Human cortical development during the third trimester is characterised by macro- and microstructural changes which are reflected in alterations in diffusion MRI (dMRI) measures, with significant ...decreases in cortical mean diffusivity (MD) and fractional anisotropy (FA). This has been interpreted as reflecting increased cellular density and dendritic arborisation. However, the fall in FA stops abruptly at 38 weeks post-menstrual age (PMA), and then tends to plateau, while MD continues to fall, suggesting a more complex picture and raising the hypothesis that after this age development is dominated by continuing increase in neural and organelle density rather than alterations in the geometry of dendritic trees. To test this, we used neurite orientation dispersion and density imaging (NODDI), acquiring multi-shell, high angular resolution dMRI and measures of cortical volume and mean curvature in 99 preterm infants scanned between 25 and 47 weeks PMA. We predicted that increased neurite and organelle density would be reflected in increases in neurite density index (NDI), while a relatively unchanging geometrical structure would be associated with constant orientation dispersion index (ODI). As dendritic arborisation is likely to be one of the drivers of gyrification, we also predicted that measures of cortical volume and curvature would correlate with ODI and show slower growth after 38 weeks.
We observed a decrease of MD throughout the period, while cortical FA decreased from 25 to 38 weeks PMA and then increased. ODI increased up to 38 weeks and then plateaued, while NDI rose after 38 weeks. The evolution of ODI correlated with cortical volume and curvature. Regional analysis of cortical microstructure revealed a heterogenous pattern with increases in FA and NDI after 38 weeks confined to primary motor and sensory regions. These results support the interpretation that cortical development between 25 and 38 weeks PMA shows a predominant increase in dendritic arborisation and neurite growth, while between 38 and 47 weeks PMA it is dominated by increasing cellular and organelle density.
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•DTI and NODDI cortical measures between 25 and 47 weeks GA•Early cortical changes consistent with dendritic arborisation and neurite growth•After 38 weeks cortical changes consistent with increasing cellular density•Cortical curvature evolves in parallel with dendritic arborisation
A dedicated neonatal brain imaging system Hughes, Emer J.; Winchman, Tobias; Padormo, Francesco ...
Magnetic resonance in medicine,
August 2017, Letnik:
78, Številka:
2
Journal Article
•Subject motion in dMRI leads to a set of scattered slices with unique contrast.•We introduce a slice-to-volume reconstruction framework for multi-shell HARDI data•Based on a data-driven ...representation as spherical harmonics and radial decomposition (SHARD).•The method is evaluated in test-retest scans and in the neonatal dHCP cohort.•Results show robust reconstruction in severely motion-corrupted scans.
Diffusion MRI offers a unique probe into neural microstructure and connectivity in the developing brain. However, analysis of neonatal brain imaging data is complicated by inevitable subject motion, leading to a series of scattered slices that need to be aligned within and across diffusion-weighted contrasts. Here, we develop a reconstruction method for scattered slice multi-shell high angular resolution diffusion imaging (HARDI) data, jointly estimating an uncorrupted data representation and motion parameters at the slice or multiband excitation level. The reconstruction relies on data-driven representation of multi-shell HARDI data using a bespoke spherical harmonics and radial decomposition (SHARD), which avoids imposing model assumptions, thus facilitating to compare various microstructure imaging methods in the reconstructed output. Furthermore, the proposed framework integrates slice-level outlier rejection, distortion correction, and slice profile correction. We evaluate the method in the neonatal cohort of the developing Human Connectome Project (650 scans). Validation experiments demonstrate accurate slice-level motion correction across the age range and across the range of motion in the population. Results in the neonatal data show successful reconstruction even in severely motion-corrupted subjects. In addition, we illustrate how local tissue modelling can extract advanced microstructure features such as orientation distribution functions from the motion-corrected reconstructions.
