Detection and mapping of delays in early cortical folding in fetuses with ventriculomegaly from in utero MRI

tissue maps. Age-related changes in local surface curvature at each vertex v were modeled as H(v,t) = Hn(v,t) + Hd(v) = b0(v) + b1(v)t + b2(v)t 2 + a0(v) with coefficients found through joint least squares fitting to mean curvature measurements H(v,t) mapped from normal controls and IMVM subjects with gestational ages t. The quadratic term Hn(v,t) = b0(v) + b1(v)t + b2(v)t 2 represented the temporal pattern of normal cortical folding at vertex v whereas the constant delay term Hd(v) = a0(v) captured the vertex-specific difference in local surface curvature of IMVM subjects with respect to normal controls. The statistical significance of the folding delay term Hd(v) at each vertex v was evaluated using permutation testing. RESULTS Figure 1 shows multiple views of the population-average inner cortical surface with values of the folding delay term Hd(v) estimated at each vertex v. Cool colors indicate regions of the brain surface with lesser concavity (delayed sulcation) in IMVM subjects with respect to normal controls; warm colors indicate regions with lesser convexity (delayed gyrification) in IMVM subjects with respect to normal controls. Figure 2 shows the T-statistic map of the folding delay term Hd(v) thresholded at p = 0.05 (corrected). Significant delays in early cortical folding in fetuses with IMVM were detected bilaterally in the region of the parieto-occipital sulcus, confirming previous qualitative findings of the fetal neuroradiologists. Delays in early cortical folding at other locations, although visible in Fig. 1, were not significant indicating that the differences between the IMVM group and normal controls were not larger than the variability present among subjects with normal brain development. CONCLUSIONS Local alterations in early cortical folding occur in fetuses with IMVM compared with subjects with normal brain development. Additional analysis with older fetuses is needed to determine whether these differences in sulcation are transient or persist into later gestation. Further studies on a larger population will analyze the correlation between delays in cortical folding detected from antenatal MRI and postnatal neurodevelopmental outcomes.