Linking Injury Severity to Brainstem White Matter Integrity: A Tractography Study

将损伤严重程度与脑干白质完整性联系起来：纤维束成像研究

• 批准号: 8634881
• 负责人: Lisa Marie Delano-Wood
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8634881
• 关键词: Acceleration; Address; Amnesia; Anatomy; Animals; Anisotropy; Anxiety; Area; Attention; Awareness; Biological Markers; Blast Cell; Blast Injuries; Brain; Brain Stem; Brain region; Cardiovascular system; Case Mixes; Characteristics; Chronic; Chronic Phase; Clinical; Clinical Research; Cognition; Cognitive; Coma; Corticospinal Tracts; Coupled; Craniocerebral Trauma; Data; Deceleration; Diagnosis; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Dizziness; Equilibrium; Evaluation; Exhibits; Frequencies; Functional disorder; Human; Image; Imaging Techniques; Inferior; Injury; Knowledge; Link; Maintenance; Measurement; Medial; Medial lemniscus; Mental Depression; Methodology; Methods; Metric; Military Personnel; Motor; Myelin; Nausea; Outcome; Participant; Pathologic Processes; Pathology; Patients; Pontine structure; Population; Post-Concussion Syndrome; Post-Traumatic Stress Disorders; Posture; Proxy; Radial; Recording of previous events; Reporting; Research; Resolution; Respiratory physiology; Secondary to; Sensory; Severities; Sleep; Sleep disturbances; Sleeplessness; Slice; Structure; Subgroup; Symptoms; Syndrome; TBI Patients; Techniques; Tegmentum Mesencephali; Time; Tinnitus; Tissues; Traumatic Brain Injury; Unconscious State; Veterans; Vulnerable Populations; alertness; combat; executive function; experience; indexing; interest; multidisciplinary; negative mood; neurobehavioral; neuroimaging; neuropathology; neuropsychiatry; novel; psychosocial; public health relevance; sleep regulation; white matter; white matter change; white matter injury

Although the vast majority of all head injuries are classified as mild to moderate, many patients report persistent neuropsychiatric symptoms, despite normal clinical neuroimaging. Generally, traumatic brain injury (TBI) is difficult to detect and diagnose, and the scope of the problem is compounded significantly given that we know very little about the neuropathology and sequelae of neurotrauma. Historically, the brainstem has been implicated as a particularly vulnerable structure in the context of TBI. However, unfortunately, to our knowledge, there are no existing data relating injury severity variables (e.g., loss of consciousness [LOC]~ post-traumatic amnesia [PTA]~ number and frequency of blasts) as well as commonly experienced post-concussive symptoms (PCS~ e.g., sleep difficulties, balance/coordination problems, dizziness, tinnitus) to actual pathology in the human brain, and this could be directly related to the inability to visualize small, critical white matter tracts within the brainstem, a vital structure that is critically important for respiratory function, cardiovascular regulation, and sleep and alertness. Although it is thought that diffusion tensor imaging (DTI) can help address the shortcomings of conventional imaging techniques in the evaluation of patients with TBI, there is a lack of comprehensive, multidisciplinary TBI studies focusing on brainstem white matter integrity and injury severity markers, and research examining this population has been extremely limited. For example, to date, whole-brain DTI data in humans have been collected using multislice acquisition techniques that have limited imaging resolution to perform measurements with very thin slices, prohibiting the study of small white matter tracts and deep intracranial structures (i.e., brainstem). Indeed, there are very few brainstem DTI studies in TBI, and none have assessed associations to important injury severity variables and enduring neuropsychiatric symptoms comprising the posttraumatic syndrome. Despite a paucity of DTI studies in TBI, promising findings from animal and clinical studies-as well as our own pilot data in support of this proposal-provide preliminary support for the potential use of DTI as a biomarker of TBI-related white matter injury. We thus propose to use a newly developed methodology (HARDI~ described in the Methods section of the proposal) coupled with high spatial-resolution anatomic images in order to help identify and visualize important brainstem tracts that may represent the anatomical substrates of TBI. Using this approach, millimetric slices and probabilistic tractography allow thinner brainstem tracts to be identified, especially within low anisotropic areas. Thus, in 190 veterans and combat controls (mild to moderate TBI: 120~ combat and non-combat exposed NC: 70), we will employ DTI tractography in the context of a novel, cutting edge imaging sequence and analytic approach in order to fully segment and properly visualize critical brainstem white matter tracts and relate white matter integrity to important injury severity variables and PCS symptoms across mechanism of injury (blast versus blunt force TBI). Primary aims will also examine whether and how other important injury variables (e.g., number and proximity of blasts) modify the relationship between white matter integrity and PCS symptoms in this vulnerable population. To our knowledge, our proposal represents the first to fully segment and properly visualize critical brainstem white matter tracts, examine brainstem white matter integrity by mechanism of neurotrauma, and relate DTI indices to important injury severity and PCS variables. We expect that findings will advance our knowledge of the clinical utility of DTI in identifying specific brainstem white matter changes in mild to moderate TBI, and they will provide novel information about the effects of differing mechanisms of injury on brain regions that have been shown in tissue studies to be particularly vulnerable to the effects of TBI. Clearly, linkages of injury severity characteristics and enduring PCS symptoms typically associated with vegetative signs of psychiatric origin to a neuroanatomic substrate would have very important implications for this relatively new field.

