Synopsis

Objectives

• This talk will focus on brain development in infants born preterm
• Discuss differences in diffusion MRI measures in white- and grey-matter between preterm infants compared to term controls
• Assess relationship between dMRI measures and relevant perinatal clinical factors
• Discuss relationship between dMRI measures at term equivalent age and subsequent neurodevelopmental outcome

Background

Summary of Recent Studies

White matter development

Using high angular resolution multi-shell dMRI to assess connectivity between brain regions and connectivity metrics obtained from the diffusion tensor (fractional anisotropy, FA) and NODDI model characteristics (neurite density index, NDI), we assessed regional differences in brain maturation from 25 weeks gestation to term equivalent age.¹⁰ Brain development prior to term equivalent age is characterised by an increase in FA and NDI. Connections to and from deep grey matter showed most rapid developmental changes during this period while intra-frontal, frontal to cingulate, frontal to caudate and inter-hemispheric connections matured more slowly. This maturational gradient is consistent with the regional heterogeneity observed histologically with myelination progressing from inferior to superior and from posterior to anterior.^11,12

Relationship with Perinatal Risk Factors

The preterm brain is susceptible to injury from ischaemic, haemorrhagic, inflammatory and infective insult: immature oligodendrocytes are particularly sensitive to injury, as are subplate neurons which form synapses with thalamo-cortical afferents in the transient subplate layer that are essential for normal cortical development. These vulnerabilities may help explain the abnormalities in brain growth and development observed using quantitative MR imaging in infants and children who were born preterm. We assessed the relationship between perinatal risk factors and white matter development in a large group of preterm infants (n = 491) at term equivalent age.¹³ Risk factors for diffuse white matter injury were lower GA at birth (Figure 1), fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition, necrotizing enterocolitis and male sex. Exposure to multiple risk factors exacerbated white matter injury, supporting the multiple hit hypothesis for the variation in brain development observed following preterm birth.

Development of the Cerebral Cortex

In addition to studying white matter, cortical maturation can be assessed using dMRI. Prior to 32 weeks gestation age, the cortex is dominated by perpendicular radial glia and apical dendrites, resulting in nonzero anisotropy,¹⁴ and is accompanied by decreases in both mean diffusivity and FA due to increasing cellular density, complexity, neurite overgrowth, and maturing dendritic cytoarchitecture.^14-15 Cortical FA declines up to around 38 weeks gestational age, with higher initial values and rate of change in the frontal and temporal poles, and parietal cortex, and lower initial values in the perirolandic, and medial occipital cortices, suggesting that elongation and branching of dendrites orthogonal to cortical columns occurs later in the association cortex (Figure 2).¹⁵ Cortical development, as assessed by d-MRI, is impaired in preterm infants who have slower postnatal growth.¹⁶ Moreover, the rate of microstructural maturation correlates not only with local cortical growth but also importantly with neurodevelopmental performance at 2 years of age.¹⁵

Conclusion

Acknowledgements

References

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