Sex Effects on Brain Maturation in Former Extremely Preterm Neonates – A Quantitative MRI Study

Introduction and aim: Diffusion tensor-derived metrics [fractional anisotropy (FA); apparent diffusion coefficient (ADC)] and tissue-specific relaxation properties [T1-relaxation time (T1R); T2-relaxation time (T2R)] allow for a quantitative assessment of brain maturation. The aim of this study was to investigate sex-related maturity differences of infratentorial/supratentorial regions in former extremely preterm infants by means of a quantitative MR approach.

Method: Quantitative MRI sequence acquisitions (1.5 Tesla) were analyzed in a sample of 35 extremely preterm neonates [< 28 weeks gestational age (GA)] (female: n = 17; male: n = 18) imaged at term-equivalent ages. FA/ADC and T1R/T2R of the midbrain and the right/left posterior limb of the internal capsule (PLIC) were determined on DTI- and multi-dynamic multi-echo (MDME) sequence-based imaging data. ANCOVA (covariate: GA at MRI) was used for group comparison. A paired t-test was used to compare the left and right PLIC in both female and male neonates.

Result: Significant differences were observed in T1R of the midbrain between female and male infants (p = .02). In both sexes, FA [p(♀)=.002/p(♂)=.002], ADC [p(♀)=.02/p(♂)=.008], and T1R [p(♀)<.001/p(♂)=.008] differed significantly between the right and left PLIC.

Conclusion: Although the myelination sequence of the PLIC appears to follow quite a similar pattern in both sexes, characterized by more advanced white matter myelination in left-hemispheric internal capsule regions, the midbrain of male preterms is more immature compared to female infants at term-equivalent ages. Relaxometry- and DTI-based mapping approaches provide sensitive biomarkers for the detection of sex-related and interhemispheric differences of white matter maturity at an early stage of cerebral development. Sex effects on brain maturation need further attention for the personalization of pediatric neuroimaging.

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Publication History

Article published online:
19 August 2021