Fetal i+D Fetal Medicine Research Center, BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, Barcelona, Spain; Centre for Biomedical Research on Rare Diseases, Barcelona, Spain.
Fetal i+D Fetal Medicine Research Center, BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, Barcelona, Spain.
Am J Obstet Gynecol. 2016 Jun;214(6):725.e1-9. doi: 10.1016/j.ajog.2015.12.028. Epub 2015 Dec 21.
Intrauterine growth restriction is associated with short- and long-term neurodevelopmental problems. Structural brain changes underlying these alterations have been described with the use of different magnetic resonance-based methods that include changes in whole structural brain networks. However, evaluation of specific brain circuits and its correlation with related functions has not been investigated in intrauterine growth restriction.
In this study, we aimed to investigate differences in tractography-related metrics in cortico-striatal-thalamic and motor networks in intrauterine growth restricted children and whether these parameters were related with their specific function in order to explore its potential use as an imaging biomarker of altered neurodevelopment.
We included a group of 24 intrauterine growth restriction subjects and 27 control subjects that were scanned at 1 year old; we acquired T1-weighted and 30 directions diffusion magnetic resonance images. Each subject brain was segmented in 93 regions with the use of anatomical automatic labeling atlas, and deterministic tractography was performed. Brain regions included in motor and cortico-striatal-thalamic networks were defined based in functional and anatomic criteria. Within the streamlines that resulted from the whole brain tractography, those belonging to each specific circuit were selected and tractography-related metrics that included number of streamlines, fractional anisotropy, and integrity were calculated for each network. We evaluated differences between both groups and further explored the correlation of these parameters with the results of socioemotional, cognitive, and motor scales from Bayley Scale at 2 years of age.
Reduced fractional anisotropy (cortico-striatal-thalamic, 0.319 ± 0.018 vs 0.315 ± 0.015; P = .010; motor, 0.322 ± 0.019 vs 0.319 ± 0.020; P = .019) and integrity cortico-striatal-thalamic (0.407 ± 0.040 vs 0.399 ± 0.034; P = .018; motor, 0.417 ± 0.044 vs 0.409 ± 0.046; P = .016) in both networks were observed in the intrauterine growth restriction group, with no differences in number of streamlines. More importantly, strong specific correlation was found between tractography-related metrics and its relative function in both networks in intrauterine growth restricted children. Motor network metrics were correlated specifically with motor scale results (fractional anisotropy: rho = 0.857; integrity: rho = 0.740); cortico-striatal-thalamic network metrics were correlated with cognitive (fractional anisotropy: rho = 0.793; integrity, rho = 0.762) and socioemotional scale (fractional anisotropy: rho = 0.850; integrity: rho = 0.877).
These results support the existence of altered brain connectivity in intrauterine growth restriction demonstrated by altered connectivity in motor and cortico-striatal-thalamic networks, with reduced fractional anisotropy and integrity. The specific correlation between tractography-related metrics and neurodevelopmental outcomes in intrauterine growth restriction shows the potential to use this approach to develop imaging biomarkers to predict specific neurodevelopmental outcome in infants who are at risk because of intrauterine growth restriction and other prenatal diseases.
宫内生长受限与短期和长期神经发育问题有关。使用不同的基于磁共振的方法描述了这些改变背后的结构脑变化，这些方法包括整个结构脑网络的改变。然而，在宫内生长受限中，尚未研究特定脑回路的评估及其与相关功能的相关性。
本研究旨在探讨宫内生长受限儿童皮质-纹状体-丘脑和运动网络中追踪相关指标的差异，以及这些参数是否与他们的特定功能相关，以探索其作为神经发育改变的潜在影像学生物标志物的用途。
我们纳入了一组 24 名宫内生长受限的儿童和 27 名对照组儿童，他们在 1 岁时进行了 T1 加权和 30 个方向的弥散磁共振成像。使用解剖自动标记图谱对每个受试者的大脑进行 93 个区域的分割，并进行确定性追踪。根据功能和解剖标准定义了运动和皮质-纹状体-丘脑网络中包含的脑区。在整个大脑追踪产生的轨迹中，选择属于每个特定回路的轨迹，并计算每个网络的轨迹相关指标，包括轨迹数、各向异性分数和完整性。我们评估了两组之间的差异，并进一步探索了这些参数与贝利婴幼儿发展量表（Bayley Scale）2 岁时的社会情感、认知和运动量表结果之间的相关性。
我们观察到宫内生长受限组皮质-纹状体-丘脑网络（0.319 ± 0.018 比 0.315 ± 0.015；P =.010；运动网络，0.322 ± 0.019 比 0.319 ± 0.020；P =.019）和皮质-纹状体-丘脑网络（0.407 ± 0.040 比 0.399 ± 0.034；P =.018；运动网络，0.417 ± 0.044 比 0.409 ± 0.046；P =.016）的各向异性分数（fractional anisotropy，FA）和完整性均降低，而轨迹数量没有差异。更重要的是，我们在宫内生长受限儿童中发现了这两个网络中追踪相关指标与其相对功能之间存在强烈的特定相关性。运动网络的指标与运动量表的结果（FA：rho = 0.857；完整性：rho = 0.740）具有特异性相关；皮质-纹状体-丘脑网络的指标与认知（FA：rho = 0.793；完整性，rho = 0.762）和社会情感量表（FA：rho = 0.850；完整性：rho = 0.877）具有相关性。
这些结果支持宫内生长受限存在改变的脑连接，表现为运动和皮质-纹状体-丘脑网络中连接的改变，伴有各向异性分数和完整性的降低。宫内生长受限中追踪相关指标与神经发育结果之间的特定相关性表明，这种方法有可能用于开发影像学生物标志物，以预测因宫内生长受限和其他产前疾病而处于风险中的婴儿的特定神经发育结果。
