The underlying pathophysiology of paediatric mild traumatic brain injury and the time-course for biological recovery remains widely debated, with clinical care principally informed by subjective self-report. Similarly, clinical evidence indicate that adolescence is a risk factor for prolonged recovery, but the impact of age-at-injury on biomarkers has not been determined in large, homogeneous samples. The current study collected diffusion magnetic resonance imaging data in consecutively recruited patients (N = 203; 8-18 years old) and age and sex-matched healthy controls (N = 170) in a prospective cohort design. Patients were evaluated sub-acutely (1-11 days post-injury) as well as at four months post-injury (early-chronic phase). Healthy participants were evaluated at similar times to control for neurodevelopment and practice effects. Clinical findings indicated persistent symptoms at four months for a significant minority of patients (22%), along with residual executive dysfunction and verbal memory deficits. Results indicated increased fractional anisotropy and reduced mean diffusivity for patients, with abnormalities persisting up to four months post-injury. Multicompartmental geometric models indicated that estimates of intracellular volume fractions were increased in patients, whereas estimates of free water fractions were decreased. Critically, unique areas of white matter pathology (increased free water fractions or increased neurite dispersion) were observed when standard assumptions regarding parallel diffusivity were altered in multicompartmental models to be more biologically plausible. Cross-validation analyses indicated that some diffusion findings were more reproducible when approximately 70% of the total sample (142 patients, 119 controls) were used in analyses, highlighting the need for large-sample sizes to detect abnormalities. Supervised machine learning approaches (random forests) indicated that diffusion abnormalities increased overall diagnostic accuracy (patients vs. controls) by approximately 10% after controlling for current clinical gold standards, with each diffusion metric accounting for only a few unique percentage points. In summary, current results suggest that novel multicompartmental models are more sensitive to paediatric mild traumatic brain injury pathology, and that this sensitivity is increased when using parameters that more accurately reflect diffusion in healthy tissue. Results also suggest that diffusion data may be insufficient to achieve a high degree of objective diagnostic accuracy in patients when used in isolation, which is to be expected given known heterogeneities in pathophysiology, mechanism of injury, and even criteria for diagnoses. Finally, current results suggest ongoing clinical and physiological recovery at four months post-injury.

中文翻译：

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小儿轻度创伤性脑损伤的多室模型和弥散异常

儿科轻度创伤性脑损伤的基本病理生理学和生物恢复的时间进程仍然存在广泛争议，临床护理主要通过主观自我报告来了解。同样，临床证据表明，青春期是长期恢复的危险因素，但受伤年龄对生物标志物的影响尚未在大量同质样本中确定。目前的研究在前瞻性队列设计中收集了连续招募的患者（N = 203；8-18 岁）以及年龄和性别匹配的健康对照（N = 170）的扩散磁共振成像数据。对患者进行亚急性期（受伤后 1-11 天）以及受伤后四个月（慢性早期）的评估。在相似的时间对健康参与者进行评估，以控制神经发育和练习效果。临床结果表明，极少数患者（22%）在四个月时出现持续症状，并伴有残余的执行功能障碍和言语记忆缺陷。结果表明，患者各向异性分数增加，平均扩散率降低，异常现象持续长达四个月后。多室几何模型表明，患者的细胞内体积分数的估计值增加，而自由水分数的估计值减少。至关重要的是，当在多室模型中改变有关平行扩散率的标准假设以使其在生物学上更加合理时，观察到白质病理学的独特区域（增加的自由水分数或增加的神经突分散）。交叉验证分析表明，当大约 70% 的总样本（142 名患者，119 名对照）用于分析时，一些扩散结果的可重复性更高，这凸显了需要大样本量来检测异常。监督机器学习方法（随机森林）表明，在控制当前的临床金标准后，扩散异常将整体诊断准确性（患者与对照）提高了约 10%，而每个扩散指标仅占几个独特的百分点。总之，目前的结果表明，新型多室模型对儿科轻度创伤性脑损伤病理学更敏感，并且当使用更准确地反映健康组织中扩散的参数时，这种敏感性会增加。结果还表明，单独使用时，扩散数据可能不足以在患者​​中实现高度客观的诊断准确性，考虑到病理生理学、损伤机制甚至诊断标准的已知异质性，这是可以预料的。最后，目前的结果表明在受伤后四个月内正在进行临床和生理恢复。