Claire E. Kelly

Alterations in the optic radiations of very preterm children—Perinatal predictors and relationships with visual outcomes

Children born very preterm (VPT) are at risk for visual impairments, the main risk factors being retinopathy of prematurity and cerebral white matter injury, however these only partially account for visual impairments in VPT children. This study aimed to compare optic radiation microstructure and volume between VPT and term-born children, and to investigate associations between 1) perinatal variables and optic radiations; 2) optic radiations and visual function in VPT children. We hypothesized that optic radiation microstructure would be altered in VPT children, predicted by neonatal cerebral white matter abnormality and retinopathy of prematurity, and associated with visual impairments. 142 VPT children and 32 controls underwent diffusion-weighted magnetic resonance imaging at 7 years of age. Optic radiations were delineated using constrained spherical deconvolution tractography. Tract volume and average diffusion tensor values for the whole optic radiations and three sub-regions were compared between the VPT and control groups, and correlated with perinatal variables and 7-year visual outcome data. Total tract volumes and average diffusion values were similar between VPT and control groups. On regional analysis of the optic radiation, mean and radial diffusivity were higher within the middle sub-regions in VPT compared with control children. Neonatal white matter abnormalities and retinopathy of prematurity were associated with optic radiation diffusion values. Lower fractional anisotropy in the anterior sub-regions was associated with poor visual acuity and increased likelihood of other visual defects. This study presents evidence for microstructural alterations in the optic radiations of VPT children, which are largely predicted by white matter abnormality or severe retinopathy of prematurity, and may partially explain the higher rate of visual impairments in VPT children.

A new neonatal cortical and subcortical brain atlas: the Melbourne Children's Regional Infant Brain (M-CRIB) atlas

ABSTRACT Investigating neonatal brain structure and function can offer valuable insights into behaviour and cognition in healthy and clinical populations; both at term age, and longitudinally in comparison with later time points. Parcellated brain atlases for adult populations are readily available, however warping infant data to adult template space is not ideal due to morphological and tissue differences between these groups. Several parcellated neonatal atlases have been developed, although there remains strong demand for manually parcellated ground truth data with detailed cortical definition. Additionally, compatibility with existing adult atlases is favourable for use in longitudinal investigations. We aimed to address these needs by replicating the widely‐used Desikan‐Killiany (2006) adult cortical atlas in neonates. We also aimed to extend brain coverage by complementing this cortical scheme with basal ganglia, thalamus, cerebellum and other subcortical segmentations. Thus, we have manually parcellated these areas volumetrically using high‐resolution neonatal T2‐weighted MRI scans, and initial automated and manually edited tissue classification, providing 100 regions in all. Linear and nonlinear T2‐weighted structural templates were also generated. In this paper we provide manual parcellation protocols, and present the parcellated probability maps and structural templates together as the Melbourne Childrens Regional Infant Brain (M‐CRIB) atlas. HIGHLIGHTSNovel cortical and subcortical atlas based on 10 neonatal T2 MRI scans.Volumetric replication of Desikan‐Killiany (2006) cortical atlas.Subcortical and cerebellar segmentations.Detailed manual parcellation provides valuable ground truth data.

Brain structural and microstructural alterations associated with cerebral palsy and motor impairments in adolescents born extremely preterm and/or extremely low birthweight

To elucidate neurobiological changes underlying motor impairments in adolescents born extremely preterm (gestation <28wks) and/or with extremely low birthweight (ELBW, <1000g), our aims were the following: (1) to compare corticospinal tract (CST) microstructure and primary motor cortex (M1) volume, area, and thickness between extremely preterm/ELBW adolescents and a comparison group with normal birthweight (>2499g); (2) to compare CST microstructure and M1 volume, area, and thickness between extremely preterm/ELBW adolescents with cerebral palsy (CP), motor impairment without CP, and no motor impairment; and (3) to investigate associations between CST microstructure and M1 measures.

