BACKGROUND It is well documented that infants born very preterm (VP) are at risk of brain injury and altered brain development in the neonatal period, however there is a lack of long-term, longitudinal studies on the effects of VP birth on white matter development over childhood. Most previous studies were based on voxel-averaged, non-fibre-specific diffusion magnetic resonance imaging (MRI) measures, such as fractional anisotropy. In contrast, the novel diffusion MRI analysis framework, fixel-based analysis (FBA), enables whole-brain analysis of microstructural and macrostructural properties of individual fibre populations at a sub-voxel level. We applied FBA to investigate the long-term implications of VP birth and associated perinatal risk factors on fibre development in childhood and adolescence. METHODS Diffusion images were acquired for a cohort of VP (born <30 weeks' gestation) and full-term (FT, ≥37 weeks' gestation) children at two timepoints: mean (SD) 7.6 (0.2) years (n=138 VP and 32 FT children) and 13.3 (0.4) years (n=130 VP and 45 FT children). 103 VP and 21 FT children had images at both ages for longitudinal analysis. At every fixel (individual fibre population within an image voxel) across the white matter, we compared FBA metrics (fibre density (FD), cross-section (FC) and a combination of these properties (FDC)) between VP and FT groups cross-sectionally at each timepoint, and longitudinally between timepoints. We also examined associations between known perinatal risk factors and FBA metrics in the VP group. RESULTS Compared with FT children, VP children had lower FD, FC and FDC throughout the white matter, particularly in the corpus callosum, tapetum, inferior fronto-occipital fasciculus, fornix and cingulum at ages 7 and 13 years, as well as the corticospinal tract and anterior limb of the internal capsule at age 13 years. VP children also had slower FDC development in the corpus callosum and corticospinal tract between ages 7 and 13 years compared with FT children. Within VP children, earlier gestational age at birth, lower birth weight z-score, and neonatal brain abnormalities were associated with lower FD, FC and FDC throughout the white matter at both ages. CONCLUSIONS VP birth and concomitant perinatal risk factors are associated with fibre tract-specific alterations to axonal development in childhood and adolescence.

中文翻译：

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早产后长达 13 年的白质纤维密度和形态的长期发展：基于固定素的分析

背景 有充分证据表明，极早产 (VP) 婴儿在新生儿期有脑损伤和大脑发育改变的风险，但缺乏关于 VP 出生对白质发育影响的长期纵向研究在童年。以前的大多数研究都是基于体素平均、非纤维特异性扩散磁共振成像 (MRI) 测量，例如分数各向异性。相比之下，新的扩散 MRI 分析框架，即基于固定素的分析 (FBA)，可以在亚体素水平上对单个纤维群的微观结构和宏观结构特性进行全脑分析。我们应用 FBA 来研究 VP 出生和相关围产期危险因素对儿童和青春期纤维发育的长期影响。方法 在两个时间点获取一组 VP（出生 <30 周）和足月（FT，妊娠 37 周以上）儿童的扩散图像：平均 (SD) 7.6 (0.2) 年 (n=138 VP)和 32 名 FT 儿童）和 13.3 (0.4) 岁（n=130 VP 和 45 名 FT 儿童）。103 名 VP 和 21 名 FT 儿童都有两个年龄段的图像用于纵向分析。在整个白质的每个固定素（图像体素内的单个纤维群）上，我们比较了 VP 和 FT 组之间的 FBA 指标（纤维密度 (FD)、横截面 (FC) 和这些属性的组合 (FDC)）。 -在每个时间点分段，以及在时间点之间纵向。我们还检查了 VP 组中已知的围产期风险因素与 FBA 指标之间的关联。结果 与 FT 儿童相比，VP 儿童整个白质的 FD、FC 和 FDC 较低，特别是在 7 岁和 13 岁的胼胝体、绒毡层、下额枕束、穹窿和扣带，以及 13 岁的皮质​​脊髓束和内囊前肢。与 FT 儿童相比，VP 儿童在 7 至 13 岁之间胼胝体和皮质脊髓束的 FDC 发育也较慢。在 VP 儿童中，较早的出生胎龄、较低的出生体重 z 分数和新生儿脑部异常与两个年龄段的整个白质的 FD、FC 和 FDC 较低有关。结论 VP 出生和伴随的围产期危险因素与儿童和青春期轴突发育的纤维束特异性改变有关。以及 13 岁时的皮质脊髓束和内囊前肢。与 FT 儿童相比，VP 儿童在 7 至 13 岁之间胼胝体和皮质脊髓束的 FDC 发育也较慢。在 VP 儿童中，较早的出生胎龄、较低的出生体重 z 分数和新生儿脑部异常与两个年龄段的整个白质的 FD、FC 和 FDC 较低有关。结论 VP 出生和伴随的围产期危险因素与儿童和青春期轴突发育的纤维束特异性改变有关。以及 13 岁时的皮质脊髓束和内囊前肢。与 FT 儿童相比，VP 儿童在 7 至 13 岁之间胼胝体和皮质脊髓束的 FDC 发育也较慢。在 VP 儿童中，较早的出生胎龄、较低的出生体重 z 分数和新生儿脑部异常与两个年龄段的整个白质的 FD、FC 和 FDC 较低有关。结论 VP 出生和伴随的围产期危险因素与儿童和青春期轴突发育的纤维束特异性改变有关。出生时较早的胎龄、较低的出生体重 z 分数和新生儿脑部异常与两个年龄的整个白质的 FD、FC 和 FDC 较低有关。结论 VP 出生和伴随的围产期危险因素与儿童和青春期轴突发育的纤维束特异性改变有关。出生时较早的胎龄、较低的出生体重 z 分数和新生儿脑部异常与两个年龄的整个白质的 FD、FC 和 FDC 较低有关。结论 VP 出生和伴随的围产期危险因素与儿童和青春期轴突发育的纤维束特异性改变有关。