The following experiments were performed using clinical MR scans of 40 fetal subjects at gestational ages ranging from 20.57 to 27.86 weeks. The mothers were referred for fetal MRI due to questionable abnormalities on prenatal ultrasound or a prior abnormal pregnancy. All women had normal fetal MRI and all newborns have had normal postnatal neurodevelopment. Fetal imaging was performed in our institution on a 1.5T scanner (GE Healthcare, Mulwaukee, WI) without sedation of the mother or the fetus. For each subject multiple stacks of single-shot fast spin-echo (SSFSE) T2-weighted slice images (pixel size 1 mm × 1 mm, slice thickness ≈ 3 mm) re acquired in the approximately axial, sagittal and coronal planes with respect to the fetal brain. The MR sequence parameters (TR = 4500 ms, TE = 91 ms) were originally designed for clinical scans and cannot be adjusted for image analysis purposes. High resolution 3D volumes were reconstructed from 2D slice MR images using the slice intersection motion correction (SIMC) technique [14
]. The reconstructed volumes were automatically segmented into individual tissue types (developing grey matter, developing white matter, the germinal matrix) using an atlas-based approach with probabilistic atlases generated from a spatiotemporal model of the fetal brain [15
]. Smoothed tissue segmentation atlases were then used with a template free elastic registration method [16
] to spatially normalize the subjects. For each subject, the Jacobian matrix maps were computed, from the resulting deformation fields, to quantify the pattern of deformation required to spatially normalize individual anatomies. For each subject, we computed the DDV maps and performed multivariate, multiple linear regression on the population with age as the independent variable and the directional coefficients as the dependent variables. The regression coefficients were tested for statistical significance. We also computed, using the DDV maps, a PGD map for the subject population.
3.1 Results and Discussion
shows the principal growth direction for the given age range overlaid on the spatially normalized average MRI, and displayed using the Rview software5
. Overall growth shows a distinct spatial pattern. The intermediate zone (developing white matter (WM)), along the most dorsal and ventral areas, is growing primarily in the anterior-posterior (A-P) direction during this period. Along the cortical plate, PGD alternates between superior-inferior (S-I) and right-left (R-L) growth direction corresponding to the formation of sulci and gyri respectively. At the sylvian fissure we see that the growth is primarily along the R-L direction corresponding to the deepening of the fissure. The ventricles do not show a clear direction of growth as during this period in fetal brain development, the ventricles do not change significantly in absolute size as the brain grows.
Fig. 2 Principal growth direction (PGD) vectors for the group of fetal anatomies studied. Each reference anatomical direction is indicated by one color: red = left-right (R-L); green = anterior-posterior (A-P); blue = superior-inferior (S-I). The panels from (more ...)
shows the regions where directional growth has changed significantly with age. The regions showing significant changes correspond to regions of major cortical folding. The largest cluster of significant voxels occur at the sylvian fissure where the significant acceleration of growth in the R-L direction and deceleration along the S-I direction indicate deepening of the fissure. As indicated by the cross-hairs, we see that the in addition to growth acceleration in the R-L direction, there is also a A-P growth component indicating “flattening” of the superior aspect of the temporal lobe at the sylvian fissure. To accommodate these changes in the cortical regions, we see that the intermediate zone underlying the fissure is being “stretched” in the S-I direction its growth in the R-L direction is restricted by neighboring structures.
Fig. 3 Growth rate maps showing regions exhibiting significant change in growth direction with age. Row (a): Regions showing accelerated growth the associated anatomical direction. Row (b): Regions showing decelerated growth and the associated anatomical direction. (more ...)
Considering both and together, we see that brain growth is characterized by spatially varying, directional growth. In some regions this directionality does not change significantly as the fetus matures. For example, the intermediate zone which showed a very strong A-P growth direction in does not exhibit significant accelerations and decelerations in any direction in the period of growth considered for this study. Major shape changes in the cortex occur due to significant changes in directional growth at sites of sulci and gyri. The effect of these changes in direction on underlying tissue is determined by the rate of those changes in the given time-period. For example, the rate of directional change associated with the formation of the calcrine sulcus is not large enough to significantly change directions in the underlying WM. In comparison, the formation of the sylvian fissure occurs at a more rapid rate and thereby significantly changes growth directionality both in the cortex and the underlying WM.