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

Alahmari, Dhafer M.; Skiöld, Béatrice; Barton, Samantha K.; Nitsos, Ilias; McDonald, Courtney; Miller, Stephanie; Zahra, Valerie; Galinsky, Robert; Wu, Qisong; Farrell, Michael J.; Moss, Timothy; Hooper, Stuart B.; Pearson, James T.; Polglase, Graeme R.

doi:10.3389/fped.2017.00070

Cited by 4 publications

(16 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MRI acquisition protocols were conducted as per previously published [ 13 , 14 ]. Following stabilisation, lambs were transferred to the 3T MRI system (Siemens Skyra, Erlangen, Germany) at Monash Biomedical Imaging (Clayton, Australia), with a 15-channel radio frequency coil for transmission and reception.…”

Section: Methodsmentioning

confidence: 99%

“…Lambs were placed in supine position, and ventilation was maintained using a BabyPAC portable and MR-compatible ventilator (Pneupac, Smiths Medical, UK). Brain MRI included structural imaging sequences (T1, T2), susceptibility-weighted imaging (SWI), DTI, and single-voxel MRS [ 13 , 14 ]. The total acquisition time was about 40 min.…”

Section: Methodsmentioning

confidence: 99%

“…First, the FDT toolbox was used to correct all DTI data for eddy-current distortion, and then DTI parametric maps of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) were created with the FMRIB Diffusion Toolbox. All maps were co-registered with high-resolution T2 images of the brains using the Linear Image Registration Tool (FLIRT [ 18 ]), with the b = 0 image used as a reference [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

“…ROIs were defined manually on the high-resolution T2 images of each lamb and then transformed to the corresponding FA, AD, MD, and RD maps to calculate the mean regional values for each lamb [ 13 , 14 ]. ROIs were placed in the thalamus (Th), periventricular white matter (PVWM), IC, frontal white matter (FWM), and cerebellum (CB) vermis, targeting the stalk and midline WM ( S1 Fig ).…”

Section: Methodsmentioning

confidence: 99%

“…Our studies have demonstrated that as little as 15 min of high V T ventilation can increase early markers of brain injury through two key pathways: 1) initiation of a systemic inflammatory cascade resulting in cerebral inflammation and injury; and 2) haemodynamic instability resulting in fluctuations in cerebral blood flow and pressure [ 10 , 12 ]. Early markers of brain injury can be detected within 1–2 h after birth using histological techniques [ 12 ] as well as advanced magnetic resonance imaging (MRI) [ 13 , 14 ]. However, it is unlikely that infants can undergo MRI so soon after birth.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Diffusion tensor imaging detects ventilation-induced brain injury in preterm lambs

et al. 2017

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Diffusion tensor imaging detects ventilation-induced brain injury in preterm lambs

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

Assessing Spinal Cord Injury Area in Patients with Tethered Cord Syndrome by Diffusion Tensor Imaging

Wang

et al. 2019

World Neurosurgery

View full text Add to dashboard Cite

Early administration of umbilical cord blood cells following brief high tidal volume ventilation in preterm sheep: a cautionary tale

Tran,

Penny,

Chan

et al. 2024

J Neuroinflammation

Self Cite

View full text Add to dashboard Cite

Background Umbilical cord blood (UCB) cells are a promising treatment for preterm brain injury. Access to allogeneic sources of UCB cells offer the potential for early administration to optimise their therapeutic capacities. As preterm infants often require ventilatory support, which can contribute to preterm brain injury, we investigated the efficacy of early UCB cell administration following ventilation to reduce white matter inflammation and injury. Methods Preterm fetal sheep (0.85 gestation) were randomly allocated to no ventilation (SHAM; n = 5) or 15 min ex utero high tidal volume ventilation. One hour following ventilation, fetuses were randomly allocated to i.v. administration of saline (VENT; n = 7) or allogeneic term-derived UCB cells (24.5 ± 5.0 million cells/kg; VENT + UCB; n = 7). Twenty-four hours after ventilation, lambs were delivered for magnetic resonance imaging and post-mortem brain tissue collected. Arterial plasma was collected throughout the experiment for cytokine analyses. To further investigate the results from the in vivo study, mononuclear cells (MNCs) isolated from human UCB were subjected to in vitro cytokine-spiked culture medium (TNFα and/or IFNγ; 10 ng/mL; n = 3/group) for 16 h then supernatant and cells collected for protein and mRNA assessments respectively. Results In VENT + UCB lambs, systemic IFNγ levels increased and by 24 h, there was white matter neuroglial activation, vascular damage, reduced oligodendrocytes, and increased average, radial and mean diffusivity compared to VENT and SHAM. No evidence of white matter inflammation or injury was present in VENT lambs, except for mRNA downregulation of OCLN and CLDN1 compared to SHAM. In vitro, MNCs subjected to TNFα and/or IFNγ displayed both pro- and anti-inflammatory characteristics indicated by changes in cytokine (IL-18 & IL-10) and growth factor (BDNF & VEGF) gene and protein expression compared to controls. Conclusions UCB cells administered early after brief high tidal volume ventilation in preterm fetal sheep causes white matter injury, and the mechanisms underlying these changes are likely dysregulated responses of the UCB cells to the degree of injury/inflammation already present. If immunomodulatory therapies such as UCB cells are to become a therapeutic strategy for preterm brain injury, especially after ventilation, our study suggests that the inflammatory state of the preterm infant should be considered when timing UCB cells administration.

show abstract

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

Cited by 4 publications

References 45 publications

Diffusion tensor imaging detects ventilation-induced brain injury in preterm lambs

Diffusion tensor imaging detects ventilation-induced brain injury in preterm lambs

Assessing Spinal Cord Injury Area in Patients with Tethered Cord Syndrome by Diffusion Tensor Imaging

Early administration of umbilical cord blood cells following brief high tidal volume ventilation in preterm sheep: a cautionary tale

Contact Info

Product

Resources

About