Irzan, Hassna; (2022) Neuroimaging characterisation of the extreme preterm phenotype at adolescence. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The preterm phenotype results from the interplay of multiple disorders that encompass brain abnormalities and poor cognitive outcomes. The global increase in premature birth rate is of great concern since the number of subjects with a broad spectrum of neurologic and cognitive disorders is increasing with associated costs for society, health care, and education systems. Better socioeconomic factors and improved neonatal care have strengthened the ability to treat babies born at immature gestational ages. However, increased survival rates have not paired with an equal decrease in neonatal morbidity. Neuroimaging studies have focused on preterm neonates and revealed that, compared with their term-born peers, these subjects are at higher risk of brain abnormalities and adverse cognitive outcomes; however, very few studies have investigated the development trajectory into adolescence and adulthood, especially in extreme preterm birth. Therefore, this work is motivated by the lack of a comprehensive understanding of the long-term effects of preterm birth. This dissertation leverages the availability of neuropsychological and multi-contrast neuroimaging data of extremely preterm born young adults to analyse the preterm phenotype and develop new methodologies to detect biomarkers of prematurity. Specifically, the thesis performs an extensive White Matter (WM) analysis by combining state-of-the-art models for the estimation of WM structure and microstructure; it conducts a comprehensive resting-state fMRI analysis, and proposes novel machine learning frameworks to establish associations between neuroimaging measurements and cognitive performance. The findings show significant changes of WM connectivity at both the structural and microstructural levels; the alterations are found overall in the brain and even more marked in the deep grey matter region and the sensorimotor areas. Comparable results from functional connectivity provide further evidence that brain abnormalities associated with premature exposure to the extrauterine environment are present not only at term equivalent age but also persist into early adulthood. This work may give new insights to characterise the preterm phenotype and identify new biomarkers of prematurity. This would predict the long-term effect of prematurity on the brain and inform personalised treatments and targeted therapies at an early stage.

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