Dataset Information

Diffusion Tensor Imaging Colour Mapping Threshold for Identification of Ventilation-Induced Brain Injury after Intrauterine Inflammation in Preterm Lambs.

ABSTRACT:

Purpose

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.

Hypothesis

Neuropathology caused by intrauterine inflammation is exacerbated by mechanical ventilation at birth and is detectable with advanced MRI techniques.

Methods

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).

Results

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.

Conclusion

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.

SUBMITTER: Alahmari DM

PROVIDER: S-EPMC5380678 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Diffusion Tensor Imaging Colour Mapping Threshold for Identification of Ventilation-Induced Brain Injury after Intrauterine Inflammation in Preterm Lambs.

Alahmari Dhafer M DM Skiöld Beatrice B Barton Samantha K SK Nitsos Ilias I McDonald Courtney C Miller Suzanne L SL Zahra Valerie V Galinsky Robert R Wu Qizhu Q Farrell Michael John MJ Moss Timothy J TJ Hooper Stuart B SB Pearson James T JT Polglase Graeme R GR

Frontiers in pediatrics 20170405

<h4>Purpose</h4>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.<h4>Hypothesis</h4>Neuropathology caused by intrauterine inflammation is exacerbated by mechanical ventilation at birth and is detectable with advanced MRI techniques.<h4>Methods</h4>Pregnant ewes received intra-amniotic lipopolysaccharide (LPS) 7 days prior ...[more]

PMID: 28424764

Similar Datasets

Project description:PurposeInjurious mechanical ventilation causes white matter (WM) injury in preterm infants through inflammatory and haemodynamic pathways. The relative contribution of each of these pathways is not known. We hypothesised that in vivo magnetic resonance imaging (MRI) can detect WM brain injury resulting from mechanical ventilation 24 h after preterm delivery. Further we hypothesised that the combination of inflammatory and haemodynamic pathways, induced by umbilical cord occlusion (UCO) increases brain injury at 24 h.MethodsFetuses at 124±2 days gestation were exposed, instrumented and either ventilated for 15 min using a high tidal-volume (VT) injurious strategy with the umbilical cord intact (INJ; inflammatory pathway only), or occluded (INJ+UCO; inflammatory and haemodynamic pathway). The ventilation groups were compared to lambs that underwent surgery but were not ventilated (Sham), and lambs that did not undergo surgery (unoperated control; Cont). Fetuses were placed back in utero after the 15 min intervention and ewes recovered. Twenty-four hours later, lambs were delivered, placed on a protective ventilation strategy, and underwent MRI of the brain using structural, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) techniques.ResultsAbsolute MRS concentrations of creatine and choline were significantly decreased in INJ+UCO compared to Cont lambs (P = 0.03, P = 0.009, respectively); no significant differences were detected between the INJ or Sham groups and the Cont group. Axial diffusivities in the internal capsule and frontal WM were lower in INJ and INJ+UCO compared to Cont lambs (P = 0.05, P = 0.04, respectively). Lambs in the INJ and INJ+UCO groups had lower mean diffusivities in the frontal WM compared to Cont group (P = 0.04). DTI colour mapping revealed lower diffusivity in specific WM regions in the Sham, INJ, and INJ+UCO groups compared to the Cont group, but the differences did not reach significance. INJ+UCO lambs more likely to exhibit lower WM diffusivity than INJ lambs.ConclusionsTwenty-four hours after injurious ventilation, DTI and MRS showed increased brain injury in the injuriously ventilated lambs compared to controls. DTI colour mapping threshold approach provides evidence that the haemodynamic and inflammatory pathways have additive effects on the progression of brain injury compared to the inflammatory pathway alone.

