Structural connectivity relates to perinatal factors and functional impairment at 7years in children born very preterm.

OBJECTIVE: To use structural connectivity to (1) compare brain networks between typically and atypically developing (very preterm) children, (2) explore associations between potential perinatal developmental disturbances and brain networks, and (3) describe associations between brain networks and functional impairments in very preterm children. METHODS: 26 full-term and 107 very preterm 7-year-old children (born <30weeks' gestational age and/or <1250g) underwent T1- and diffusion-weighted imaging. Global white matter fibre networks were produced using 80 cortical and subcortical nodes, and edges were created using constrained spherical deconvolution-based tractography. Global graph theory metrics were analysed, and regional networks were identified using network-based statistics. Cognitive and motor function were assessed at 7years of age. RESULTS: Compared with full-term children, very preterm children had reduced density, lower global efficiency and higher local efficiency. Those with lower gestational age at birth, infection or higher neonatal brain abnormality score had reduced connectivity. Reduced connectivity within a widespread network was predictive of impaired IQ, while reduced connectivity within the right parietal and temporal lobes was associated with motor impairment in very preterm children. CONCLUSIONS: This study utilised an innovative structural connectivity pipeline to reveal that children born very preterm have less connected and less complex brain networks compared with typically developing term-born children. Adverse perinatal factors led to disturbances in white matter connectivity, which in turn are associated with impaired functional outcomes, highlighting novel structure-function relationships.

A New MRI-Based Pediatric Subcortical Segmentation Technique (PSST).

Volumetric and morphometric neuroimaging studies of the basal ganglia and thalamus in pediatric populations have utilized existing automated segmentation tools including FIRST (Functional Magnetic Resonance Imaging of the Brain's Integrated Registration and Segmentation Tool) and FreeSurfer. These segmentation packages, however, are mostly based on adult training data. Given that there are marked differences between the pediatric and adult brain, it is likely an age-specific segmentation technique will produce more accurate segmentation results. In this study, we describe a new automated segmentation technique for analysis of 7-year-old basal ganglia and thalamus, called Pediatric Subcortical Segmentation Technique (PSST). PSST consists of a probabilistic 7-year-old subcortical gray matter atlas (accumbens, caudate, pallidum, putamen and thalamus) combined with a customized segmentation pipeline using existing tools: ANTs (Advanced Normalization Tools) and SPM (Statistical Parametric Mapping). The segmentation accuracy of PSST in 7-year-old data was compared against FIRST and FreeSurfer, relative to manual segmentation as the ground truth, utilizing spatial overlap (Dice's coefficient), volume correlation (intraclass correlation coefficient, ICC) and limits of agreement (Bland-Altman plots). PSST achieved spatial overlap scores ≥90% and ICC scores ≥0.77 when compared with manual segmentation, for all structures except the accumbens. Compared with FIRST and FreeSurfer, PSST showed higher spatial overlap (p FDR < 0.05) and ICC scores, with less volumetric bias according to Bland-Altman plots. PSST is a customized segmentation pipeline with an age-specific atlas that accurately segments typical and atypical basal ganglia and thalami at age 7 years, and has the potential to be applied to other pediatric datasets.

High Postnatal Growth Hormone Levels Are Related to Cognitive Deficits in a Group of Children Born Very Preterm.