虽然绝大多数的头部损伤被归类为轻度至中度，但许多患者报告说， 持续的神经精神症状，尽管正常的临床神经影像学。一般来说，创伤性脑损伤 (TBI)很难检测和诊断，而且问题的范围大大复杂化，因为我们 对神经病理学和神经创伤后遗症知之甚少。从历史上看， 在TBI的背景下，它被认为是一个特别脆弱的结构。然而不幸的是据我们所知 没有关于损伤严重性变量的现有数据（例如，意识丧失[编辑] 健忘症[PTA]-原始细胞的数量和频率）以及常见的脑震荡后 症状（PCS-例如，睡眠困难、平衡/协调问题、头晕、耳鸣）到实际病理学 这可能与无法看到小的、关键的白色物质束直接相关 脑干是一个重要的结构，对呼吸功能、心血管功能和心脏功能至关重要。 调节、睡眠和警觉性。尽管人们认为弥散张量成像（DTI）可以帮助解决 传统的成像技术在评价TBI患者中的缺点，缺乏 关注脑干白色物质完整性和损伤严重程度的全面、多学科TBI研究 标记物，研究这一人群的研究非常有限。例如，到目前为止，全脑 在人类的DTI数据已收集使用多层采集技术，具有有限的成像 分辨率进行测量非常薄的切片，禁止研究小白色物质束， 深部颅内结构（即，脑干）。事实上，在TBI中很少有脑干DTI研究， 已经评估了与重要损伤严重程度变量和持久神经精神症状的关联 包括创伤后综合症。 尽管针对TBI的DTI研究很少，但动物和临床研究以及 我们自己的试验数据支持这一提议-提供初步支持的潜在使用DTI作为一个 TBI相关白色损伤的生物标志物。因此，我们建议使用新开发的方法（HARDI~ 在提案的方法部分中描述）结合高空间分辨率解剖图像， 以帮助识别和可视化可能代表TBI解剖基质的重要脑干束。 使用这种方法，毫米级切片和概率纤维束成像允许更薄的脑干束， 特别是在低各向异性区域内。因此，在190名退伍军人和战斗控制（轻度至中度 TBI：120~战斗和非战斗暴露NC：70），我们将在小说的背景下采用DTI纤维束成像， 最先进的成像序列和分析方法，以充分分割和适当可视化关键 脑干白色物质束，并将白色物质完整性与重要的损伤严重程度变量和PCS相关 损伤机制中的症状（冲击波与钝力TBI）。主要目标还将审查是否 以及其他重要的损伤变量（例如，爆炸的数量和接近度）改变了 白色物质完整性和PCS症状在这个脆弱的人群。据我们所知，我们的建议 代表了第一个完全分割和正确可视化关键脑干白色物质束的人，检查 脑干白色物质完整性与神经损伤机制关系及DTI指标与重要损伤的关系 严重度和PCS变量。 我们预计这些发现将促进我们对DTI临床实用性的了解， 在轻度至中度TBI中识别特定的脑干白色物质变化，并且它们将提供新的 关于不同损伤机制对脑区域的影响的信息， 研究特别容易受到TBI的影响。显然，损伤严重程度特征和 持久的PCS症状通常与神经解剖学上的精神起源的植物性体征相关， 衬底将对这个相对较新的领域产生非常重要的影响。