Department of Maternal-Fetal Medicine, Institut Clinic de Ginecologia, Obstetricia i Neonatologia, Hospital Clinic, Barcelona, Spain.
PLoS One. 2012;7(2):e31497. doi: 10.1371/journal.pone.0031497. Epub 2012 Feb 8.
Intrauterine growth restriction (IUGR) affects 5-10% of all newborns and is associated with a high risk of abnormal neurodevelopment. The timing and patterns of brain reorganization underlying IUGR are poorly documented. We developed a rabbit model of IUGR allowing neonatal neurobehavioral assessment and high resolution brain diffusion magnetic resonance imaging (MRI). The aim of the study was to describe the pattern and functional correlates of fetal brain reorganization induced by IUGR.
METHODOLOGY/PRINCIPAL FINDINGS: IUGR was induced in 10 New Zealand fetal rabbits by ligation of 40-50% of uteroplacental vessels in one horn at 25 days of gestation. Ten contralateral horn fetuses were used as controls. Cesarean section was performed at 30 days (term 31 days). At postnatal day +1, neonates were assessed by validated neurobehavioral tests including evaluation of tone, spontaneous locomotion, reflex motor activity, motor responses to olfactory stimuli, and coordination of suck and swallow. Subsequently, brains were collected and fixed and MRI was performed using a high resolution acquisition scheme. Global and regional (manual delineation and voxel based analysis) diffusion tensor imaging parameters were analyzed. IUGR was associated with significantly poorer neurobehavioral performance in most domains. Voxel based analysis revealed fractional anisotropy (FA) differences in multiple brain regions of gray and white matter, including frontal, insular, occipital and temporal cortex, hippocampus, putamen, thalamus, claustrum, medial septal nucleus, anterior commissure, internal capsule, fimbria of hippocampus, medial lemniscus and olfactory tract. Regional FA changes were correlated with poorer outcome in neurobehavioral tests.
IUGR is associated with a complex pattern of brain reorganization already at birth, which may open opportunities for early intervention. Diffusion MRI can offer suitable imaging biomarkers to characterize and monitor brain reorganization due to fetal diseases.
宫内生长受限（IUGR）影响所有新生儿的 5-10%，并与异常神经发育的高风险相关。IUGR 下大脑重组的时间和模式记录不佳。我们开发了一种允许新生儿神经行为评估和高分辨率脑扩散磁共振成像（MRI）的兔 IUGR 模型。该研究的目的是描述由 IUGR 引起的胎儿大脑重组的模式和功能相关性。
方法/主要发现：在妊娠 25 天时，通过结扎一个子宫角中的 40-50%的胎盘血管，在 10 只新西兰胎儿兔中诱导 IUGR。10 只对侧子宫角胎儿用作对照。在 30 天（足月 31 天）时进行剖宫产。在产后第 1 天，通过验证的神经行为测试评估新生儿，包括评估音调、自发运动、反射运动活动、对嗅觉刺激的运动反应以及吸吮和吞咽的协调。随后，收集和固定大脑并进行 MRI 检查，使用高分辨率采集方案。分析全局和区域（手动描绘和体素分析）扩散张量成像参数。IUGR 与大多数领域的神经行为表现明显较差相关。体素分析显示，额叶、岛叶、枕叶和颞叶皮质、海马体、壳核、丘脑、屏状核、内侧隔核、前连合、内囊、海马回、内侧丘系和嗅束等灰质和白质的多个脑区的分数各向异性（FA）存在差异。区域 FA 变化与神经行为测试中的较差结果相关。
IUGR 出生时就与复杂的大脑重组模式相关，这可能为早期干预提供机会。扩散 MRI 可以提供合适的成像生物标志物，以表征和监测由于胎儿疾病导致的大脑重组。
