Maternal choline supplementation mitigates alcohol exposure effects on neonatal brain volumes.

BACKGROUND: Prenatal alcohol exposure (PAE) is associated with smaller regional and global brain volumes. In rats, gestational choline supplementation mitigates adverse developmental effects of ethanol exposure. Our recent randomized, double-blind, placebo-controlled maternal choline supplementation trial showed improved somatic and functional outcomes in infants at 6.5 and 12 months postpartum. Here, we examined whether maternal choline supplementation protected the newborn brain from PAE-related volume reductions and, if so, whether these volume changes were associated with improved infant recognition memory. METHODS: Fifty-two infants born to heavy-drinking women who had participated in a choline supplementation trial during pregnancy underwent structural magnetic resonance imaging with a multi-echo FLASH protocol on a 3T Siemens Allegra MRI (median age = 2.8 weeks postpartum). Subcortical regions were manually segmented. Recognition memory was assessed at 12 months on the Fagan Test of Infant Intelligence (FTII). We examined the effects of choline on regional brain volumes, whether choline-related volume increases were associated with higher FTII scores, and the degree to which the regional volume increases mediated the effects of choline on the FTII. RESULTS: Usable MRI data were acquired in 50 infants (choline: n = 27; placebo: n = 23). Normalized volumes were larger in six of 12 regions in the choline than placebo arm (t ≥ 2.05, p ≤ 0.05) and were correlated with the degree of maternal choline adherence (ß ≥ 0.28, p ≤ 0.04). Larger right putamen and corpus callosum were related to higher FTII scores (r = 0.36, p = 0.02) with a trend toward partial mediation of the choline effect on recognition memory. CONCLUSIONS: High-dose choline supplementation during pregnancy mitigated PAE-related regional volume reductions, with larger volumes associated with improved 12-month recognition memory. These results provide the first evidence that choline may be neuroprotective against PAE-related brain structural deficits in humans.

System-Specific Patterns of Thalamocortical Connectivity in Early Brain Development as Revealed by Structural and Functional MRI.

The normal development of thalamocortical connections plays a critical role in shaping brain connectivity in the prenatal and postnatal periods. Recent studies using advanced magnetic resonance imaging (MRI) techniques in neonates and infants have shown that abnormal thalamocortical connectivity is associated with adverse neurodevelopmental outcomes. However, all these studies have focused on a single neuroimaging modality, overlooking the dynamic relationship between structure and function at this early stage. Here, we study the relationship between structural and functional thalamocortical connectivity patterns derived from healthy full-term infants scanned with diffusion-weighted MRI and resting-state functional MRI within the first weeks of life (mean gestational age = 39.3 ± 1.2 weeks; age at scan = 24.2 ± 7.9 days). Our results show that while there is, in general, good spatial agreement between both MRI modalities, there are regional variations that are system-specific: regions involving primary-sensory cortices exhibit greater structural/functional overlap, whereas higher-order association areas such as temporal and posterior parietal cortices show divergence in spatial patterns of each modality. This variability illustrates the complementarity of both modalities and highlights the importance of multimodal approaches.

Probabilistic tractography-based thalamic parcellation in healthy newborns and newborns with congenital heart disease.

BACKGROUND: Given the central role of the thalamus in motor, sensory, and cognitive development, methods to study emerging thalamocortical connectivity in early infancy are of great interest. PURPOSE: To determine the feasibility of performing probabilistic tractography-based thalamic parcellation (PTbTP) in typically developing (TD) neonates and to compare the results with a pilot sample of neonates with congenital heart disease (CHD). STUDY TYPE: Institutional Review Board (IRB)-approved cross-sectional study. MODEL: We prospectively recruited 20 TD neonates and five CHD neonates (imaged preoperatively). FIELD STRENGTH/SEQUENCE: MRI was performed at 3.0T including diffusion-weighted imaging (DWI) and 3D magnetization prepared rapid gradient-echo (MPRAGE). ASSESSMENT: A radiologist and trained research assistants segmented the thalamus and seven cortical targets for each hemisphere. Using the thalami as seeds and the cortical labels as targets, FSL library tools were used to generate probabilistic tracts. A Hierarchical Dirichlet Process algorithm was then used for clustering analysis. A radiologist qualitatively assessed the results of clustering. Quantitative analyses were also performed. STATISTICAL TESTS: We summarized the demographic data and results of clustering with descriptive statistics. Linear regressions covarying for gestational age were used to compare groups. RESULTS: In 17 of 20 TD neonates, we identified five connectivity-determined clusters, which correlate with known thalamic nuclei and subnuclei. In four neonates with CHD we observed a spectrum of abnormalities including fewer and disorganized clusters or small supernumerary clusters (up to seven per thalamus). After covarying for differences in corrected gestational age (cGA), the fractional anisotropy (FA), volume, and normalized thalamic volume were significantly lower in CHD neonates (P < 0.01). DATA CONCLUSIONS: Using PTbTP clusters, correlating well with the location and connectivity of known thalamic nuclei, were identified in TD neonates. Differences in thalamic clustering outputs were identified in four neonates with CHD, raising concern for disordered thalamic connectivity. PTbTP is feasible in TD and CHD neonates. Preliminary findings suggest the prenatal origins of altered connectivity in CHD. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018;47:1626-1637.

Prenatal methamphetamine exposure is associated with reduced subcortical volumes in neonates.

OBJECTIVES: Prenatal exposure to methamphetamine is associated with a range of neuropsychological, behavioural and cognitive deficits. A small number of imaging studies suggests that these may be mediated by neurostructural changes, including reduced volumes of specific brain regions. This study investigated potential volumetric changes in the brains of neonates with prenatal methamphetamine exposure. To our knowledge no previous studies have examined methamphetamine effects on regional brain volumes at this age. STUDY DESIGN: Mothers were recruited antenatally and interviewed regarding methamphetamine use during pregnancy. Mothers in the exposure group reported using methamphetamine≥twice/month during pregnancy; control infants had no exposure to methamphetamine or other drugs and minimal exposure to alcohol. MRI scans were performed in the first postnatal month, following which anatomical images were processed using FreeSurfer. Subcortical and cerebellar regions were manually segmented and their volumes determined using FreeView. Pearson correlations were used to analyse potential associations between methamphetamine exposure and regional volumes. The associations between methamphetamine exposure and regional volumes were then examined adjusting for potential confounding variables. RESULTS: Methamphetamine exposure was associated with reduced left and right caudate and thalamus volumes. The association in the right caudate remained significant following adjustment for potential confounding variables. CONCLUSIONS: Our findings showing reduced caudate and thalamus volumes in neonates with prenatal methamphetamine exposure are consistent with previous findings in older exposed children, and demonstrate that these changes are already detectable in neonates. Continuing research is warranted to examine whether reduced subcortical volumes are predictive of cognitive, behavioural and affective impairment in older children.

Evaluating volumetric brain registration performance using structural connectivity information.

In this paper, we propose a pipeline for evaluating the performance of brain image registration methods. Our aim is to compare how well the algorithms align subtle functional/anatomical boundaries that are not easily detectable in T1- or T2-weighted magnetic resonance images (MRI). In order to achieve this, we use structural connectivity information derived from diffusion-weighted MRI data. We demonstrate the approach by looking into how two competing registration algorithms perform at aligning fine-grained parcellations of subcortical structures. The results show that the proposed evaluation framework can offer new insights into the performance of registration algorithms in brain regions with highly varied structural connectivity profiles.