Measures obtained from diffusion-weighted imaging provide objective indices of white matter development and injury in the developing preterm brain. To date, diffusion tensor imaging (DTI) has been used widely, highlighting differences in fractional anisotropy (FA) and mean diffusivity (MD) between preterm infants at term and healthy term controls; altered white matter development associated with a number of perinatal risk factors; and correlations between FA values in the white matter in the neonatal period and subsequent neurodevelopmental outcome. Recent developments, including neurite orientation dispersion and density imaging (NODDI) and fixel-based analysis (FBA), enable white matter microstructure to be assessed in detail. Constrained spherical deconvolution (CSD) enables multiple fibre populations in an imaging voxel to be resolved and allows delineation of fibres that traverse regions of fibre-crossings, such as the arcuate fasciculus and cerebellar–cortical pathways. This review summarises DTI findings in the preterm brain and discusses initial findings in this population using CSD, NODDI, and FBA.

Infants with Congenital Heart Disease are at risk of neurodevelopmental impairments, the origins of which are currently unclear. The aim of this study was to characterise the relationship between neonatal brain development, cerebral oxygen delivery and neurodevelopmental outcome in infants with Congenital Heart Disease. A cohort of infants with serious or critical Congenital Heart Disease (N = 66; N = 62 born ≥37 weeks) underwent brain MRI prior to surgery on a 3 T scanner situated on the neonatal unit. T2-weighted images were segmented into brain regions using a neonatal-specific algorithm. We generated normative curves of typical volumetric brain development using a data-driven technique applied to 219 healthy infants from the Developing Human Connectome Project (dHCP). Atypicality indices, representing the degree of positive or negative deviation of a regional volume from the normative mean for a given gestational age, sex and postnatal age, were calculated for each infant with Congenital Heart Disease. Phase contrast angiography was acquired in 53 infants with Congenital Heart Disease and cerebral oxygen delivery was calculated. Cognitive and motor abilities were assessed at 22 months (N = 46) using the Bayley scales of Infant and Toddler Development—3rd Edition. We assessed the relationship between atypicality indices, cerebral oxygen delivery and cognitive and motor outcome. In addition, we examined whether cerebral oxygen delivery was associated with neurodevelopmental outcome through the mediating effect of brain volume. Negative atypicality indices in deep grey matter were associated with both reduced neonatal cerebral oxygen delivery and poorer cognitive abilities at 22 months across the whole sample. In infants with Congenital Heart Disease born ≥37 weeks negative cortical grey matter and total tissue volume atypicality indices, in addition to deep grey matter structures, were associated with poorer cognition. There was a significant indirect relationship between cerebral oxygen delivery and cognition through the mediating effect of negative deep grey matter atypicality indices across the whole sample. In infants born ≥37 weeks, cortical grey matter and total tissue volume atypicality indices were also mediators of this relationship. In summary, lower cognitive abilities in toddlers with Congenital Heart Disease were associated with smaller grey matter volumes prior to cardiac surgery. The aetiology of poor cognition may encompass poor cerebral oxygen delivery leading to impaired grey matter growth. Interventions to improve cerebral oxygen delivery may promote early brain growth and improve cognitive outcomes in infants with Congenital Heart Disease. Bonthrone et al. assessed individualized brain growth in infants with congenital heart disease compared to a large normative sample to determine atypicality indices in the patient group. Low cerebral oxygen delivery was associated with impaired grey matter development and resulted in poor cognitive outcome in this population.

Magnetic resonance (MR) imaging studies have demonstrated reduced global and regional brain volumes in infants with congenital heart disease (CHD). This study aimed to provide a more detailed evaluation of altered structural brain development in newborn infants with CHD compared to healthy controls using tensor-based morphometry (TBM). We compared brain development in 64 infants with CHD to 192 age- and sex-matched healthy controls. T2-weighted MR images obtained prior to surgery were analysed to compare voxel-wise differences in structure across the whole brain between groups. Cerebral oxygen delivery (CDO2) was measured in infants with CHD (n = 49) using phase contrast MR imaging and the relationship between CDO2 and voxel-wise brain structure was assessed using TBM. After correcting for global scaling differences, clusters of significant volume reduction in infants with CHD were demonstrated bilaterally within the basal ganglia, thalami, corpus callosum, occipital, temporal, parietal and frontal lobes, and right hippocampus (p < 0.025 after family-wise error correction). Clusters of significant volume expansion in infants with CHD were identified in cerebrospinal fluid spaces (p < 0.025). After correcting for global brain size, there was no significant association between voxel-wise brain structure and CDO2. This study localizes abnormal brain development in infants with CHD, identifying areas of particular vulnerability.

FOXP2 is the major gene associated with severe, persistent, developmental speech and language disorders. While studies in the original family in which a FOXP2 mutation was found showed volume reduction and reduced activation in core language and speech networks, there have been no imaging studies of different FOXP2 mutations. We conducted a multimodal MRI study in an eight-year-old boy (A-II) with a de novo FOXP2 intragenic deletion. A-II showed marked bilateral volume reductions in the hippocampus, thalamus, globus pallidus, and caudate nucleus compared with 26 control males (effect sizes from −1 to −3). He showed no detectable functional MRI activity when repeating nonsense words. The hippocampus is implicated for the first time in FOXP2 diseases. We conclude that FOXP2 anomaly is either directly or indirectly associated with atypical development of widespread subcortical networks early in life.

Highlights A subnetwork with reduced structural connectivity was identified in infants with CHD. This subnetwork comprised regions predominantly in the cortico-striatal-thalamic network. Core nodes and core edges were mostly affected in this subnetwork. Global network features were not significantly different in CHD group.