Date of Award

January 2024

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)



First Advisor

Seyedmehdi Payabvash


Rapid changes in diffusion properties and white matter microstructural integrity in neonatal brains complicates the interpretation of advanced MRI techniques such as diffusion weighted (DWI) and diffusion tensor imaging (DTI). Thus, the goal of this work is to characterize age-related normative diffusion patterns in neonates and determine the impacts of postnatal growth trajectory, delivery method, and hypoxic ischemia on neonatal brain diffusion metrics. From a large cohort of neonates who had received brain MRI within 3 months of birth between January 2013 and March 2021, the following cohorts were identified for individual analyses: a cohort of neonates with no neurological abnormality identified on DWI or DTI series, a cohort of very preterm neonates with information in the health record to obtain postnatal weight measurements, a cohort of preterm neonates with information in the health record to obtain delivery method and postnatal complication information, and a cohort of term neonates who had clinical and radiological evidence of hypoxic ischemic encephalopathy. Using both tract based spatial statistics and voxel-wise general linear models, the following were investigated: age-related normative diffusion patterns in neonates, the relationship between postnatal weight gain and brain white matter maturation in very preterm neonates, the relationship between delivery method and brain white matter maturation in preterm neonates, and the relationship between hypoxic ischemic encephalopathy (HIE) severity and ischemic lesion location in term neonates. All analyses were confirmed by utilizing a white matter atlas generated by Johns Hopkins University to conduct white matter tract specific linear regression analyses. Diffuse reduction in apparent diffusivity coefficient (ADC) values was observed across normative neonatal brain with increasing gestational age at time of scan. The highest rates of decline in normative ADC values correlated topographically with the highest rates of increase in normative fractional anisotropy (FA) values and rates of decline in normative mean diffusivity (MD) values. Gestational age at birth was also found to be independently associated with normative diffusion metrics in regions such as the convexity cortex and corpus callosum. An online, interactive, age-adjusted atlas displaying normative changes in ADC, FA, and MD values with increasing gestational age was created and is available for public use. In very preterm neonates, both birth weight and postnatal weight gain were found to be independently associated with DTI metrics of improved white matter development in the corpus callosum and sagittal striatum. In preterm neonates, DTI metrics indicative of reduced WM development were observed in the corpus callosum, internal capsule, and corona radiata of neonates delivered by C-section compared to those delivered vaginally after adjusted for numerous demographic variables and perinatal occurrences as covariates. In term neonates with HIE, mild and moderated HIE was found to be primarily distributed across arterial supply territory border zones and deep and subcortical white matter while severe HIE involved deep grey matter nuceli and the hippocampus. The results presented here may aid the quantitative assessment of DWI and DTI scans for the identification of developmental and pathological abnormalities by providing a reference of normative diffusion metrics in the postnatal period. Furthermore, WM developmental delay in specific brain regions was found to be independently associated with risk factors such as low birth weight, postnatal growth delay, and C-section delivery. These deviations from normative patterns may serve as biomarkers to help identify neonates that may benefit from close neurological follow up to mitigate adverse long term neurological deficits. Lastly, knowledge of the topographical distribution of ischemic lesions with HIE severity may further aid the application of the normative diffusion metric atlas in the identification of subtle ischemic injury.


This is an Open Access Thesis.

Open Access

This Article is Open Access