Department of Maternal-Fetal Medicine, Institut Clinic de Ginecologia, Obstetricia i Neonatologia (ICGON), Hospital Clinic, Barcelona, Spain ; Fetal and Perinatal Medicine Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
PLoS One. 2013 Oct 15;8(10):e76453. doi: 10.1371/journal.pone.0076453. eCollection 2013.
Intrauterine growth restriction (IUGR) affects 5-10% of all newborns and is associated with increased risk of memory, attention and anxiety problems in late childhood and adolescence. The neurostructural correlates of long-term abnormal neurodevelopment associated with IUGR are unknown. Thus, the aim of this study was to provide a comprehensive description of the long-term functional and neurostructural correlates of abnormal neurodevelopment associated with IUGR in a near-term rabbit model (delivered at 30 days of gestation) and evaluate the development of quantitative imaging biomarkers of abnormal neurodevelopment based on diffusion magnetic resonance imaging (MRI) parameters and connectivity.
At +70 postnatal days, 10 cases and 11 controls were functionally evaluated with the Open Field Behavioral Test which evaluates anxiety and attention and the Object Recognition Task that evaluates short-term memory and attention. Subsequently, brains were collected, fixed and a high resolution MRI was performed. Differences in diffusion parameters were analyzed by means of voxel-based and connectivity analysis measuring the number of fibers reconstructed within anxiety, attention and short-term memory networks over the total fibers.
The results of the neurobehavioral and cognitive assessment showed a significant higher degree of anxiety, attention and memory problems in cases compared to controls in most of the variables explored. Voxel-based analysis (VBA) revealed significant differences between groups in multiple brain regions mainly in grey matter structures, whereas connectivity analysis demonstrated lower ratios of fibers within the networks in cases, reaching the statistical significance only in the left hemisphere for both networks. Finally, VBA and connectivity results were also correlated with functional outcome.
The rabbit model used reproduced long-term functional impairments and their neurostructural correlates of abnormal neurodevelopment associated with IUGR. The description of the pattern of microstructural changes underlying functional defects may help to develop biomarkers based in diffusion MRI and connectivity analysis.
宫内生长受限（IUGR）影响所有新生儿的 5-10%，与儿童晚期和青春期记忆、注意力和焦虑问题的风险增加有关。与 IUGR 相关的长期异常神经发育的神经结构相关性尚不清楚。因此，本研究的目的是在接近足月的兔模型（妊娠 30 天分娩）中提供与 IUGR 相关的异常神经发育的长期功能和神经结构相关性的综合描述，并评估基于扩散磁共振成像（MRI）参数和连接的异常神经发育定量成像生物标志物的发展。
在出生后 70 天，10 例病例和 11 例对照通过开放场行为测试进行功能评估，该测试评估焦虑和注意力，以及评估短期记忆和注意力的物体识别任务。随后，收集大脑、固定并进行高分辨率 MRI 检查。通过基于体素和连接分析来分析扩散参数的差异，通过在整个纤维中重建焦虑、注意力和短期记忆网络内的纤维数量来测量纤维的数量。
神经行为和认知评估的结果表明，与对照组相比，病例组在大多数探索变量中表现出明显更高程度的焦虑、注意力和记忆问题。基于体素的分析（VBA）显示两组之间存在多个脑区的显著差异，主要是在灰质结构中，而连接分析显示病例组网络内的纤维比例较低，仅在两个网络的左半球达到统计学意义。最后，VBA 和连接结果也与功能结果相关。
所使用的兔模型再现了与 IUGR 相关的长期功能障碍及其异常神经发育的神经结构相关性。描述功能缺陷下的微观结构变化模式可能有助于基于扩散 MRI 和连接分析开发生物标志物。
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