1Murdoch Children's Research Institute, Parkville.
2Melbourne School of Psychological Sciences, University of Melbourne.
J Neurosurg Pediatr. 2024 Jul 26;34(4):373-383. doi: 10.3171/2024.6.PEDS2499. Print 2024 Oct 1.
Posttraumatic headache (PTH) represents the most common acute and persistent postconcussive symptom (PCS) in children after concussion, yet there remains a lack of valid and objective biomarkers to facilitate risk stratification and early intervention in this patient population. Fixel-based analysis of diffusion-weighted imaging, which overcomes constraints of traditional diffusion tensor imaging analyses, can improve the sensitivity and specificity of detecting white matter changes postconcussion. The aim of this study was to investigate whole-brain and tract-based differences in white matter morphology, including fiber density (FD) and fiber bundle cross-section (FC) area in children with PCSs and PTH at 2 weeks after concussion.
This prospective longitudinal study recruited children aged 5-18 years who presented to the emergency department of a tertiary pediatric hospital with a concussion sustained within the previous 48 hours. Participants underwent diffusion-weighted MRI at 2 weeks postinjury. Whole-brain white matter statistical analysis was performed at the level of each individual fiber population within an image voxel (fixel) to compute FD, FC, and a combined metric (FD and bundle cross-section [FDC]) using connectivity-based fixel enhancement. Tract-based Bayesian analysis was performed to examine FD in 23 major white matter tracts.
Comparisons of 1) recovered (n = 27) and symptomatic (n = 16) children, and those with 2) PTH (n = 13) and non-PTH (n = 30; overall mean age 12.99 ± 2.70 years, 74% male) found no fiber-specific white matter microstructural differences in FD, FC, or FDC at 2 weeks postconcussion, when adjusting for age and sex (family-wise error rate corrected p value > 0.05). Tract-based Bayesian analysis showed evidence of no effect of PTH on FD in 10 major white matter tracts, and evidence of no effect of recovery group on FD in 3 white matter tracts (Bayes factor < 1/3).
Using whole-brain fixel-wise and tract-based analyses, these findings indicate that fiber-specific properties of white matter microstructure are not different between children with persisting PCSs compared with recovered children 2 weeks after concussion. These data extend the limited research on white matter fiber-specific morphology while overcoming limitations inherent to traditional diffusion models. Further validation of our findings with a large-scale cohort is warranted.
创伤后头痛（PTH）是儿童脑震荡后最常见的急性和持续性脑震荡后症状（PCS），但仍缺乏有效的客观生物标志物来对该患者人群进行风险分层和早期干预。基于固定点的弥散加权成像分析可以克服传统弥散张量成像分析的限制，提高检测脑震荡后白质变化的敏感性和特异性。本研究旨在探讨脑震荡后 2 周时伴有 PCS 和 PTH 的儿童全脑和基于束的白质形态差异，包括纤维密度（FD）和纤维束横截面积（FC）。
本前瞻性纵向研究招募了年龄在 5-18 岁之间的患儿，这些患儿在过去 48 小时内出现过脑震荡，并在三级儿科医院的急诊室就诊。参与者在损伤后 2 周进行弥散加权 MRI。通过基于连接的固定点增强，在图像体素（固定点）内对每个单独的纤维群体进行全脑白质统计分析，以计算 FD、FC 和联合度量（FD 和束横截面[FDC]）。采用基于束的贝叶斯分析方法，对 23 条主要白质束中的 FD 进行了分析。
对 1）康复（n = 27）和症状性（n = 16）患儿的比较，以及对 2）PTH（n = 13）和非 PTH（n = 30；平均年龄 12.99 ± 2.70 岁，74%为男性）的比较，在调整年龄和性别后，在脑震荡后 2 周时未发现 FD、FC 或 FDC 在纤维特异性白质微观结构上有差异（校正后的错误发现率 p 值>0.05）。基于束的贝叶斯分析表明，PTH 对 10 条主要白质束的 FD 没有影响，而康复组对 3 条白质束的 FD 没有影响（贝叶斯因子<1/3）。
使用全脑固定点和基于束的分析，这些发现表明，与脑震荡后康复的儿童相比，持续 PCS 儿童的白质微观结构纤维特异性性质没有差异。这些数据扩展了对白质纤维特异性形态的有限研究，同时克服了传统扩散模型固有的局限性。需要进一步用大规模队列验证我们的发现。
