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Diffusion Tensor Imaging analysed by Tract-Based Spatial Statistics as a biomarker of adverse outcome after hypoxic-ischaemic encephalopathy treated with hypothermia

Presented at the Neonatal Society 2011 Spring Meeting.

Tusor N, Smee N, Arichi T, Counsell S, Azzopardi D, Cowan F, Edwards AD

Centre For the Developing Brain, MRC Clinical Sciences Centre and Institute of Clinical Sciences, Hammersmith Campus, Imperial College, London

Background: Despite the success of hypothermic neural rescue, hypoxic-ischaemic encephalopathy (HIE) remains a major cause of neonatal morbidity and mortality. Progress in neuroprotection now requires qualified biomarkers which detect increased therapeutic effects from additional treatments in phase 2 studies. Diffusion Tensor Imaging (DTI) analysed by Tract-Based Spatial Statistics (TBSS) detects the therapeutic effect of hypothermia (1), and this study aimed to determine whether TBSS might provide a biomarker of adverse outcome in small groups of patients who are cooled.

Methods: We examined DTI data obtained in 38 term infants [gestational age median, (range): 39.5, (36.1-42.4)] with HIE [10 min Apgar median (range): 5, (0-9); lowest pH within 1 hour after birth median (range): 6.8, (6.4-7.1)] who underwent therapeutic hypothermia for 72 hours. On each infant single shot echo planar DTI was acquired in 32 non-collinear directions on a Philips 3T system. The median age at scan was day 7, (range: 3-14 days) and the scans were performed under sedation with oral chloral-hydrate (30-50mg/kg). Following pre-processing by brain extraction, eddy current correction and generation of fractional anisotropy (FA) maps, voxel-wise statistical analysis was carried out using TBSS. Infants were assessed using the Griffith Developmental Scales (Revised) and segregated into 2 groups: 1. Developmental Quotient (DQ) ≥ 75 or 2. DQ ≤ 75 or death. 

Results: Neurodevelopmental assessments were performed at median age of 16 months (range: 6-28). 26 infants were classed in group 1; and 12 in group 2, of whom 8 died. Group 2 had significantly lower FA values in the left anterior limb of the internal capsule, in the posterior limbs of the internal capsule bilaterally and in the left optic radiation (p<0.05) following correction for multiple comparisons and age at scan, as shown in the figure.

Diffusion Tensor Imaging analysed by Tract-Based Spatial Statistics as a biomarker of adverse outcome after hypoxic-ischaemic encephalopathy treated with hypothermia


Figure: Axial images of white matter tracts of all subjects. The
group FA skeleton is shown in red. Voxels showing lower FA in
infants with adverse outcome are shown in blue.

Conclusion: DTI analysed by TBSS shows reduced FA in infants with adverse outcome after therapeutic hypothermia for HIE, and may be a useful biomarker in infants treated with hypothermic neural rescue therapy.

Corresponding author: nora.tusor@imperial.ac.uk

References
1. Porter et al. Tract-based spatial statistics of magnetic resonance images to assess disease treatment effects in perinatal asphyxia encephalopathy. Peditaric Res. 2010:68(3):205-9.

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