White Matter Damage in Subconcussive Blast Exposure

描述(由申请人提供)：最近在伊拉克和阿富汗冲突中的军事人员中，暴露于炸弹和其他装置发出的爆炸力(初级爆炸)是很常见的。临床医生和专家已经建立了诊断轻度脑损伤的最低症状标准，包括感觉改变(例如，感到头晕和困惑)、意识丧失(LOC)和暴露在冲击波或撞击后的健忘症。扩散张量成像(DTI)显示这些症状与脑白质损伤有关。然而，很少有人注意研究无症状的重复冲击波暴露后的脑白质。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，但精英运动员在反复撞击后脑白质受损。我们的目标是评估近期没有临床症状的脑震荡(亚震荡冲击波)暴露的初级冲击波暴露的军事人员的白质损害和认知能力损害。冲击波的动物模型支持白质损伤的系统机制，如神经炎性和神经毒性过程，这些过程可能导致弥漫性和广泛性组织损伤，在受影响的个体中存在空间上的异质性。我们将使用比传统的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性损伤。我们预计，亚震荡冲击波暴露组和轻度颅脑损伤组的脑白质损伤相似，将明显大于冲击波未暴露组。我们将使用机器学习方法来概括临床上已确诊的轻度脑外伤患者脑白质大小的知识。然后，我们将测试这一知识(验证)，以对新病例做出诊断预测，特别是对缺乏脑损伤临床诊断的爆炸性接触者。我们将评估白质的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、认知表现以及创伤后应激障碍和抑郁的症状。如果我们证实了我们的关键预测，即亚震荡冲击波暴露会导致组织损伤、认知障碍和功能生活质量变化，那么就有理由加强现有的方法，即用基于神经影像的诊断标准对轻度脑外伤进行基于临床症状的诊断。这一结果将进一步暗示，许多有慢性症状(如情绪症状、疲劳、注意力不集中)的冲击波暴露者，在没有急性脑损伤临床诊断的情况下，被误诊为其他疾病(如抑郁症、创伤后应激障碍)。大规模验证我们的方法，包括转换为民用亚震荡暴露(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。

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.