Effects of blood-brain barrier disruption upon white matter connectivity subsequent to traumatic brain injury

摘要/总结 人血脑屏障（BBB）破坏后连接体重组的动力学研究 创伤性脑损伤（TBI）仍然知之甚少。在人脑的磁共振成像（MRI）中， 磁共振加权成像（SWI）已成为临床识别微小肿瘤的首选序列。 血管，这是BBB破坏的指标。部分原因是血管壁可能比 机械弹性比轴突膜，（微）血管的存在是密切相关的， 扩散张量成像（DTI）显示的创伤性轴索损伤（TAI）。直到今天，很少有研究 以系统细节量化（A）白色物质（WM）连接性如何受到BBB破坏和TAI的影响， 以及（B）SWI分辨的微区（推测位于受TAI强烈影响的区域）如何导致 连接体的结构和功能组织的变化。如果不了解这些 在整个大脑的规模（而不是严格的区域或脑叶水平）的现象，它可能是非常 评估其对患者长期健康的真正影响具有挑战性。这项研究的目标是 项目是（A）评估轻度TBI中（微）损伤的后遗症，并（B）量化短期和长期损伤， 出血性损伤和机械剪切对神经和神经心理功能的远期影响 在轻度TBI患者中。这项工作可能会提供新的见解，如何BBB中断和机械剪切 导致神经和认知功能障碍。我们建议使用新的定量方法， 神经影像分析，以回答有关BBB破坏和TAI在脑缺血中的作用的基本问题。 人类连接体的重组具体而言，我们试图（1）量化WM的纵向演变 通过存在SWI可分辨的 （2）解决（微）空间的存在之间的时空关系。 在人类连接体中发生的TAI相关的变化，这些变化发生在治疗后的前12个月内。 损伤，以及（3）量化（微）损伤相关的BBB破坏，TAI和WM之间的相互作用 萎缩调节前12个月内神经心理功能的恶化和/或恢复 在TBI之后提高对（微）出血发生率和功能性 后遗症可以使脑震荡和其他形式的创伤性损伤的真正严重程度得到评估， 前期反过来，这可以使临床医生获得有关潜在后果的新见解， SWI分辨的（微）神经和神经心理功能损害。

ABSTRACT/SUMMARY The dynamics of human connectome reorganization following blood-brain barrier (BBB) disruption during traumatic brain injury (TBI) remains poorly understood. In magnetic resonance imaging (MRI) of the human brain, susceptibility-weighted imaging (SWI) has become the sequence of choice for the clinical identification of micro- hemorrhages, which are indicators of BBB disruption. Partly because blood vessel walls may be more mechanically elastic than axonal membranes, the presence of (micro-) hemorrhages is strongly correlated with that of traumatic axonal injury (TAI) as revealed by diffusion tensor imaging (DTI). To this day, few studies have quantified in systematic detail (A) how white matter (WM) connectivity is affected by BBB disruption and by TAI, and (B) how SWI-resolved micro-hemorrhages (presumably located in regions strongly affected by TAI) lead to changes in the structural and functional organization of the connectome. Without understanding these phenomena at the scale of the entire brain (rather than on a strictly regional or lobar level) it may be very challenging to assess their true impact upon patients' long-term well-being. The goal of this proposed research project is to (A) assess the sequelae of (micro-) hemorrhages in mild TBI and to (B) quantify the short- and long- term effects of hemorrhagic lesions and mechanical shearing upon neurological and neuropsychological function in patients with mild TBI. This work may provide novel insights into how BBB disruption and mechanical shearing of axons during TAI lead to neural and cognitive dysfunction. We propose to use novel quantitative methods for neuroimage analysis to answer fundamental questions pertaining to the role of BBB disruption and TAI in the reorganization of the human connectome. Specifically, we seek to (1) quantify the longitudinal evolution of WM connectivity in (peri-) lesional regions affected by BBB disruption as reflected by the presence of SWI-resolvable (micro-) hemorrhages, (2) resolve the spatio-temporal relationship between the presence of (micro-) hemorrhages, and TAI-related changes in the human connectome which occur within the first 12 months post- injury, and (3) quantify how the interplay between (micro-) hemorrhage-related BBB disruption, TAI and WM atrophy modulates the deterioration and/or recovery of neuropsychological function within the first 12 months after TBI. Improved understanding of these correlations between (micro-) bleed occurrence and functional sequelae could allow the true severity of concussions and other forms of traumatic injuries to be assessed at an early stage. In turn, this could allow clinicians to gain novel insights pertaining to the potential consequences of SWI-resolved (micro-) hemorrhages upon neurological and neuropsychological function.