Abstract
The aim of this study is to examine whether advanced magnetic resonance imaging (MRI) techniques can detect early brain injury caused by intrauterine inflammation and inappropriate initial respiratory support in preterm lambs. Neuropathology caused by intrauterine inflammation is exacerbated by mechanical ventilation at birth and is detectable with advanced MRI techniques. Pregnant ewes received intra-amniotic lipopolysaccharide (LPS) 7 days prior to delivery at ~125 days of gestation (85% of gestation), whereupon lambs were delivered and randomised to receive an injurious (LPS + INJ, n = 6) or protective (LPS + PROT, n = 6) ventilation strategy. MRI of the brain was conducted 90 min after preterm delivery, using structural, diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) techniques. A colour map threshold technique was utilised to compare distributions of low diffusivity voxels in the brains of LPS-exposed lambs with those not exposed to LPS (PROT, n = 7 PROT and INJ, n = 10). No overt cerebral injury was identified on structural MRI images of any lamb. However, on DTI, axial diffusivity, radial diffusivity, and mean diffusivity values were lower and significantly more heterogeneous in specific brain regions of lambs in the LPS + INJ group compared to the LPS + PROT group. Colour mapping revealed lower diffusivity in the thalamus, periventricular white matter, internal capsule, and frontal white matter in the LPS + INJ group compared to LPS + PROT group. The MRS peak area ratios of lactate, relative to those for the metabolites creatine, choline, and N-acetylaspartate, were not different between LPS-exposed groups. Lambs exposed to LPS had lower diffusivity within the white matter regions assessed than non-LPS-treated control lambs. DTI colour map threshold techniques detected early brain injury in preterm lambs exposed to intrauterine inflammation and detected differences between injurious and protective ventilation strategies. DTI mapping approaches are potentially useful for early detection of subtle brain injury in premature infants.
Highlights
Infants born preterm are at a high risk of brain injury, with the rate of neurodevelopmental disability exceeding 50%, and cerebral palsy rates at ~10% [1, 2]
There were frequently lower axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) intensities in the Th, internal capsule (IC), periventricular white matter (PVWM), and frontal white matter (FWM) in a subgroup of LPS + INJ lambs compared to LPS + PROT, as well as when compared to controls when compared to controls that were not exposed to LPS
We aimed to detect subtle brain injury in lambs associated with intrauterine inflammation and different ventilation strategies within the first 90 min after birth, using clinical 3T magnetic resonance imaging (MRI)
Summary
Infants born preterm are at a high risk of brain injury, with the rate of neurodevelopmental disability exceeding 50%, and cerebral palsy rates at ~10% [1, 2]. A protective ventilation strategy did not reduce the severity of brain injury, assessed histologically, after IA LPS [12] compared to control lambs [5]. These results support clinical findings that intrauterine inflammation increases the risk and severity of postnatal white matter injury [13], periventricular leukomalacia, and periventricular/intraventricular haemorrhages [14,15,16,17]. Preterm infants exposed to chorioamnionitis are at a high risk of long-term neurodevelopmental impairment including cerebral palsy [13, 18, 19]
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