Desikan-Killiany-Tourville Atlas Compatible Version of M-CRIB Neonatal Parcellated Whole Brain Atlas: The M-CRIB 2.0

Our recently published M-CRIB atlas comprises 100 neonatal brain regions including 68 compatible with the widely-used Desikan-Killiany adult cortical atlas. A successor to the Desikan-Killiany atlas is the Desikan-Killiany-Tourville atlas, in which some regions with unclear boundaries were removed, and many existing boundaries were revised to conform to clearer landmarks in sulcal fundi. Our first aim here was to modify cortical M-CRIB regions to comply with the Desikan-Killiany-Tourville protocol, in order to offer: a) compatibility with this adult cortical atlas, b) greater labelling accuracy due to clearer landmarks, and c) optimisation of cortical regions for integration with surface-based infant parcellation pipelines. Secondly, we aimed to update subcortical regions in order to offer greater compatibility with subcortical segmentations produced in FreeSurfer. Data utilized were the T2-weighted MRI scans in our M-CRIB atlas, for ten healthy neonates (postmenstrual age at MRI 40-43 weeks, 4 female), and corresponding parcellated images. Edits were performed on the parcellated images in volume space using ITK-SNAP. Cortical updates included deletion of frontal and temporal poles and ‘Banks STS’, and modification of boundaries of many other regions. Changes to subcortical regions included the addition of ‘ventral diencephalon’, and deletion of ‘subcortical matter’ labels. A detailed updated parcellation protocol was produced. The resulting whole-brain M-CRIB 2.0 atlas comprises 94 regions altogether. This atlas provides comparability with adult Desikan-Killiany-Tourville-labelled cortical data and FreeSurfer-labelled subcortical data, and is more readily adaptable for incorporation into surface-based neonatal parcellation pipelines. As such, it offers the ability to help facilitate a broad range of investigations into brain structure and function both at the neonatal time point and developmentally across the lifespan.

Changes in neonatal regional brain volume associated with preterm birth and perinatal factors

Background: Preterm birth is associated with altered brain development, with younger gestational age (GA) at birth often associated with greater brain volume reduction. Such volume alterations at term equivalent age (TEA) have been found with differing magnitude across different brain regions, although this has mostly been investigated with regards to whole tissue volumes and large‐scale subdivisions. In addition to degree of prematurity, many other perinatal factors have been found to influence brain structure and development in infants born preterm. We aimed to clarify the relationships between degree of prematurity and regional brain volumes at TEA, and between perinatal factors and regional brain volumes at TEA, in finer spatial detail. Methods: 285 preterm and term‐born infants (GA at birth 24.6–42.1 weeks; 145 female; 59 born at term) were scanned at TEA. Data on perinatal factors were obtained by chart review, including sex, multiple birth, birthweight standard deviation (SD) score, postnatal growth and social risk. The Melbourne Childrens Regional Infant Brain (M‐CRIB) atlas was registered to the current sample, then 100 brain regions were labelled for volumetric analyses. Linear regressions with generalised estimating equations and likelihood ratio tests were performed to investigate whether GA at birth or perinatal factors were associated with regional volumes at TEA. Results: Younger GA at birth was associated with smaller volumes at TEA in some regions including bilateral cerebral white matter, middle temporal gyri, amygdalae, pallidum and brainstem. In other regions, younger GA at birth was associated with larger volumes, including in primary visual, motor and somatosensory cortices. Positive associations between perinatal factors and regional volumes at TEA were found in many brain regions for birthweight SD score, and male sex, independent of GA at birth. These associations were seen on both univariable analyses, and multivariable analyses controlling for other perinatal factors. Social risk and multiple birth were generally not associated with regional brain volumes, and postnatal growth was associated with volume in many regions only after adjusting for other perinatal factors. Conclusions: These results elucidate regional brain volume differences associated with preterm birth and perinatal factors at a more detailed parcellated level than previously reported, and contribute to understanding of the complex array of correlates of preterm birth. HighlightsPreterm birth was associated with regional volume changes at term equivalent age.Of 100 regions measured, many were smaller with younger gestational age at birth.Unexpectedly, some regions were larger in infants born more preterm.Birthweight and male sex were strongly associated with larger regional volumes.

Caffeine for apnea of prematurity and brain development at 11 years of age

Caffeine therapy for apnea of prematurity has been reported to improve brain white matter microstructure at term‐equivalent age, but its long‐term effects are unknown. This study aimed to investigate whether caffeine affects (1) brain structure at 11 years of age, and (2) brain development from term‐equivalent age to 11 years of age, compared with placebo.