Proper timing for the evaluation of neonatal brain white matter development: a diffusion tensor imaging study

Objective: We aimed to determine the timing for assessing birth status of the developing brain (i.e. brain maturity at birth) by exploring the postnatal age-related changes in neonatal brain white matter (WM). Methods: The institutional review board approved this study and all informed parental consents were obtained. 133 neonates (gestational age, 30–42 weeks) without abnormalities on MRI were studied with regard to WM development by diffusion tensor imaging-derived fractional anisotropy (FA). Tract-based spatial statistics (TBSS), locally-weighted scatterplot smoothing (LOESS) and piecewise linear-fitting were used to investigate the relationship between FA and postnatal age. FA along corticospinal tract (CST), optic radiation (OR), auditory radiation (AR) and thalamus-primary somatosensory cortex (thal-PSC) were extracted by automated fibre-tract quantification; their differences and associations with neonatal neurobehavioural scores at various postnatal age ranges were analysed by Wilcoxon’s rank-sum test and Pearson’s correlation. Results: Using TBSS, postnatal age (days 1–28) positively correlated with FA in multiple WMs, including CST, OR, AR and thal-PSC (p<0.05). On the other hand, when narrowing the postnatal age window to days 1–14, no significant correlation was found, suggesting a biphasic WM development. LOESS and piecewise linear-fitting indicated that FA increased mildly before day 14 and its growth accelerated thereafter. Both FA and correlations with neurobehavioural scores in postnatal age range 2 (days 15–28) were significantly higher than in range 1 (days 1–14) (FA comparison: p<0.05; maximal correlation-coefficient: 0.693 vs. 0.169). Conclusion: Brain WM development during the neonatal stage includes two phases, i.e. a close-to-birth period within the first 14 days and a following accelerated maturation period. Therefore, evaluations of birth status should preferably be performed during the first period. Key Points: • Brain white matter development within the first two postnatal weeks resembles a close-to-birth maturation. • Brain white matter development in the audio-visual, sensorimotor regions accelerates after two postnatal weeks. • Postnatal age-related effects should be considered in comparing preterm and term neonates.