Preterm infants are at high risk of neurodevelopmental impairment, which may be due to altered development of brain connectivity. We aimed to (i) assess structural brain development from 25 to 45 ...weeks gestational age (GA) using graph theoretical approaches and (ii) test the hypothesis that preterm birth results in altered white matter network topology. Sixty-five infants underwent MRI between 25+3 and 45+6 weeks GA. Structural networks were constructed using constrained spherical deconvolution tractography and were weighted by measures of white matter microstructure (fractional anisotropy, neurite density and orientation dispersion index). We observed regional differences in brain maturation, with connections to and from deep grey matter showing most rapid developmental changes during this period. Intra-frontal, frontal to cingulate, frontal to caudate and inter-hemispheric connections matured more slowly. We demonstrated a core of key connections that was not affected by GA at birth. However, local connectivity involving thalamus, cerebellum, superior frontal lobe, cingulate gyrus and short range cortico-cortical connections was related to the degree of prematurity and contributed to altered global topology of the structural brain network. The relative preservation of core connections at the expense of local connections may support more effective use of impaired white matter reserve following preterm birth.
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•First characterisation of preterm brain networks weighted by microstructural features.•Preterm brain is resistant to disruptions in development of core connections.•Peripheral connections associated with cognition and behaviour are more vulnerable.
During the second and third trimesters of human gestation, rapid neurodevelopment is underpinned by fundamental processes including neuronal migration, cellular organization, cortical layering, and ...myelination. In this time, white matter growth and maturation lay the foundation for an efficient network of structural connections. Detailed knowledge about this developmental trajectory in the healthy human fetal brain is limited, in part, due to the inherent challenges of acquiring high-quality MRI data from this population. Here, we use state-of-the-art high-resolution multishell motion-corrected diffusion-weighted MRI (dMRI), collected as part of the developing Human Connectome Project (dHCP), to characterize the in utero maturation of white matter microstructure in 113 fetuses aged 22 to 37 wk gestation. We define five major white matter bundles and characterize their microstructural features using both traditional diffusion tensor and multishell multitissue models. We found unique maturational trends in thalamocortical fibers compared with association tracts and identified different maturational trends within specific sections of the corpus callosum. While linear maturational increases in fractional anisotropy were seen in the splenium of the corpus callosum, complex nonlinear trends were seen in the majority of other white matter tracts, with an initial decrease in fractional anisotropy in early gestation followed by a later increase. The latter is of particular interest as it differs markedly from the trends previously described in ex utero preterm infants, suggesting that this normative fetal data can provide significant insights into the abnormalities in connectivity which underlie the neurodevelopmental impairments associated with preterm birth.
The thalamus undergoes significant volume loss and microstructural change with increasing age. Alterations in thalamo-cortical connectivity may contribute to the decline in cognitive ability ...associated with aging. The aim of this study was to assess changes in thalamic shape and in the volume and diffusivity of thalamic regions parcellated by their connectivity to specific cortical regions in order to test the hypothesis age related thalamic change primarily affects thalamic nuclei connecting to the frontal cortex.
Using structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI), we assessed thalamic volume and diffusivity in 86 healthy volunteers, median (range) age 44 (20–74) years. Regional thalamic micro and macro structural changes were assessed by segmenting the thalamus based on connectivity to the frontal, parietal, temporal and occipital cortices and determining the volumes and mean diffusivity of the thalamic projections.
Linear regression analysis was performed to test the relationship between increasing age and (i) normalised thalamic volume, (ii) whole thalamus diffusion measures, (iii) mean diffusivity (MD) of the thalamo-cortical projections, and (iv) volumes of the thalamo-cortical projections. We also assessed thalamic shape change using vertex analysis.
We observed a significant reduction in the volume and a significant increase in MD of the whole thalamus with increasing age. The volume of the thalamo-frontal projections decreased significantly with increasing age, however there was no significant relationship between the volumes of the thalamo-cortical projections to the parietal, temporal, and occipital cortex and age. Thalamic shape analysis showed that the greatest shape change was in the anterior thalamus, incorporating regions containing the anterior nucleus, the ventroanterior nucleus and the dorsomedial nucleus. To explore these results further we studied two additional groups of subjects (a younger and an older aged group, n=20), which showed that the volume of the thalamo-frontal projections was correlated to executive functions scores, as assessed by the Stroop test. These data suggest that atrophy of the frontal thalamo-cortical unit may explain, at least in part, disorders of attention, working memory and executive function associated with increasing age.
