Fixel-based analysis reveals alterations is brain microstructure and macrostructure of preterm-born infants at term equivalent age

Preterm birth causes significant disruption in ongoing brain development, frequently resulting in adverse neurodevelopmental outcomes. Brain imaging using diffusion MRI may provide valuable insight into microstructural properties of the developing brain. The aim of this study was to establish whether the recently introduced fixel-based analysis method, with its associated measures of fibre density (FD), fibre bundle crosssection (FC), and fibre density and bundle cross-section (FDC), is suitable for the investigation of the preterm infant brain at term equivalent age. High-angular resolution diffusion weighted images (HARDI) of 55 preterm-born infants and 20 term-born infants, scanned around term-equivalent age, were included in this study (3 T, 64 directions, b= 2000 s/mm(2)). Postmenstrual age at the time of MRI, and intracranial volume (FC and FDC only), were identified as confounding variables. Gestational age at birth was correlated with all fixel measures in the splenium of the corpus callosum. Compared to term-born infants, preterm infants showed reduced FD, FC, and FDC in a number of regions, including the corpus callosum, anterior commissure, cortico-spinal tract, optic radiations, and cingulum. Preterm infants with minimal macroscopic brain abnormality showed more extensive reductions than preterm infants without any macroscopic brain abnormality; however, little differences were observed between preterm infants with no and with minimal brain abnormality. FC showed significant reductions in preterm versus term infants outside regions identified with FD and FDC, highlighting the complementary role of these measures. Fixel-based analysis identified both microstructural and macrostructural abnormalities in preterm born infants, providing a more complete picture of early brain development than previous diffusion tensor imaging (DTI) based approaches.