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

项目摘要/摘要 接触性运动中的重复头部撞击(RHI)是一个日益严重的公共卫生问题。即使RHI可能 用传统的成像技术不会造成明显的脑损伤，越来越多的证据表明，如果 持续的、亚震荡的低水平头部撞击会导致严重的头部损伤，并增加 脑震荡易感性。尽管如此，识别遭受RHI损伤的个人仍然是具有挑战性的 当用目前的诊断进行评估时，通常没有症状。迫切需要制定新的评估方法 检测微小但重复影响的渐进性细微变化的工具，以识别RHI在其 无症状状态。虽然是亚震荡，但RHI可能是足够的创伤负荷，扰乱了大脑的保护性 膜系统(即软脑膜-蛛网膜复合体，或PAC)并逐渐降低其保护功能，放置 易受未来伤害的个体。尽管目前的成像方式不可见，但我们的假设是PAC 可以通过评估由PAC调制的颅脑(SB)去耦合性能来检测功能状态， 与之前经历过RHI的个体相比，SB脱钩性能会有变化 没有RHI病史的正常志愿者，可能反映了RHI后PAC的降解。目前， 没有一种非侵入性的工具来量化SB去耦合性能及其在RHI之后的潜在退化。 我们的目标是(1)开发和探索基于磁共振弹性成像(MRE)的新技术 量化Sb的机械脱钩性能；(2)建立新的定量生物标志物 RHI对人PAC的损伤作用。在目标1中，我们将开发一种新的基于MRE的成像技术来 量化了不同加载条件下Sb界面的动态力学耦合参数。这 新系统将集成多激励磁头驱动系统，以产生所需的各种机械刺激 (包括振动频率/方向/预载的变化)，估计对应的满量的脉冲序列 三维Sb位移场，以及一种在活体内评估结果Sb耦合参数的后处理方法。 这将为表征PAC的传递性、连通性、传输系数、 方向性变化和负载敏感性，可能区分健康的PAC和有 功能退化。在目标2中，我们将评估经MRE评估的SB耦合的重复性和再现性 采用重测策略对健康志愿者进行参数测试。还将进行一项初步的临床研究，以评估 并比较年龄/性别匹配的正常受试者和RHI受试者的MRE评估的SB耦合参数。已被占用 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，并具有新颖性 成像生物标志物，以帮助临床医生识别遭受RHI诱导的PAC损伤的个人。 更广泛地说，这个项目将扩大我们对RHI累积影响的理解，促进 识别可能需要监测以避免长期暴露于RHI的高危个人。

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.