Brain tissue microstructural and free-water composition 13 years after very preterm birth
Claire Kelly,
Thijs Dhollander,
Ian H Harding,
Wasim Khan,
Richard Beare,
Jeanie LY Cheong,
Lex W Doyle,
Marc Seal,
Deanne K Thompson,
Terrie E Inder,
Peter J Anderson
Affiliations
Claire Kelly
Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Melbourne, Australia; Victorian Infant Brain Studies (VIBeS), Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Australia; Developmental Imaging, Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Australia; Corresponding author: Claire Kelly, Turner Institute for Brain and Mental Health, School of Psychological Sciences, 18 Innovation Walk, Monash University, Clayton, VIC, 3800, Australia
Thijs Dhollander
Developmental Imaging, Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Australia
Ian H Harding
Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Monash Biomedical Imaging, Monash University, Melbourne, Australia
Wasim Khan
Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia
Richard Beare
Developmental Imaging, Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Australia
Jeanie LY Cheong
Victorian Infant Brain Studies (VIBeS), Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Australia; The Royal Women's Hospital, Melbourne, Australia; Department of Obstetrics and Gynaecology, The University of Melbourne, Melbourne, Australia
Lex W Doyle
Victorian Infant Brain Studies (VIBeS), Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Australia; The Royal Women's Hospital, Melbourne, Australia; Department of Obstetrics and Gynaecology, The University of Melbourne, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia
Marc Seal
Developmental Imaging, Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia
Deanne K Thompson
Victorian Infant Brain Studies (VIBeS), Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Australia; Developmental Imaging, Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia
Terrie E Inder
Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Peter J Anderson
Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Melbourne, Australia; Victorian Infant Brain Studies (VIBeS), Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Australia
There have been many studies demonstrating children born very preterm exhibit brain white matter microstructural alterations, which have been related to neurodevelopmental difficulties. These prior studies have often been based on diffusion MRI modelling and analysis techniques, which commonly focussed on white matter microstructural properties in children born very preterm. However, there have been relatively fewer studies investigating the free-water content of the white matter, and also the microstructure and free-water content of the cortical grey matter, in children born very preterm. These biophysical properties of the brain change rapidly during fetal and neonatal brain development, and therefore such properties are likely also adversely affected by very preterm birth. In this study, we investigated the relationship of very preterm birth (<30 weeks’ gestation) to both white matter and cortical grey matter microstructure and free-water content in childhood using advanced diffusion MRI analyses. A total of 130 very preterm participants and 45 full-term control participants underwent diffusion MRI at age 13 years. Diffusion tissue signal fractions derived by Single-Shell 3-Tissue Constrained Spherical Deconvolution were used to investigate brain tissue microstructural and free-water composition. The tissue microstructural and free-water composition metrics were analysed using a voxel-based analysis and cortical region-of-interest analysis approach. Very preterm 13-year-olds exhibited reduced white matter microstructural density and increased free-water content across widespread regions of the white matter compared with controls. Additionally, very preterm 13-year-olds exhibited reduced microstructural density and increased free-water content in specific temporal, frontal, occipital and cingulate cortical regions. These brain tissue composition alterations were strongly associated with cerebral white matter abnormalities identified in the neonatal period, and concurrent adverse cognitive and motor outcomes in very preterm children. The findings demonstrate brain microstructural and free-water alterations up to thirteen years from neonatal brain abnormalities in very preterm children that relate to adverse neurodevelopmental outcomes.
