Abstract
Background and AimHigh tidal volume (VT) ventilation during resuscitation of preterm lambs results in brain injury evident histologically within hours after birth. We aimed to investigate whether magnetic resonance spectroscopy (MRS) and/or diffusion tensor imaging (DTI) can be used for early in vivo detection of ventilation-induced brain injury in preterm lambs.MethodsNewborn lambs (0.85 gestation) were stabilized with a “protective ventilation” strategy (PROT, n = 7: prophylactic Curosurf, sustained inflation, VT 7 mL/kg, positive end expiratory pressure (PEEP) 5 cmH2O) or an initial 15 minutes of “injurious ventilation” (INJ, n = 10: VT 12 mL/kg, no PEEP, late Curosurf) followed by PROT ventilation for the remainder of the experiment. At 1 hour, lambs underwent structural magnetic resonance imaging (Siemens, 3 Tesla). For measures of mean/axial/radial diffusivity (MD, AD, RD) and fractional anisotropy (FA), 30 direction DTI was performed. Regions of interests encompassed the thalamus, internal capsule, periventricular white matter and the cerebellar vermis. MRS was performed using a localized single-voxel (15×15×20 mm3, echo time 270 ms) encompassing suptratentorial deep nuclear grey matter and central white matter. Peak-area ratios for lactate (Lac) relative to N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) were calculated. Groups were compared using 2-way RM-ANOVA, Mann-Whitney U-test and Spearman's correlations.ResultsNo cerebral injury was seen on structural MR images. Lambs in the INJ group had higher mean FA and lower mean RD in the thalamus compared to PROT lambs, but not in the other regions of interest. Peak-area lactate ratios >1.0 was only seen in INJ lambs. A trend of higher mean peak-area ratios for Lac/Cr and Lac/Cho was seen, which correlated with lower pH in both groups.ConclusionAcute changes in brain diffusion measures and metabolite peak-area ratios were observed after injurious ventilation. Early MRS/DTI is able to detect the initiation of ventilation-induced brain injury.
Highlights
Preterm infants are at high risk of brain injury and long-term neurodevelopmental impairments [1,2,3]
Schmolzer et al [6] demonstrated that the discrepancy between the estimated tidal volumes (VT) during mask-ventilation, and the actual measured VT delivered to the baby, can be substantial, with many infants receiving excessive VT
The PROT strategy consisted of intubation, administration of intratracheal surfactant (Curosurf 100 mg/kg) and one sustained inflation for 30 seconds at peak inflation pressure (PIP) 35 cmH2O delivered with a Neopuff (Fisher & Paykel Healthcare, Panmure, Auckland, New Zealand)
Summary
Preterm infants are at high risk of brain injury and long-term neurodevelopmental impairments [1,2,3]. Infants born preterm often receive respiratory support at birth, and may be exposed to unintentional injurious ventilation in the delivery room. High VT ventilation causes cerebral blood flow instability, white matter injury, inflammation, vascular leakage and oxidative stress, evident as early as 90 minutes after birth. It is not possible to detect brain injury histologically in survivors of preterm birth; instead, magnetic resonance imaging (MRI) provides a potential biomarker for acute brain injury in preterm newborns [9,10,11,12]. High tidal volume (VT) ventilation during resuscitation of preterm lambs results in brain injury evident histologically within hours after birth. We aimed to investigate whether magnetic resonance spectroscopy (MRS) and/or diffusion tensor imaging (DTI) can be used for early in vivo detection of ventilation-induced brain injury in preterm lambs
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