Early detection of ventilation-induced brain injury using magnetic resonance spectroscopy and diffusion tensor imaging: an in vivo study in preterm lambs

Béatrice Skiöld; Qizhu Wu; Stuart B Hooper; Peter G Davis; Richard McIntyre; Mary Tolcos; James Pearson; Ruth Vreys; Gary F Egan; Samantha K Barton; Jeanie L Y Cheong; Graeme R Polglase

doi:10.1371/journal.pone.0095804

Early detection of ventilation-induced brain injury using magnetic resonance spectroscopy and diffusion tensor imaging: an in vivo study in preterm lambs

PLoS One. 2014 Apr 23;9(4):e95804. doi: 10.1371/journal.pone.0095804. eCollection 2014.

Authors

Affiliations

¹ Neonatal Services, The Royal Women's Hospital, Melbourne, Victoria, Australia.
² Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia; CSIRO Materials Science and Engineering, Clayton, Victoria, Australia.
³ The Ritchie Centre, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia; Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
⁴ Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia.
⁵ The Ritchie Centre, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.
⁶ Neonatal Services, The Royal Women's Hospital, Melbourne, Victoria, Australia; Victorian Infant Brain Studies, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia; Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia.

Abstract

Background and aim: 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.

Methods: Newborn 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.

Results: No 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.

Conclusion: Acute 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Brain Injuries / diagnosis*
Brain Injuries / etiology*
Diffusion Tensor Imaging / methods*
Magnetic Resonance Imaging / methods*
Respiration, Artificial / adverse effects*
Sheep, Domestic

Grants and funding

This research was supported by the Swedish Medical Society, the Swedish Brain Foundation, Sällskapet Barnavård, the Rebecca L. Cooper Medical Research Foundation, Monash University Researcher Accelerator Grant, Monash Biomedical Imaging, NH&MRC Research Fellowship (GRP: 1026890), NHMRC Early Career Fellowship (ID 1053787 to JC) and the Victorian Government's Operational Infrastructure Support Program. Chiesi Farmaceutici S.p.A. generously donated the surfactant used in this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.