Currently 7-8% of all babies born in the UK are born preterm and the incidence has increased significantly over the past two decades. Improving medical care has led to increased survival in those born prematurely; however, preterm infants carry a profound risk of severe neurological disabilities along with a spectrum of major deficits across several domains including cognition, attention, coordination and behaviour. These wide-ranging and long-term consequences represent a significant burden to health and education services, yet the aetiology of the most prevalent cognitive and behavioural disorders remain unclear.
Magnetic resonance imaging provides the means to quantitatively assess cerebral growth and development and is being increasingly employed to study the developing preterm brain. Evidence from neonatal imaging studies has revealed a number of specific cerebral alterations present in the preterm population that appear to predict neurodevelopmental outcome in early childhood and include diffuse microstructural disturbances of the developing white matter and regional volumetric tissue losses. In addition, a number of perinatal risk factors have been identified that are associated with both preterm birth and altered cerebral development.
This thesis aims to test the hypothesis that connectivity and growth of developing neural systems are adversely affected by prematurity at birth and additionally influenced by specific perinatal risk factors. This is achieved through the application of multi-subject, multi-modal MRI analysis to quantify tissue microstructure and volume alongside novel methods for defining regional connectivity in the developing preterm brain.
Evidence is provided that suggests connected neural structures are disturbed in preterm infants resulting in a complex pattern of regional micro- and macrostructural alteration that is evident at term-equivalent age and potentiated by respiratory morbidity. This is convergent with current theories of the mechanisms underpinning preterm brain injury and provides further insight into the consequences of preterm birth on brain development.