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）：最近参加伊拉克和阿富汗冲突的军事人员经常暴露于炸弹和其他装置发出的爆炸力（初级爆炸）。临床医生和专家已经制定了诊断轻度 TBI 的最低症状标准，包括感觉改变（例如感到头晕和困惑）、意识丧失 (LOC) 以及暴露于爆炸或撞击后的健忘症。弥散张量成像 (DTI) 已证明这些症状与白质损伤有关。然而，很少有人关注无症状暴露于重复爆炸后的白质研究。与此相关的是，最近的几项研究报告称，尽管没有脑震荡症状，但精英运动员在重复撞击后会出现脑白质损伤。我们的目标是评估近期初次接触爆炸但没有 TBI（亚震荡爆炸暴露）临床症状的军事人员的白质损伤和认知能力受损。爆炸动物模型支持白质损伤的系统机制，例如神经炎症和神经毒性过程，可能导致受影响个体之间空间异质性的弥漫性和广泛的组织损伤。我们将使用比传统体素或感兴趣区域方法更敏感的方法来量化白质损伤的空间异质损伤。我们预计，亚震荡冲击波暴露组和轻度 TBI 组的白质损伤将明显大于未暴露于冲击波的受试者。我们将使用机器学习方法来概括有关临床确诊的轻度 TBI 病例中白质大小的知识。然后，我们将测试这些知识（验证），以便对新病例做出诊断预测，特别是缺乏 TBI 临床诊断的爆炸暴露个体。我们将评估白质空间分布损伤与其他指标之间的关联，包括灰质体积、静息状态功能连接、认知表现以及 PTSD 和抑郁症状。如果我们证实了我们的关键预测，即亚震荡冲击波暴露导致组织损伤、认知障碍和功能性生活质量变化，那么就需要加强现有的方法，通过基于神经影像的诊断来对轻度 TBI 进行基于临床症状的诊断标准。结果进一步表明，许多患有慢性症状（例如情绪症状、疲劳、注意力不集中）的爆炸暴露个体在没有 TBI 急性临床诊断的情况下被错误地诊断为其他疾病（例如抑郁症、创伤后应激障碍）。对我们的方法进行大规模验证，包括转化为民用亚震荡暴露（例如运动），将支持在临床环境中实施先进的扩散成像和分析技术。