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: 10426236
• 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 2022-10-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10426236
• 关键词: Acute; Address; Affect; Anisotropy; Area; Attenuated; Axon; Biological Markers; Brain; Brain region; Caring; Cerebrum; Characteristics; Cognitive; Complex; Confusion; Conscious; Control Groups; Data; Detection; Diffusion; Diffusion Magnetic Resonance Imaging; Disparate; 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-Concussion Syndrome; Post-Traumatic Stress Disorders; Predisposition; Probability; Property; Protocols documentation; Quality of life; Recording of previous events; Reporting; Research; Sampling; Scanning; Site; Techniques; Time; Tissues; Unconscious State; Veterans; Work; brain behavior; clinical decision-making; cognitive performance; comparison control; comparison group; frontal lobe; functional outcomes; gray matter; imaging approach; imaging modality; improved; individual variation; mild traumatic brain injury; multidisciplinary; neural; neuroimaging; neuroimaging marker; novel; psychiatric symptom; 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.

鉴定对轻度神经创伤敏感的基于神经影像的标记物和神经心理学标记物 cognitive disruption is vital toward addressing the complex treatment needs of the large number of Veterans with mTBI 病史。 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 在白质 (WM) 中，WM 轴突方向和采样具有高度异质性 disparate tissue types within a voxel contribute to inaccurate estimates of tissue properties.这些限制， 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.同样地， cognitive research findings have been mixed, with conflicting reports and unclear cognitive outcomes that likely 使临床决策变得模糊和混乱。 The heterogeneity of TBI, differences in injury characteristics, and a 受影响的退伍军人的认知状况不一致可能导致敏感性下降和 inconsistency shown across available studies that have typically leveraged traditional means-based 神经心理学测试分数的比较。 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 60 名患有 mTBI 的退伍军人和 60 名没有 mTBI 病史的退伍军人的破坏和神经心理学表现 创伤性脑损伤。 Participants will complete a broad neurocognitive assessment and will undergo an dMRI scan.我们建议 利用一种新颖的神经影像方法，该方法能够克服标准 DTI 固有的局限性 协议——将能够调查接近脑沟深度的 WM，认为全因 mTBI 会造成该深度 the greatest damage given shearing effects in the gray-white matter border zone.我们将使用 dMRI 采集 and analysis methods which combine single and double pulsed field gradient dMRI acquisitions via a novel 称为联合估计扩散成像 (JEDI) 的技术可整合体素处的扩散信息和 亚体素水平。 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.特别是，我们将询问 EP 体素位于额沟深度内的灰色和 WM 之间的边界内。模拟和 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 灰白色边框。 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) 作为认知破坏的标志，以增强退伍军人的大脑行为关联 传统的组均值比较。 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），进一步评估一个有前途的认知概念（IIV），这可能会改善临床结果的评估 继 mTBI 后，并检查患有 mTBI 的退伍军人中 IIV 和 WM 破坏之间的潜在关联。这样的 cutting-edge work can lay the foundation for enhanced understanding of the neurobiological underpinnings of 患有神经外伤的退伍军人中的 mTBI 和持续性脑震荡后症状可能会通过神经影像学来识别 生物标志物可用于评估未来试验中的治疗反应。