Neurosciences and Mental Health, The Hospital for Sick Children Research Institute, Toronto, ON, Canada; Department of Paediatrics, The Hospital for Sick Children and the University of Toronto, Toronto, ON, Canada.
Department of Pediatric Cardiology, Benioff Children's Hospital and University of California, San Francisco, CA, USA.
Neuroimage. 2019 Jan 15;185:742-749. doi: 10.1016/j.neuroimage.2018.06.004. Epub 2018 Jun 15.
Neonates with congenital heart disease (CHD) are at high risk of punctate white matter injury (WMI) and impaired brain development. We hypothesized that WMI in CHD neonates occurs in a characteristic distribution that shares topology with preterm WMI and that lower birth gestational age (GA) is associated with larger WMI volume.
(1) To quantitatively assess the volume and location of WMI in CHD neonates across three centres. (2) To compare the volume and spatial distribution of WMI between term CHD neonates and preterm neonates using lesion mapping.
In 216 term born CHD neonates from three prospective cohorts (mean birth GA: 39 weeks), WMI was identified in 86 neonates (UBC: 29; UCSF: 43; UCZ: 14) on pre- and/or post-operative T1 weighted MRI. WMI was manually segmented and volumes were calculated. A standard brain template was generated. Probabilistic WMI maps (total, pre- and post-operative) were developed in this common space. Using these maps, WMI in the term CHD neonates was compared with that in preterm neonates: 58 at early-in-life (mean postmenstrual age at scan 32.2 weeks); 41 at term-equivalent age (mean postmenstrual age at scan 40.1 weeks).
The total WMI volumes of CHD neonates across centres did not differ (p = 0.068): UBC (median = 84.6 mm, IQR = 26-174.7 mm); UCSF (median = 104 mm, IQR = 44-243 mm); UCZ (median = 121 mm, IQR = 68-200.8 mm). The spatial distribution of WMI in CHD neonates showed strong concordance across centres with predilection for anterior and posterior rather than central lesions. Predominance of anterior lesions was apparent on the post-operative WMI map relative to the pre-operative map. Lower GA at birth predicted an increasing volume of WMI across the full cohort (41.1 mm increase of WMI per week decrease in gestational age; 95% CI 11.5-70.8; p = 0.007), when accounting for centre and heart lesion. While WMI in term CHD and preterm neonates occurs most commonly in the intermediate zone/outer subventricular zone there is a paucity of central lesions in the CHD neonates relative to preterms.
WMI in term neonates with CHD occurs in a characteristic topology. The spatial distribution of WMI in term neonates with CHD reflects the expected maturation of pre-oligodendrocytes such that the central regions are less vulnerable than in the preterm neonates.
患有先天性心脏病 (CHD) 的新生儿有发生点状脑白质损伤 (WMI) 和脑发育受损的高风险。我们假设 CHD 新生儿的 WMI 呈特征性分布，与早产儿 WMI 的分布具有拓扑相似性，且出生胎龄 (GA) 越低，WMI 体积越大。
(1) 在三个中心定量评估 CHD 新生儿的 WMI 体积和位置。(2) 通过病灶图比较足月 CHD 新生儿和早产儿的 WMI 体积和空间分布。
在三个前瞻性队列中，216 名足月出生的 CHD 新生儿（平均出生 GA：39 周）中，86 名新生儿（UBC：29 名；UCSF：43 名；UCZ：14 名）在术前和/或术后 T1 加权 MRI 上发现了 WMI。手动分割 WMI 并计算体积。生成标准脑模板。在这个共同空间中开发了概率性 WMI 图（总 WMI、术前和术后）。使用这些地图，将足月 CHD 新生儿的 WMI 与早产儿的 WMI 进行比较：58 名新生儿在早期生命期（扫描时的平均孕龄为 32.2 周）；41 名新生儿在胎龄相等时（扫描时的平均孕龄为 40.1 周）。
各中心 CHD 新生儿的总 WMI 体积无差异（p=0.068）：UBC（中位数=84.6mm，IQR=26-174.7mm）；UCSF（中位数=104mm，IQR=44-243mm）；UCZ（中位数=121mm，IQR=68-200.8mm）。CHD 新生儿的 WMI 空间分布在各中心具有很强的一致性，倾向于出现前、后部病变，而不是中央病变。与术前 WMI 图相比，术后 WMI 图上的前病变更为明显。出生时 GA 越低，整个队列的 WMI 体积越大（GA 每减少一周，WMI 增加 41.1mm；95%CI 11.5-70.8；p=0.007），当考虑到中心和心脏病变时也是如此。虽然 CHD 足月新生儿和早产儿的 WMI 最常见于中间带/外 subventricular 区，但 CHD 新生儿的中央病变明显少于早产儿。
CHD 足月新生儿的 WMI 呈特征性拓扑分布。CHD 足月新生儿的 WMI 分布反映了前少突胶质细胞的预期成熟，使得中央区域比早产儿更不易受影响。