Project description:BackgroundAntenatal conditions that are linked with preterm birth, such as intrauterine inflammation, can influence fetal cardiac development thereby rendering the heart more vulnerable to the effects of prematurity. We aimed to investigate the effect of intrauterine inflammation, consequent to lipopolysaccharide exposure, on postnatal cardiac growth and maturation in preterm lambs.MethodsPreterm lambs (~129 days gestational age) exposed antenatally to lipopolysaccharide or saline were managed according to contemporary neonatal care and studied at postnatal day 7. Age-matched fetal controls were studied at ~136 days gestational age. Cardiac tissue was sampled for molecular analyses and assessment of cardiac structure and cardiomyocyte maturation.ResultsLambs delivered preterm showed distinct ventricular differences in cardiomyocyte growth and maturation trajectories as well as remodeling of the left ventricular myocardium compared to fetal controls. Antenatal exposure to lipopolysaccharide resulted in further collagen deposition in the left ventricle and a greater presence of immune cells in the preterm heart.ConclusionsAdverse impacts of preterm birth on cardiac structure and cardiomyocyte growth kinetics within the first week of postnatal life are exacerbated by intrauterine inflammation. The maladaptive remodeling of the cardiac structure and perturbed cardiomyocyte growth likely contribute to the increased vulnerability to cardiac dysfunction following preterm birth.ImpactPreterm birth induces maladaptive cardiac remodeling and adversely impacts cardiomyocyte growth kinetics within the first week of life in sheep. These effects of prematurity on the heart are exacerbated when preterm birth is preceded by exposure to intrauterine inflammation, a common antecedent of preterm birth. Inflammatory injury to the fetal heart coupled with preterm birth consequently alters neonatal cardiac growth and maturation and thus, may potentially influence long-term cardiac function and health.

Project description:Preterm infants often require mechanical ventilation due to lung immaturity including reduced or abnormal surfactant. Since cyclic stretch with cycle-by-cycle variability is known to augment surfactant release by epithelial cells, we hypothesized that such in vivo mechanotransduction improves surfactant maturation and hence lung physiology in preterm subjects. We thus tested whether breath-by-breath variability in tidal volume (VT) in variable ventilation (VV) can be tuned for optimal performance in a preterm lamb model. Preterm lambs were ventilated for 3 h with conventional ventilation (CV) or two variants of VV that used a maximum VT of 1.5 (VV1) or 2.25 (VV2) times the mean VT. VT was adjusted during ventilation to a permissive pCO2 target range. Respiratory mechanics were monitored continuously using the forced oscillation technique, followed by postmortem bronchoalveolar lavage and tissue collection. Both VVs outperformed CV in blood gas parameters (pH, SaO2, cerebral O2 saturation). However, only VV2 lowered PaCO2 and had a higher specific respiratory compliance than CV. VV2 also increased surfactant protein (SP)-B release compared to VV1 and stimulated its production compared to CV. The production and release of proSP-C however, was increased with CV compared to both VVs. There was more SP-A in both VVs than CV in the lung, but VV2 downregulated SP-A in the lavage, whereas SP-D significantly increased in CV in both the lavage and lung. Compared to CV, the cytokines IL-1β, and TNFα decreased with both VVs with less inflammation during VV2. Additionally, VV2 lungs showed the most homogeneous alveolar structure and least inflammatory cell infiltration assessed by histology. CV lungs exhibited over-distension mixed with collapsed and interstitial edematous regions with occasional hemorrhage. Following VV1, some lambs had normal alveolar structure while others were similar to CV. The IgG serum proteins in the lavage, a marker of leakage, were the highest in CV. An overall combined index of performance that included physiological, biochemical and histological markers was the best in VV2 followed by VV1. Thus, VV2 outperformed VV1 by enhancing SP-B metabolism resulting in open alveolar airspaces, less leakage and inflammation and hence better respiratory mechanics.

