Novel Neuroimaging and Neuropsychological Methods Sensitive to Cerebral Disruption in Veterans with Mild Traumatic Brain Injury

对轻度创伤性脑损伤退伍军人的脑损伤敏感的新型神经影像学和神经心理学方法

• 批准号: 10248786
• 负责人: Scott Francis Sorg
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-10-01 至 2025-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10248786
• 关键词: Acute; Address; Affect; Anisotropy; Area; Attenuated; Axon; Biological Markers; Brain; Brain region; Caring; Cerebrum; Characteristics; Cognitive; Complex; Conflict (Psychology); Conscious; Control Groups; Data; Detection; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Distal; Equilibrium; Evaluation; Fiber; Foundations; Future; Glean; Goals; Heterogeneity; Image; Individual; Individuation; Injury; Investigation; Joints; Literature; Magnetic Resonance Imaging; Measures; Methods; Nervous System Trauma; Neurobiology; Neurocognitive; Neuropsychological Tests; Neuropsychology; Outcome; Participant; Patients; Performance; Physiologic pulse; Post-Traumatic Stress Disorders; Probability; Property; Protocols documentation; Quality of life; Recording of previous events; Reporting; Research; Sampling; Scanning; Site; Symptoms; Techniques; Time; Tissues; Unconscious State; Veterans; Work; base; brain behavior; clinical decision-making; cognitive performance; comparison group; density; frontal lobe; functional outcomes; gray matter; imaging approach; imaging modality; improved; individual variation; mild traumatic brain injury; multidisciplinary; neuroimaging; neuroimaging marker; novel; psychiatric symptom; relating to nervous system; research clinical testing; simulation; tool; treatment response; white matter; white matter damage

Identification of neuroimaging-based markers sensitive to mild neurotrauma and neuropsychological markers of cognitive disruption is vital toward addressing the complex treatment needs of the large number of Veterans with histories of mTBI. Although neuroimaging methods, particularly in the area of diffusion imaging (dMRI) continue to show promise, there are significant limitations in the traditional, diffusion tensor imaging (DTI) based approach in white matter (WM), where a high degree of heterogeneity of WM axon orientations and sampling from disparate tissue types within a voxel contribute to inaccurate estimates of tissue properties. These limitations, inherent in standard and widely used DTI methods, likely attenuate DTI sensitivity in the detection of mild forms of neurotrauma, particularly in key, complex WM regions shown to be most susceptible to mTBI. Likewise, cognitive research findings have been mixed, with conflicting reports and unclear cognitive outcomes that likely cloud and confuse clinical decision-making. The heterogeneity of TBI, differences in injury characteristics, and a non-uniform cognitive profile among affected Veterans likely contribute to the decreased sensitivity and inconsistency shown across available studies that have typically leveraged traditional means-based comparisons of neuropsychological test scores. Indeed, indicators of mTBI often fail to align with imaging findings, as well the cognitive and functional outcomes reported by Veterans with histories of mTBI. In the proposed study, we seek to apply new tools and methods in order to more sensitively examine WM disruption and neuropsychological performance in 60 Veterans with mTBI and 60 Veterans without a history of TBI. Participants will complete a broad neurocognitive assessment and will undergo an dMRI scan. We propose that leveraging a novel neuroimaging approach—one that is robust to the limitations inherent in standard DTI protocols—will enable investigation of WM proximal to the sulcal depths where all-cause mTBI is thought to inflict the greatest damage given shearing effects in the gray-white matter border zone. We will use dMRI acquisition and analysis methods which combine single and double pulsed field gradient dMRI acquisitions via a novel technique called Joint Estimation Diffusion Imaging (JEDI) to integrate diffusion information at the voxel and subvoxel level. Equilibrium probability (EP), an anisotropy measure that is more robust to the complexities of crossing fibers and partial voluming effects, will be calculated using JEDI. In particular, we will interrogate EP of voxels residing within the border between the gray and WM within frontal the sulcal depths. Simulation and histopathological studies show these regions to be most susceptible to acute and distal effects of mild neurotrauma given shearing effects that are particularly damaging because of differing tissue densities of the gray-white border. Second, given our recent work showing the sensitivity of newer cognitive methods to detect neuropsychological deficits in mTBI, we will investigate intra-individuation cognitive performance variability (IIV) as a marker of cognitive disruption in order to enhance brain-behavior associations in Veterans compared to traditional comparison of group means. Taken together, the proposed study presents an opportunity to investigate white matter disruption within brain regions vulnerable to mTBI using a novel neuroimaging approach (JEDI), further assess a promising cognitive concept (IIV) which may improve the evaluation of clinical outcomes following mTBI, and examine potential associations between IIV and WM disruption in Veterans with mTBI. Such cutting-edge work can lay the foundation for enhanced understanding of the neurobiological underpinnings of mTBI and persisting postconcussive symptoms in Veterans with neurotrauma and may identify neuroimaging biomarkers useful to evaluate treatment response in future trials.

对轻度神经创伤敏感的神经影像学标记物和神经心理学标记物的鉴定 认知中断对于解决大量退伍军人的复杂治疗需求至关重要， mTBI的历史尽管神经成像方法，特别是在扩散成像（dMRI）领域， 为了显示前景，传统的基于弥散张量成像（DTI）的方法存在显著的局限性 在白色物质（WM）中，WM轴突方向和取样的高度异质性 体素内不同的组织类型导致组织特性的不准确估计。这些限制， 在标准和广泛使用的DTI方法中固有的，可能会减弱DTI在检测轻度形式中的灵敏度 神经创伤，特别是在关键的，复杂的WM区域被证明是最容易受到mTBI。同样地， 认知研究的结果喜忧参半，相互矛盾的报告和不明确的认知结果可能 影响和混淆临床决策。TBI的异质性，损伤特征的差异， 受影响的退伍军人中的不一致认知特征可能导致敏感性降低， 现有研究中显示的不一致性，这些研究通常利用传统的基于手段的 神经心理学测试分数的比较。事实上，mTBI的指标往往不能与成像结果一致， 以及有mTBI病史的退伍军人报告的认知和功能结果。 在这项研究中，我们寻求应用新的工具和方法，以更敏感地检查工作记忆 60名mTBI退伍军人和60名无mTBI病史的退伍军人的中断和神经心理学表现 创伤性脑损伤参与者将完成广泛的神经认知评估，并将接受dMRI扫描。我们提出 利用一种新的神经成像方法-一种对标准DTI固有局限性具有鲁棒性的方法， 协议-将能够调查近端脑沟深度的WM，其中认为全因mTBI会造成 在灰白质交界区的剪切效应中，损伤最大。我们将使用dMRI采集 和分析方法，其通过新颖的方法将单脉冲场梯度dMRI采集和双脉冲场梯度dMRI采集相结合， - 称为联合估计扩散成像（JEDI）的技术，以在体素处整合扩散信息， 亚体素水平。平衡概率（EP），一种各向异性度量，对以下复杂性更鲁棒： 交叉纤维和部分体积效应，将使用JEDI计算。特别是，我们将审问EP 位于脑沟深度前部内的灰色和WM之间的边界内的体素。仿真和 组织病理学研究表明，这些区域最容易受到轻度脑缺血的急性和远端影响， 由于不同的组织密度， 灰白色边框。第二，鉴于我们最近的工作显示了新的认知方法对检测的敏感性， 神经心理学缺陷的mTBI，我们将调查内个性化认知表现变异性（IIV） 作为认知中断的标志，以增强退伍军人的大脑行为关联， 传统的群体比较方法。总之，拟议的研究提供了一个机会， 使用一种新神经影像学方法研究易受mTBI影响的脑区内的白色破坏 （JEDI），进一步评估可能改善临床结局评价的有前景的认知概念（IIV） 在mTBI之后，并检查患有mTBI的退伍军人中IIV和WM中断之间的潜在关联。等 尖端的工作可以为增强对神经生物学基础的理解奠定基础， 神经创伤退伍军人的mTBI和持续性脑震荡后症状，可识别神经影像学 生物标志物可用于在未来的试验中评估治疗反应。