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


CONCLUSIONS
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.
Neonatal Services, The Royal Women's Hospital, Melbourne, Victoria, Australia.
Béatrice
B
Skiöld
Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia; CSIRO Materials Science and Engineering, Clayton, Victoria, Australia.
Qizhu
Q
Wu
The Ritchie Centre, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia; Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
Stuart B
SB
Hooper
Neonatal Services, The Royal Women's Hospital, Melbourne, Victoria, Australia.
Peter G
PG
Davis
Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia.
Richard
R
McIntyre
The Ritchie Centre, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.
Mary
M
Tolcos
Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia.
James
J
Pearson
Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia.
Ruth
R
Vreys
Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia.
Gary F
GF
Egan
The Ritchie Centre, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.
Samantha K
SK
Barton
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.
Jeanie L Y
JL
Cheong
The Ritchie Centre, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia; Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
Graeme R
GR
Polglase
D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000175:diagnosis* / Q000209:etiology*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D012121:Respiration, Artificial / Q000009:adverse effects*; D034561:Sheep, Domestic