•First simultaneous measurement of GABA+, Glx and GSH in the neonatal human brain.•Robust metabolic estimation in neonates requires a specific quantification strategy.•GABA+ has a doublet peak in ...neonates indicating lower macromolecular contributions.•Future application can inform about pathophysiology in neurodevelopment.
Balance between inhibitory and excitatory neurotransmitter systems and the protective role of the major antioxidant glutathione (GSH) are central to early healthy brain development. Disruption has been implicated in the early life pathophysiology of psychiatric disorders and neurodevelopmental conditions including Autism Spectrum Disorder.
Edited magnetic resonance spectroscopy (MRS) methods such as HERMES have great potential for providing important new non-invasive insights into these crucial processes in human infancy. In this work, we describe a systematic approach to minimise the impact of specific technical challenges inherent to acquiring MRS data in a neonatal population, including automatic segmentation, full tissue-correction and optimised GABA+ fitting and consider the minimum requirements for a robust edited-MRS acquisition. With this approach we report for the first time simultaneous GABA+, Glx (glutamate + glutamine) and GSH concentrations in the neonatal brain (n = 18) in two distinct regions (thalamus and anterior cingulate cortex (ACC)) using edited MRS at 3T.
The improved sensitivity provided by our method allows specific regional neurochemical differences to be identified including: significantly lower Glx and GSH ratios to total creatine in the thalamus compared to the ACC (p < 0.001 for both), and significantly higher GABA+ and Glx levels in the ACC following tissue-correction (p < 0.01). Furthermore, in contrast to adult GABA+ which can typically be accurately fitted with a single peak, all neonate spectra displayed a characteristic doublet GABA+ peak at 3 ppm, indicating a lower macromolecule (MM) contribution to the 3 ppm signal in neonates. Relatively high group-level variance shows the need to maximise voxel size/acquisition time in edited neonatal MRS acquisitions for robust estimation of metabolites.
Application of this method to study how these levels and balance are altered by early-life brain injury or genetic risk can provide important new knowledge about the pathophysiology underlying neurodevelopmental disorders.
•Examined effects of prenatal exposure to air pollution on neonatal brain structure.•Large study in healthy term born neonates.•Prenatal air pollution exposure was associated with altered brain ...morphology.
Prenatal exposure to air pollution is associated with adverse neurologic consequences in childhood. However, the relationship between in utero exposure to air pollution and neonatal brain development is unclear.
We modelled maternal exposure to nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10) at postcode level between date of conception to date of birth and studied the effect of prenatal air pollution exposure on neonatal brain morphology in 469 (207 male) healthy neonates, with gestational age of ≥36 weeks. Infants underwent MR neuroimaging at 3 Tesla at 41.29 (36.71–45.14) weeks post-menstrual age (PMA) as part of the developing human connectome project (dHCP). Single pollutant linear regression and canonical correlation analysis (CCA) were performed to assess the relationship between air pollution and brain morphology, adjusting for confounders and correcting for false discovery rate.
Higher exposure to PM10 and lower exposure to NO2 was strongly canonically correlated to a larger relative ventricular volume, and moderately associated with larger relative size of the cerebellum. Modest associations were detected with higher exposure to PM10 and lower exposure to NO2 and smaller relative cortical grey matter and amygdala and hippocampus, and larger relaive brainstem and extracerebral CSF volume. No associations were found with white matter or deep grey nuclei volume.
Our findings show that prenatal exposure to air pollution is associated with altered brain morphometry in the neonatal period, albeit with opposing results for NO2 and PM10. This finding provides further evidence that reducing levels of maternal exposure to particulate matter during pregnancy should be a public health priority and highlights the importance of understanding the impacts of air pollution on this critical development window.
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