White Matter Damage in Subconcussive Blast Exposure

亚震荡爆炸中的白质损伤

• 批准号: 9124954
• 负责人: RAJENDRA A MOREY
• 金额: $ 34.78万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 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/9124954
• 关键词: Acute; Affect; Afghanistan; Amnesia; Animal Model; Attention; Blast Cell; Brain; Climacteric; Clinical; Conflict (Psychology); Conscious; Data; Devices; Diagnosis; Diagnostic; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Dose; Exposure to; Fatigue; Feeling; Frequencies; Goals; Health; Heterogeneity; Human; Image; Impaired cognition; Impairment; Individual; Injury; Iraq; Kinetics; Knowledge; Location; Machine Learning; Measures; Mechanics; Mental Depression; Methods; Military Personnel; Pattern; Performance; Post-Traumatic Stress Disorders; Process; Quality of life; Reporting; Rest; Sports; Structure; Symptoms; System; Techniques; Testing; Tissues; Translations; Traumatic Brain Injury; Unconscious State; Validation; associated symptom; base; brain tissue; clinical Diagnosis; cognitive performance; cognitive task; concussive symptom; executive function; gray matter; inattention; interest; meetings; mild traumatic brain injury; mood symptom; neuroimaging; neuroinflammation; neurotoxic; novel; persistent symptom; response; white matter; white matter damage

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（申请人提供）：暴露于炸弹和其他装置产生的爆炸力（初级爆炸）在最近伊拉克和阿富汗冲突中的军事人员中很常见。临床医生和专家已经建立了诊断轻度TBI的最低症状标准，包括感觉改变（例如感觉眩晕和困惑），意识丧失（意识丧失）和暴露于爆炸或撞击后的健忘症。扩散张量成像（DTI）已证明这些症状与白色物质损害有关。然而，很少有人注意到调查白色物质无症状暴露于重复爆炸。与此相关的是，最近的几项研究报告，尽管没有脑震荡症状，但优秀运动员在重复撞击后仍会出现白色物质损伤。 我们的目标是评估近期军事人员的白色物质损伤和认知能力的损害，这些军事人员主要暴露于冲击波而没有TBI（亚震荡冲击波暴露）的临床症状。 爆炸的动物模型支持白色物质损伤的全身机制，例如神经炎症和神经毒性过程，其可能导致在受影响个体中空间异质的弥漫性和广泛的组织损伤。我们将使用的方法来量化空间异质性损伤的白色物质的损害，比传统的voxelwise或区域的利益的方法更敏感。我们预计，在亚震荡冲击波暴露组和轻度TBI组中，白色损害相当，将显著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病例中白色物质大小的知识。然后，我们将测试这些知识（验证），为新病例做出诊断预测，特别是爆炸暴露的个体，他们缺乏TBI的临床诊断。 我们将评估空间分布的白色物质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、认知表现以及创伤后应激障碍和抑郁症状。如果我们证实了我们的关键预测，即组织损伤，认知障碍和功能性生活质量变化是由亚震荡冲击波暴露引起的，那么我们将主张加强现有的方法，以神经影像学为基础的诊断标准对轻度TBI进行临床诊断。结果将进一步暗示，许多具有慢性症状（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的急性临床诊断的情况下被错误地诊断为其他病症（例如抑郁症、PTSD）。我们的方法在大规模上的验证，包括翻译到民用亚震荡暴露（如体育），将主张在临床环境中实施先进的扩散成像和分析技术。