinical symptom-based diagnoses of mild TBI with neuroimaging-based diagnostic criteria. The results would further imply that many blast-exposed individuals with chronic symptoms (e.g. mood symptoms, fatigue, inattention) are being incorrectly diagnosed with other conditions (e.g. depression, PTSD) in the absence of acute clinical diagnosis of TBI. Validation of our approach on a large scale including translation to civilian subconcussive exposure (e.g. sports), would argue for implementing advanced diffusion imaging and analytic techniques in the clinical setting.

描述（由申请人提供）：在伊拉克和阿富汗冲突的最近军事人员中，来自炸弹和其他设备发出的爆炸力（主要爆炸）很常见。临床医生和专家已经建立了诊断为轻度TBI的最低症状标准，包括改变的感觉（例如，昏昏欲睡和困惑），意识丧失（LOC）和失忆症在暴露于爆炸或撞击之后的失忆症。扩散张量成像（DTI）表明这些症状与白质损伤有关。但是，在无症状暴露于重复性爆炸后，很少关注研究白质。相关的是，最近的一些研究报告说，尽管没有脑震荡症状，但精英运动员对精英运动员的损害。我们的目标是评估最近一次军事人员暴露的军事人员对白质的损害和认知表现损害，而没有TBI的临床症状（亚语爆炸暴露）。爆炸的动物模型支持白质损伤的全身机制，例如神经炎症和神经毒性过程，这些过程可能导致受影响个体之间在空间上是异构性异构的弥漫性和广泛的组织损伤。我们将使用方法来量化对白质损伤的空间异质损害，这些损害比传统的voxelwise或利益区域方法更敏感。我们预计在亚语爆炸型组和一个轻度的TBI组中会明显大于爆炸未暴露受试者，这会有可比的白质损害。我们将使用一种机器学习方法来概括一下在临床上建立的轻度TBI病例中有关白质的大小的知识。然后，我们将测试此知识（验证），以对缺乏TBI临床诊断的新病例，尤其是暴露的个体进行诊断预测。我们将评估空间分布的对白质的损伤与其他措施之间的关联，包括灰质体积，静止状态功能连通性，认知性能以及PTSD和抑郁症的症状。如果我们确认组织损害，认知障碍和生活质量的关键预测是由于亚语爆炸暴露而导致的，它将主张增强基于神经影像学诊断标准的基于临床症状的轻度TBI诊断的已建立方法。结果将进一步表明，在没有TBI急性临床诊断的情况下，许多患有慢性症状（例如情绪症状，疲劳，烦恼）的人都被错误地诊断出患有其他疾病（例如抑郁症，PTSD）。大规模验证我们的方法，包括转化为平民亚语暴露（例如运动），将主张在临床环境中实施先进的扩散成像和分析技术。