Introduction: In neonates with single ventricle (SV), reduced cerebral white matter (WM) microstructural development at birth has been associated with smaller ascending aorta size, presumably indicating the effect of lower antegrade cerebral blood flow in utero. We sought to determine whether the relationship between ascending aortic size and WM microstructure persists into adolescence.
Hypothesis: Smaller ascending aortic z-score (AOZ) at birth will predict reduced WM microstructure in adolescence.
Methods: AOZ was obtained from the first echo after birth prior to surgical intervention. Diffusion tensor imaging was used to obtain fractional anisotropy (FA), the primary outcome, as well as mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Means were calculated for 20 major fiber tracts based on a standard atlas. Partial Spearman correlations evaluated the associations between AOZ and regional WM microstructure measures, adjusting for age at MRI, sex, scanner field strength, and Norwood status.
Results: Among 42 Fontan adolescents, aged 10-19 years, 31 had undergone the Norwood procedure as neonates. Smaller AOZ at birth correlated with lower FA in the bilateral inferior longitudinal fasciculus (R: r=.43, P=.008; L: r=.40, P=.01), right (R) cingulum-hippocampus bundle (r=.34, P=.04), left (L) inferior fronto-occipital fasciculus (r=.32, P=.048), L arcuate fasciculus (r=.42, P= .008), and L superior longitudinal fasciculus (r=.38, P=.02; see Figure). There was a trend towards correlation in the R inferior fronto-occipital fasciculus (r=.31, P=.054) and L cingulum-cingulate bundle (r=.31, P=.055). MD, AD, and RD demonstrated similar patterns of findings.
Conclusions: Among patients with SV, smaller AOZ at birth is associated with persistent reduction in WM microstructure in certain WM tracts. These regions receive terminal blood flow in the fetus/neonate and may be most vulnerable to long-term injury from hypoperfusion.