Objective Translational Multi-domain Early Concussion Assessment

客观转化多领域早期脑震荡评估

• 批准号: 9310317
• 负责人: Kristy Arbogast
• 金额: $ 103.88万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9310317
• 关键词: Acute; Adolescent; Affect; Age; Animal Model; Animals; Attention; Awareness; Behavior; Behavioral; Benchmarking; Biological Markers; Biomechanics; Biomedical Engineering; Brain; Brain Concussion; Child; Childhood; Clinical; Cognitive; Computer Simulation; Country; Data; Diagnosis; Diagnostic; Emotional; Enrollment; Ensure; Equilibrium; Equipment; Equipment Design; Exposure to; Eye; Family suidae; Female; Field Hockey; Frequencies; Future; Gender; Goals; Golf; Head; Healthcare; High School Student; Human; Ice Hockey; Incidence; Injury; Institute of Medicine (U.S.); Knowledge; Lacrosse; Lead; Long-Term Effects; Longitudinal Studies; Manufactured Baseball; Manufactured basketball; Manufactured football; Measures; Memory; Methods; Modeling; Motion; Motor; Neurocognitive; Neurological outcome; Neurosciences; Outcome; Patients; Physical Education; Physiological Processes; Play; Prevention strategy; Preventive Intervention; Process; Protective Devices; Quality of life; Recovery; Reporting; Research; Research Design; Research Project Grants; Risk; Risk Factors; Role; Rotation; Sample Size; Seasons; Serum; Short-Term Memory; Sleep; Soccer; Softball; Specificity; Sports; Students; Symptoms; Technology; Teenagers; Tennis; Testing; Time; Translating; Traumatic Brain Injury; Youth; actigraphy; auditory processing; base; boys; clinical Diagnosis; cohort; concussive symptom; design; experience; functional disability; functional outcomes; girls; head impact; high risk; improved; injury prevention; innovation; insight; interdisciplinary approach; male; mild traumatic brain injury; neuroimaging; neuropathology; new technology; novel; novel strategies; oculomotor; pediatric traumatic brain injury; processing speed; prognostic; prognostic value; sensor; sex; symptomatology; tool; visual processing; willingness

SUMMARY In the US, there are more than four sports-related traumatic brain injuries every minute. Sports-related concussion (SRC) in youth has received heightened attention due to emerging evidence that SRCs can affect academics, behavior, and neurocognitive processes, such as working memory, concentration, processing speed, and eye and motor function. A recent Institute of Medicine report on SRCs in youth revealed how little is known about concussion in the young brain, and called for urgent attention to determine the incidence of SRCs in boys and girls by sport and demographic; research to identify unbiased, sensitive prognostic and diagnostic metrics/markers; longitudinal studies to determine outcomes; and to delineate age- and sex-related biomechanical determinants of injury risk. This innovative hypothesis-driven Bioengineering Research Grant will generate objective diagnostic tools for use in concussion (Aim 1), new technologies to translate human outcome metrics to animals to provide a human-like platform to develop and test injury treatments in the future (Aim 2), and new knowledge regarding high-risk sports settings for youth (Aim 3) that will drive safety equipment design. The most innovative feature of the study is the integration across Aims to use BOTH male and female high school students and piglets in a deliberately parallel study design to determine optimal SRC assessments and identify mechanistic relationships between sex, loading conditions, and SRC symptoms. The integration of human and animal studies which employ similar neuro-functional assessments leverages the strengths of each approach: human studies ensure the study of biofidelic physiologic processes, and animal studies allow application of specific loading conditions and outcomes not easily measured in living humans, such as neuropathology. Extensive pilot data establish feasibility and sample sizes in all Aims. In Aim 1 an unbiased numerical assessment suite for SRC will be developed and independently validated to establish ≥95% sensitivity, and determine if these metrics are predictive of days-to-clearance for sports. Because the Aim 1 objective metrics are nonverbal and effort-independent, they have been “translated” to animals and reveal human-like physical, cognitive, and sleep symptoms of SRC in animals after rapid controlled head rotations. In Aim 2, single head rotations and multiple sub-concussive rotations are computationally scaled from teens to an immature large animal model of mild TBI, to identify the effects of sex and load frequency, magnitude and direction on neuro-function, biomarkers and neuropathology. Aim 2 will identify biomechanical settings of greatest risk for the young brain. The biomechanical insights from pigs in Aim 2 are translated to teens in Aim 3, where head impact sensors are used to quantify biomechanical load exposure by sport and sex, and the relationships between load exposure and neuro-functional metrics. The proposed studies in animals and humans will have broad impact – by reducing the healthcare burden of SRC, enhancing accurate and objective diagnosis, and identifying gender-specific prevention and intervention strategies.

摘要 在美国，每分钟都有超过四起与运动有关的创伤性脑损伤。与体育相关的 年轻人的脑震荡(SRC)受到了高度关注，因为越来越多的证据表明，SRC可以影响 学术、行为和神经认知过程，如工作记忆、注意力、加工 速度、眼睛和运动功能。医学研究所最近一份关于青年SRCs的报告揭示了 已知年轻脑震荡，并呼吁紧急关注确定SRCS的发生率 按运动和人口统计对男孩和女孩的影响；研究以确定公正、敏感的预后和诊断 指标/标记；确定结果的纵向研究；并描述与年龄和性别有关的 损伤风险的生物力学决定因素。这项创新的假设驱动的生物工程研究补助金 将产生用于脑震荡的客观诊断工具(目标1)，这是一项将人类 为动物提供一个类似人类的平台，以开发和测试未来的伤害治疗方法 (目标2)，以及关于青少年高危运动环境的新知识(目标3)，将推动安全 设备设计。这项研究最具创新性的特点是将两者的目标整合在一起 并对女高中生和仔猪进行有意平行的研究设计，以确定最优的SRC 评估和确定性别、负荷状况和SRC症状之间的机械关系。这个 采用类似神经功能评估的人类和动物研究的整合利用了 每种方法的优点：人体研究确保研究生物逼真的生理过程，以及动物 研究允许应用特定的负荷条件和结果，这些条件和结果在活人身上不易测量， 比如神经病理学。广泛的试点数据确定了所有目标的可行性和样本量。在AIM 1和 将开发和独立验证SRC的无偏数字评估套件，以建立 ≥95%的敏感度，并确定这些指标是否可以预测体育运动的清除天数。因为 目标1客观指标是非语言的和独立于努力的，它们已经被“翻译”给动物和 快速控制头部后的动物SRC的生理、认知和睡眠症状 旋转。在目标2中，计算了单头旋转和多个亚震荡旋转 从青少年到轻度脑外伤的未成熟大型动物模型，以确定性别和负荷频率的影响， 神经功能、生物标志物和神经病理学的大小和方向。目标2将确定生物力学 对年轻的大脑来说风险最大的环境。在目标2中来自猪的生物力学见解被翻译成 在Aim 3中，青少年使用头部撞击传感器来量化运动和性别带来的生物力学负荷， 以及负荷暴露和神经功能指标之间的关系。拟议中的动物研究 人类将产生广泛的影响-通过减少SRC的医疗负担，提高准确性和 目的诊断，并确定针对性别的预防和干预策略。