CONTEXT AND OBJECTIVES: Little is known regarding the influence of GH on brain development, especially in infants born very preterm (VP; <30 weeks' gestation). Preterm infants are thought to have higher levels of GH in the first days of life compared with full-term infants. VP infants experience cognitive difficulties in childhood and have a diffuse pattern of structural brain abnormalities. This study aimed to explore the relationship between postnatal GH concentrations following VP birth and its association with cognitive functioning and brain volumes at age 7 years. METHODS: Eighty-three infants born VP had GH concentrations measured at eight time points postnatally, and 2- and 6-week area under the curve (AUC) summary measures were calculated. Followup at age 7 years included neuropsychological assessment and brain magnetic resonance imaging. Univariable and multivariable regression modeling were used where AUC for GH was the main predictor of neurodevelopmental outcome at age 7 years. RESULTS: Univariable modeling revealed that higher GH levels (2-week AUC) were related to poorer performance on a verbal working memory (P = .04) and shifting attention task (P = .01). These relationships persisted on multivariable modeling and when the 6-week AUC was analyzed; working memory (P = .03), immediate spatial memory (P = .02), and delayed spatial memory (P = .03) deficits were found. Higher GH levels were also associated with larger amygdala volumes after adjustment for potential confounders (P = .002, 2-week AUC; P = .03, 6-week AUC). CONCLUSIONS: Higher postnatal GH levels may potentially contribute to the documented neurodevelopmental abnormalities seen in children born VP at school age.

Free thyroxine levels after very preterm birth and neurodevelopmental outcomes at age 7 years.

BACKGROUND AND OBJECTIVES: Preterm infants commonly have transient hypothyroxinemia of prematurity after birth, which has been associated with deficits in general intellectual functioning, memory, attention, and academic achievement. However, research has predominantly focused on thyroxine levels in the first 2 weeks of life and outcomes are limited to the preschool period. Our objective was to evaluate the relationships between free thyroxine (fT4) levels over the first 6 weeks after very preterm (VPT) birth with cognitive functioning and brain development at age 7 years. METHODS: A total of 83 infants born VPT (<30 weeks' gestation) had fT4 concentrations measured postnatally and 2- and 6-week area under the curve (AUC) summary measures were calculated. Follow-up at age 7 years included a neuropsychological assessment and brain MRI. Univariable and multivariable regression modeling was used where AUC for fT4 was the main predictor of neurodevelopmental outcome at age 7 years. RESULTS: Multivariable modeling revealed that higher, not lower, postnatal fT4 levels (2-week AUC) were associated with poorer cognitive performances at age 7 years on tasks of verbal learning (P = .02), verbal memory (P = .03), and simple reaction time (P < .001). A similar pattern of results was found when the 6-week AUC was examined. No significant associations between postnatal fT4 levels and brain volumes at age 7 years were identified. CONCLUSIONS: Results are contradictory to previous observations and suggest that after adjustment for confounders, higher postnatal fT4 levels in VPT infants, rather than lower levels, may be a marker of adverse neuropsychological development in childhood.

Optimizing hippocampal segmentation in infants utilizing MRI post-acquisition processing.

This study aims to determine the most reliable method for infant hippocampal segmentation by comparing magnetic resonance (MR) imaging post-acquisition processing techniques: contrast to noise ratio (CNR) enhancement, or reformatting to standard orientation. MR scans were performed with a 1.5 T GE scanner to obtain dual echo T2 and proton density (PD) images at term equivalent (38-42 weeks' gestational age). 15 hippocampi were manually traced four times on ten infant images by 2 independent raters on the original T2 image, as well as images processed by: a) combining T2 and PD images (T2-PD) to enhance CNR; then b) reformatting T2-PD images perpendicular to the long axis of the left hippocampus. CNRs and intraclass correlation coefficients (ICC) were calculated. T2-PD images had 17% higher CNR (15.2) than T2 images (12.6). Original T2 volumes' ICC was 0.87 for rater 1 and 0.84 for rater 2, whereas T2-PD images' ICC was 0.95 for rater 1 and 0.87 for rater 2. Reliability of hippocampal segmentation on T2-PD images was not improved by reformatting images (rater 1 ICC = 0.88, rater 2 ICC = 0.66). Post-acquisition processing can improve CNR and hence reliability of hippocampal segmentation in neonate MR scans when tissue contrast is poor. These findings may be applied to enhance boundary definition in infant segmentation for various brain structures or in any volumetric study where image contrast is sub-optimal, enabling hippocampal structure-function relationships to be explored.