MR elastography-based detection of impaired decoupling performance of the pia-arachnoid complex (PAC) associated with repetitive head impacts

项目总结/摘要 在接触性运动中持续的重复性头部撞击（RHI）是一个日益严重的公共健康问题。尽管RHI可能 使用常规成像技术不会引起可观察到的脑损伤，越来越多的证据表明，如果 持续重复的低水平亚震荡性头部撞击可导致严重的头部损伤， 震荡敏感性尽管如此，识别遭受RHI引起的损伤的个体仍然具有挑战性，因为它们是 通常无症状，当用当前诊断进行评估时。迫切需要开发新的评估工具， 这些工具可以检测到轻微但重复的影响的渐进性微妙变化，以确定RHI引起的损伤 无症状状态。虽然亚脑震荡，RHI可能是一个足够的创伤负荷，破坏大脑的保护， 膜系统（即，蛛网膜复合体（PAC），并逐渐降低其保护功能， 个人在未来很容易受到伤害。虽然目前的成像方式看不见，但我们的假设是PAC 功能状态可以通过评估由PAC调节的颅骨-脑（SB）解耦性能来检测， 和以前经历过RHI的个人相比， 没有RHI病史的正常志愿者，可能反映了RHI后PAC的降解。目前， 不存在量化SB去耦性能及其在RHI之后的潜在退化的非侵入性工具。 我们的目标是（1）开发和探索新的磁共振弹性成像（MRE）技术， 量化SB机械解耦性能和（2）建立新的定量生物标志物， RHI诱导的人类PAC损伤。在目标1中，我们将开发一种新的基于MRE的成像技术， 量化各种载荷条件下SB界面的动态力学耦合参数。这 新系统将集成多激励头驱动器系统，诱导所需的各种机械刺激 （包括振动频率/方向/预载的变化），脉冲序列估计相应的全容积 三维SB位移场，和后处理方法评估所得的SB耦合参数在体内。 这将为描述PAC的传输率、连接性、传输系数， 方向变化和负载敏感性，可能区分健康的PAC和PAC， 功能退化在目标2中，我们将评价MRE评估的SB偶联的重复性和再现性 参数在健康志愿者中使用测试-重测策略。还将进行一项初步临床研究， 并比较年龄/性别匹配的正常和RHI参与者中MRE评估的SB偶联参数。采取 总之，这些目标将为研究SB生物力学提供创新的方法和独特的数据集， 成像生物标志物，以帮助临床医生识别持续存在RHI诱导的PAC损伤的个体。 更广泛地说，该项目将扩大我们对RHI累积效应的理解，促进 识别可能需要监测以避免长期暴露于RHI的高风险个体。

PROJECT SUMMARY/ ABSTRACT Repetitive head impacts (RHI) sustained in contact sports is a growing public health issue. Even though RHI may not cause an observable brain injury with conventional imaging techniques, growing evidence indicates that if sustained repetitively, subconcussive low levels of head impact can cause significant head injury and increase the concussion susceptibility. Still, identification of individuals who sustain RHI-induced injury is challenging as they are often asymptomatic when evaluated with current diagnostics. An urgent need exists to develop new assessment tools that detect progressive subtle changes from minor, but repeated impacts to identify RHI-induced injury in its asymptomatic state. While subconcussive, RHI may be a sufficient trauma load to disrupt the brain’s protective membrane system (i.e., pia-arachnoid complex, or PAC) and progressively degrade its protective function, placing the individual vulnerable to future injury. Although invisible with current imaging modalities, our hypothesis is PAC functional status can be detected by assessing skull-brain (SB) decoupling performance modulated by the PAC, and individuals who have previously experienced RHI will have changes in SB decoupling performance compared with normal volunteers with no history of RHI, presumably reflecting the PAC degradation following RHI. Currently, a noninvasive tool to quantify SB decoupling performance and its potential degradation following RHI does not exist. Our goals are to (1) develop and explore novel magnetic resonance elastography (MRE)-based techniques for quantifying SB mechanical decoupling performance and (2) establish new quantitative biomarkers assessing the RHI-induced injury to the PAC in humans. In Aim 1, we will develop a new MRE-based imaging technique to quantify the dynamic mechanical coupling parameters of the SB interface under various loading conditions. This new system will integrate a multi-excitation head driver system inducing the desired various mechanical stimuli (including changes in vibration frequency/direction/preload), a pulse sequence estimating corresponding full-volume 3D SB displacement fields, and a post-processing approach assessing resultant SB coupling parameters in vivo. This will create a foundation to characterize the PAC’s transmissibility, connectivity, transmission coefficients, directional variation, and loading sensitivity, possibly distinguishing between a healthy PAC and a PAC with degraded function. In Aim 2, we will evaluate the repeatability and reproducibility of the MRE-assessed SB coupling parameters in healthy volunteers using a test-retest strategy. A pilot clinical study will also be performed to evaluate and compare MRE-assessed SB coupling parameters in age-/sex-matched normal and RHI participants. Taken together, these aims will provide innovative methods and unique datasets for studying SB biomechanics, and novel imaging biomarkers to aid clinicians in identifying individuals who have sustained the RHI-induced injury to the PAC. More broadly, this project will expand our understanding of the cumulative effects of RHI, facilitating the identification of high risk individuals who may require surveillance to avoid prolonged exposure to RHI.