Diffusion Weighted Magnetic Resonance Imaging of in utero and ex utero Human Brain Development

Abstract

The primary objective of this thesis was to establish quantitative measurements of normal fetal brain tissue across gestation using diffusion magnetic resonance imaging (MRI); the secondary aim was to compare diffusion metrics in fetuses with normal brain development to those with isolated ventriculomegaly (VM), congenital heart disease and in infants born preterm. Fetal diffusion weighted imaging (DWI) was optimised, and a motion-corrected diffusion tensor imaging (DTI) technique was utilized to produce apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values across gestation in normal fetal cohorts. Tract-based spatial statistics (TBSS) was utilised to analyse DTI in neonates with isolated VM compared to controls. Diffusion and volumetric MR data in preterm infants were analysed using an objective segmentation approach to characterise ex utero neurodevelopment, and to establish the effects of perinatal clinical factors on brain development. Normative ADC values were established in the fetal brain (n=52) across a large gestational age range. Increased ADC values were found in fetuses (n=24) and neonates (n=22) with isolated VM compared to controls; decreased FA was also demonstrated in neonates with VM. In preterm neonates (n=208), white and deep grey matter exhibited significantly increasing FA, and decreasing ADC, axial and radial diffusivity measures with increasing age at scan. DTI measures in the cortex significantly decreased with increasing age at scan; volume measures increased in all brain regions. Clinical factors including respiratory support and age at birth affected regional DTI and volumetric measures in preterm infants. FA values from a normal fetal cohort using motion-corrected DTI (n=26) were compared to preterm neonates (n=32) and significant differences were found. This thesis produced normal fetal diffusion data comparable to that produced in neonates. Quantifiable MR techniques can be used to explore the relationship between in utero and ex utero brain development and study alterations of normal fetal maturation.