Project description:BackgroundThe onset of mechanical ventilation is a critical time for the initiation of cerebral white matter (WM) injury in preterm neonates, particularly if they are inadvertently exposed to high tidal volumes (VT) in the delivery room. Protective ventilation strategies at birth reduce ventilation-induced lung and brain inflammation and injury, however its efficacy in a compromised newborn is not known. Chorioamnionitis is a common antecedent of preterm birth, and increases the risk and severity of WM injury. We investigated the effects of high VT ventilation, after chorioamnionitis, on preterm lung and WM inflammation and injury, and whether a protective ventilation strategy could mitigate the response.MethodsPregnant ewes (n = 18) received intra-amniotic lipopolysaccharide (LPS) 2 days before delivery, instrumentation and ventilation at 127±1 days gestation. Lambs were either immediately euthanased and used as unventilated controls (LPSUVC; n = 6), or were ventilated using an injurious high VT strategy (LPSINJ; n = 5) or a protective ventilation strategy (LPSPROT; n = 7) for a total of 90 min. Mean arterial pressure, heart rate and cerebral haemodynamics and oxygenation were measured continuously. Lungs and brains underwent molecular and histological assessment of inflammation and injury.ResultsLPSINJ lambs had poorer oxygenation than LPSPROT lambs. Ventilation requirements and cardiopulmonary and systemic haemodynamics were not different between ventilation strategies. Compared to unventilated lambs, LPSINJ and LPSPROT lambs had increases in pro-inflammatory cytokine expression within the lungs and brain, and increased astrogliosis (p<0.02) and cell death (p<0.05) in the WM, which were equivalent in magnitude between groups.ConclusionsVentilation after acute chorioamnionitis, irrespective of strategy used, increases haemodynamic instability and lung and cerebral inflammation and injury. Mechanical ventilation is a potential contributor to WM injury in infants exposed to chorioamnionitis.

Project description:BackgroundBronchopulmonary dysplasia (BPD) is closely associated with ventilator-induced lung injury (VILI) in very preterm infants. The greatest risk of VILI may be in the immediate period after birth, when the lungs are surfactant deficient, still partially filled with liquid and not uniformly aerated. However, there have been very few studies that have examined this immediate post-birth period and identified the initial injury-related pathways that are activated. We aimed to determine if the early response genes; connective tissue growth factor (CTGF), cysteine rich-61 (CYR61) and early growth response 1 (EGR1), were rapidly induced by VILI in preterm lambs and whether ventilation with different tidal volumes caused different inflammatory cytokine and early response gene expression.MethodsTo identify early markers of VILI, preterm lambs (132 d gestational age; GA, term approximately 147 d) were resuscitated with an injurious ventilation strategy (V(T) 20 mL/kg for 15 min) then gently ventilated (5 mL/kg) for 15, 30, 60 or 120 min (n = 4 in each). To determine if early response genes and inflammatory cytokines were differentially regulated by different ventilation strategies, separate groups of preterm lambs (125 d GA; n = 5 in each) were ventilated from birth with a V(T) of 5 (VG5) or 10 mL/kg (VG10) for 135 minutes. Lung gene expression levels were compared to levels prior to ventilation in age-matched control fetuses.ResultsCTGF, CYR61 and EGR1 lung mRNA levels were increased approximately 25, 50 and 120-fold respectively (p < 0.05), within 30 minutes of injurious ventilation. VG5 and VG10 caused significant increases in CTGF, CYR61, EGR1, IL1- , IL-6 and IL-8 mRNA levels compared to control levels. CTGF, CYR61, IL-6 and IL-8 expression levels were higher in VG10 than VG5 lambs; although only the IL-6 and CYR61 mRNA levels reached significance.ConclusionCTGF, CYR61 and EGR1 may be novel early markers of lung injury and mechanical ventilation from birth using relatively low tidal volumes may be less injurious than using higher tidal volumes.

Dataset Information

Diffusion Tensor Imaging Colour Mapping Threshold for Identification of Ventilation-Induced Brain Injury after Intrauterine Inflammation in Preterm Lambs.

Purpose

Hypothesis

Methods

Results

Conclusion

Publications

Diffusion Tensor Imaging Colour Mapping Threshold for Identification of Ventilation-Induced Brain Injury after Intrauterine Inflammation in Preterm Lambs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets