Diagnosing Mild TBI in VA and Active Duty Military Patients using MEG and DTI

描述(由申请人提供)： 轻度颅脑损伤是退伍军人和现役军人最重要的健康问题之一。颅脑损伤的诊断和监测是VA研究的重点。轻度(和一些中度)脑外伤可能很难诊断，因为在常规的急性神经成像技术(如CT和MRI)上通常看不到损伤。此外，传统的神经成像技术对脑外伤引起的生理改变的敏感性有限，而且对长期结果的预测作用很差。我们的初步研究表明，创伤损伤的神经元组织产生低频电磁信号，功能连通性降低，扩散各向异性降低。建议的研究将使用包括脑磁图(MEG)和弥散张量成像(DTI)在内的综合多模式神经成像方法来诊断和监测轻度脑损伤。这种方法在检测VA和现役军人轻度脑损伤患者中的轻微神经元损伤方面具有比传统成像技术更高的敏感性和特异性。这项拟议的研究有三个具体目标：特定目标1将通过检测常规神经成像方法(如CT和MRI)看不到的神经元损伤(损伤部位和受影响的神经元网络)，探讨综合MEG-DTI方法在VA和现役mTBI患者中的诊断价值。我们的初步数据显示，病理性脑磁图慢波、脑磁图功能连接性降低和DTI各向异性降低是mTBI中组织剪切和拉伸所致轴索损伤的特征，在诊断个别轻度脑外伤患者方面明显优于CT/MRI。具体目的2采用N-back工作记忆(WM)脑磁图任务研究现役军人和VA轻度脑损伤患者认知功能障碍的神经生理学基础。本申请的具体目标3将研究脑震荡后症状、神经心理学检查测量的认知障碍与脑脊液和脑外伤现役患者脑磁图和弥散张量成像测量之间的关系。为了实现这些目标，我们建议开发新的成像分析工具：频域Vestal，用于准确定位病理性MEG慢波；双核波束形成器，用于在低信噪比条件下可靠地使用MEG获得功能连接减少的神经元网络；以及一个平台，用于将灰质中的功能性MEG结果与白质纤维束中的结构性DTI结果相结合。该方法的成功不仅将极大地提高我们通过检测使用传统神经成像技术看不见的微小神经损伤(例如，位置和网络)来诊断轻微脑损伤的能力，而且还将提供神经成像工具和软件，在对VA和现役脑损伤患者进行新的神经药物和/或神经心理治疗的干预前后评估中，神经成像工具和软件潜在地被用作客观评估方法。

DESCRIPTION (provided by applicant): Mild traumatic brain injury (TBI) represents one of the most significant health issues in VA and active duty military patients. Diagnosing and monitoring of TBI are major focuses of VA research. Mild (and some moderate) TBI can be difficult to diagnose because the injuries are generally not visible on conventional acute neuroimaging techniques (e.g., CT and MRI). Furthermore, conventional neuroimaging techniques have limited sensitivity to the physiological alterations due to TBI, and poor predictive utility for long-term outcome. Our preliminary study shows that neuronal tissues injured by trauma generate low frequency electromagnetic signals, decreased functional connectivity, and reduction of diffusion anisotropy. The proposed study will use integrated multi-modality neuroimaging approach involving Magnetoencephalography (MEG) and diffusion tensor imaging (DTI) in diagnosing and monitoring mild TBI. This approach has the potential of attaining higher sensitivity and specificity than conventional imaging techniques in detecting subtle neuronal injuries in mild TBI patients in VA and active duty military patients. There are three specific aims in the proposed study: Specific Aim 1 will investigate the diagnostic value of the integrated MEG-DTI approach in VA and active duty patients with mTBI by detecting neuronal injuries (loci of the injury as well as affected neuronal networks) not visible with conventional neuroimaging methods (e.g., CT and MRI). Our preliminary data show that pathological MEG slow-waves, reduced MEG functional connectivity, and reduced DTI anisotropy are characteristics of axonal injury due to tissue shearing and stretching in mTBI, with markedly better sensitivity than CT/MRI in diagnosing individual mild TBI patients. Specific Aim 2 studies the neurophysiological basis of the cognitive impairments using N-back working memory (WM) MEG task in active duty and VA patients with mild TBI. Specific Aim 3 of the present application will study the relationship between post-concussive symptoms, cognitive deficits as measured by neuropsychological exams, and the neuroimaging measurements with MEG and DTI in VA and active duty patients with mTBI. To achieve these aims, we propose to develop new imaging analysis tools: frequency-domain VESTAL for accurately localizing pathological MEG slow-waves; Dual-core Beamformer for reliably obtaining the neuronal networks with reduced functional connectivity using MEG under the condition of poor signal to noise ratio; and a platform for integrating the functional MEG findings in the gray-matter with structural DTI findings in the white-matter fiber tracts. The success of the proposed approach will not only greatly enhance our ability to diagnose mild TBI by detecting subtle neural injuries (e.g., loci and networks) that are invisible using conventional neuroimaging techniques, but also will provide the neuroimaging tools and software which can potentially be used as an objective evaluation method during pre- and post-intervention assessments of novel neuropharmacological and/or neuropsychological treatments for VA and active duty patients with TBI.