Correlation between diffusion tensor imaging and histological brain injury in ventilated preterm lambs

Objective: Inflammation and mechanical ventilation contribute additively to white matter injury in the preterm infant. We examined whether in vivo diffusion tensor imaging (DTI) indices correlate with immunohistochemical analyses of brain inflammation and injury caused by injurious ventilation at birth, in the presence or absence of intrauterine inflammation. Methods: Twin-bearing ewes received an ultrasound guided injection of lipopolysaccharide (LPS; n=11) or saline (n=12) 7 days prior to delivery at ~125 days gestation. Immediately after delivery, lambs received either an injurious (LPS+INJ; n=5 and INJ; n=6) or protective (LPS+PROT; n=6 and PROT; n=5) ventilation strategy for 90 min, after which DTI was assessed. Following imaging, neuronal density (NeuN antibody) in the thalamus (Th) and myelin density (myelin basic protein, MBP) in the internal capsule (IC) and periventricular white matter (PVWM) were assessed. Results: LPS exposure significantly increased axial diffusivity (P=0.01) and decreased myelin density in the IC (P=0.02) compared to saline groups. Moreover, there was a strong inverse correlation between fractional anisotropy values and myelin density in PVWM (P=0.01), and a trend in the IC (P=0.07) in all lambs. Injurious ventilation tended to reduce radial and mean diffusivity in the Th (P=0.07 and P=0.08). Conclusion: DTI was able to detect microstructural changes associated with a reduction in myelination due to inflammation in the short term. However, DTI indices were not sensitive enough to consistently detect the microstructural changes induced by injurious ventilation immediately after birth.