Microstructural changes of the baboon cerebral cortex during gestational development reflected in magnetic resonance imaging diffusion anisotropy

Abstract

Cerebral cortical development involves complex changes in cellular architecture and connectivity that occur at regionally varying rates. Using diffusion tensor magnetic resonance imaging (DTI) to analyze cortical microstructure, previous studies have shown that cortical maturation is associated with a progressive decline in water diffusion anisotropy. We applied high-resolution DTI to fixed postmortem fetal baboon brains and characterized regional changes in diffusion anisotropy using surface-based visualization methods. Anisotropy values vary within the thickness of the cortical sheet, being higher in superficial layers. At a regional level, anisotropy at embryonic day 90 (E90; 0.5 term; gestation lasts 185 d in this species) is low in allocortical and periallocortical regions near the frontotemporal junction and is uniformly high throughout isocortex. At E125 (0.66 term), regions having relatively low anisotropy (greater maturity) include cortex in and near the Sylvian fissure and the precentral gyrus. By E146 (0.8 term), cortical anisotropy values are uniformly low and show less regional variation. Expansion of cortical surface area does not occur uniformly in all regions. Measured using surface-based methods, cortical expansion over E125-E146 was larger in parietal, medial occipital, and lateral frontal regions than in inferior temporal, lateral occipital, and orbitofrontal regions. However, the overall correlation between the degree of cortical expansion and cortical anisotropy is modest. These results extend our understanding of cortical development revealed by histologic methods. The approach presented here can be applied in vivo to the study of normal brain development and its disruption in human infants and experimental animal models.

Figure 1.

Isocortical versus allocortical diffusion anisotropy at E90. a–k, Coronal slices (a–h) of RA maps are shown for locations indicated on the surface models (i, j, k). Coronal slices f–h are enlargements of slices b–d to show detail. The classification of surface structures used is illustrated on slices f–h. Isocortex is shown in blue, “other cortex” (including allocortex) in green, unassigned cortex in brown, and the “medial wall” (not containing cortex) in gray. In f–h, a thicker cortical surface ribbon indicates greater cortical curvature in the through-plane direction. The anisotropy color scale for “volume data” (a–h) differs from the surface anisotropy color scale (i–l); however, in both cases, yellow is most anisotropic. At the location of the isocortex/allocortex boundary, a dramatic change in cortical diffusion anisotropy (high-isocortex/low-allocortex) is observed. In the ventral view inset (l), a color code is used to show the location of proisocortical areas Iai, Iam, and 13a described by Ferry et al. (2000) using surface registrations to the adult macaque atlas surface (for details, see Results, Cortical diffusion anisotropy at E90).

Figure 2.

Heterogeneity in isocortical diffusion anisotropy at E125. In each image plane, the intersection of the right hemisphere isocortical surface is shown in blue. a, Laminar (light blue arrow) and regional (compare regions near yellow and red arrows) patterns of anisotropy variation are observable. Regional variation is also apparent in the coronal views (b, c; positions of these image planes are indicated by dashed lines in a, d, and e). For example, anisotropy caudal/inferior to the STS is larger than rostral/superior to the STS. The dotted blue line in e indicates the medial extent of the parahippocampal gyrus.

Figure 3.

Cortical diffusion anisotropy at E146. The dotted blue line indicates the medial extent of the parahippocampal gyrus.

Figure 4.

Relative anisotropy versus cortical depth. a, The mean RA (<RA>) is plotted versus depth from the brain surface. Cortical thickness was estimated from H&E stained sections of brains ranging in age from E90 to E185, and is represented here as dashed vertical lines. To account for postfixation shrinkage that occurs in the paraffin embedding procedure, a correction factor of 1.3 was determined by comparing MRI data to H&E stained E90 and E185 brains. Vertical solid lines indicate the corrected cortical thickness estimates at each age. b, H&E stained micrographs of cortical cross sections from the parietal lobe between E90 and term (E185). c, Change in baboon peak RA values (solid circles) with gestational age. The values were fitted to a polynomial to guide the eye (solid line). Data from living prematurely delivered human infants (McKinstry et al., 2002) are also shown (gray triangles).

Figure 5.

Intersubject variability in the pattern of isocortical diffusion anisotropy at E125. a–c, The top row displays RA for the three E125 surfaces. In d, the mean RA value from the three brains is projected onto the average E125 surface. Anisotropy values could not be measured for brain E125c in the occipital gray patch shown in the medial view (d) because of issues with RF homogeneity. This region was omitted from analysis. The dotted blue line indicates the medial extent of the parahippocampal gyrus.

Figure 6.

Regional variation in cortical diffusion anisotropy at E125. a, The geodesic distance from a surface node on the rostral border of the insula (green asterisk) is displayed for brain E125b. Relative anisotropy values obtained from 3412 unique voxels are plotted versus geodesic distance for corresponding nodes in b, and a linear fit to the data is shown to guide the eye. Similarly derived lines are presented in c for all three E125 brains. Seven functional modalities are projected onto the E125b surface in d. RA values in e are color coded according to the regions shown in d. Motor and V1 modalities are distinguished from the remaining regions in f. Solid lines are results from a three-parameter linear regression in which all voxels are fit to a single slope; non-V1 motor voxels are modeled with one intercept, and V1 motor voxels are modeled with a different intercept. The “offset” parameter listed in Table 3 is the difference between intercepts illustrated in f.

Figure 7.

Regional patterns of areal expansion (the ratio of older brain surface area/younger brain surface area) divided by the age difference in days) from E90 to E125 (top two rows), and from E125 to E146 (bottom two rows). a, Lateral and medial views of E90 standard-mesh fiducial surface with seven registration landmarks displayed. b, Lateral and medial views of the average E125 standard-mesh fiducial surface with the corresponding seven registration landmarks displayed. c, Rate of areal expansion between E90 and E125 (mean of E125a, E125b, E125c ratios relative to E90), displayed on a very inflated surface. Above-average expansion rates are evident in medial occipital and parietal cortex and dorsolateral frontal cortex; below-average expansion rates are evident in rostral cingulate cortex and ventral occipitotemporal cortex. d, Lateral and medial views of the average E125 standard-mesh fiducial surface with nine landmark contours for registration. e, Lateral and medial views of E146 standard-mesh fiducial surface, with the corresponding nine landmarks displayed. f, Areal expansion rates between E125 and E146 (mean of E146 relative to E125a, E125b, E125c ratios), displayed on a very inflated surface. The dotted black curve in a, d, and e shows the boundary used to calculate the percentage cortical surface area rostral to the superior temporal gyrus and lunate sulcus.