Background: Fetal growth restriction (FGR) is a pregnancy complication associated with risk of adverse neurodevelopment. Current imaging techniques are not sensitive enough to detect subtle structural abnormalities in FGR brain. We examined whether advanced MRI analysis techniques can detect brain injury caused by FGR.
Methods: Surgery was undertaken in twin bearing pregnant ewes at 88 days gestation (term, 147 days) to induce FGR in one fetus. At 127 days gestation, FGR and control (appropriate for gestational age, AGA) lambs were delivered, intubated and ventilated. Conventional and advanced brain imaging was conducted using a 3T MRI scanner. T1-weighted (T1w) and T2-weighted (T2w) imaging, magnetic resonance spectroscopy (MRS), and diffusion MRI (dMRI) data were acquired. Diffusion tensor imaging (DTI) modelling and analysis, and fixel-based analysis of 3-tissue constrained spherical deconvolution (CSD) of dMRI data was performed to compare FGR and AGA lamb scans. Lambs were euthanised after the scans and brain histology was performed.
Results: FGR and AGA lamb (body weight, mean (SD): 2.2(0.5) vs. 3.3(0.3) kg, p=0.002) MRI brain scans were analysed. There were no statistically significant differences observed between groups in conventional T1w, T2w or MRS brain data. DTI indices also did not show any statistically significant differences between groups in the ROIs. Fixel-based analysis, however did reveal a decrease in fibre cross-section (FC, p<0.05) but not in fibre density (FD) or fibre density and cross-section (FDC) in FGR vs. AGA lamb brains. The specific tracts were in the periventricular white matter, hippocampus and cerebellar white matter, and were supported by histological evidence of white matter loss in corresponding FGR brain regions.
Conclusions: Neuropathology associated with FGR is subtle and imaging detection may require advanced MRI analysis. Fixel-based analysis of 3-tissue CSD offers potential to measure tract-specific differences in brain structure, not seen on conventional imaging or DTI modelling.