White matter integrity at school age in children from the drift randomised controlled trial of neonatal post haemorrhagic ventricular dilatation

Presented at the Neonatal Society Spring Meeting 2019.

Authors: Crowell, J.¹, Thai, N. J.^1,2, Smith-Collins, A.^1,3_, Jary, S.¹, Whitelaw, A.¹  &  Luyt, K.^1,3

Institution(s)
¹University of Bristol, Bristol, ²CRICBristol, ³St. Michael’s Hospital UHBristol NHS Trust. 

Introduction
Drainage, Irrigation, and Fibrinolytic Therapy (DRIFT) was developed to improve the neurodevelopmental outcomes of preterm infants with Intraventricular Haemorrhage (IVH) and post-haemorrhagic ventricular dilatation (PHVD), a complication which causes significant neurodisability in survivors. Our aim was to identify and characterise white matter asymmetries between patients given DRIFT treatment compared to those with standard treatment using Tract Based Spatial Statistics (TBSS) on Diffusion Tensor Imaging (DTI) data and brain volume differences in grey and white matter from high resolution MRI scans performed at 10-year follow-up.

Methods
TBSS voxelwise statistical comparison of fractional anisotropy (FA) was used to compare mean regional FA and left-right hemispheric asymmetries between the two treatment groups. Two-sample t-tests were performed for groupwise contrasts with statistical significance set at p<0.05, corrected for multiple comparisons. To examine differences in grey and white matter tissue volumes, Voxel Based Morphometry (VBM) was performed and Two-sample t-tests utilised to compare treatment groups. Of the patients scanned at 10 years post treatment (n=28), 22 were able to complete the Diffusion Tensor Imaging (DTI) sequence. Standard Treatment Group n=9, DRIFT Treatment Group n=13.

Results
TBSS symmetry analysis L>R showed the DRIFT treatment group to have statistically significant differences in homotopic white matter tracts across hemispheres compared to the Standard treatment group. Tracts showing greater symmetry in the DRIFT vs Standard treatment groups included the anterior thalamic radiation, forceps minor, superior and inferior longitudinal fasiculus and corticospinal tract (all p<0.05 corrected). No significant differences in volume were found in the VBM analysis in either white or grey matter tissue between the two treatment groups at p<0.05 corrected.

Conclusions
The significant hemisphere asymmetries between groups suggest that in specific white matter tracts the DRIFT treatment group has better hemispheric symmetry in white matter connectivity compared to the standard treatment group (Smith et al 2007). Further research is needed to fully understand the implications of regional white matter asymmetries between treatment groups and whether this relates to functional outcomes.
Further research is needed to fully understand the implications of regional white matter asymmetries between treatment groups.

References
Smith et al. Acquisition and voxelwise analysis of multi-subject diffusion data with tract-based spatial statistics. Nat Protoc. 2007;2(3):499-503.
This project was funded by the National Institute for Health Research HTA 12/35/61. NHS Research Ethics approval was granted.

Senior author supporting presentation on day of meeting: Dr K. Luyt

Corresponding author e-mail address: JC17467@bristol.ac.uk