We have provided the first DTI atlas and quantitatively assessed the volume, primary eigenvector/surface angle and thickness of CP+SP during the second trimester of human fetal brain development. Our study demonstrates that DTI provides a unique probe to systematically characterize the neuroanatomy of the developing human brain. Specifically, we have (1) identified the age when the uncinate fasciculus and inferior longitudinal fasciculus become apparent, (2) revealed the volume increase of basal ganglia and ganglionic eminences and observed an inhomogeneous increase in the thickness of the CP+SP, and (3) found that columnar structures become detectable with DTI at ~ 13 weeks or earlier. Using 3D reconstruction, we were also able to identify the sequence of sulcal formation and observed the following order: Sylvian fissure, calcarine fissure, central sulcus, and parieto-occipital sulcus.
Much of our anatomical knowledge of human fetal brain development is based on histological analysis, and there are a surprisingly small number of such studies that systematically describe the developmental processes of the human brain. Most of the available atlases are schematics and photographs (O’Rahilly and Muller, 1999
). Recently published histological atlases by Bayer and Altman (2004
are excellent resources. Although MRI-based anatomical studies cannot provide anatomical information as detailed as that provided by histology, MRI excels in characterizing the 3D architecture of the developing brain. The analysis of growing axonal bundles, in particular, is difficult to study with histology-based techniques. The use of MRI-based techniques, together with histology, can enhance our understanding of the dynamics of human brain development (Kostović et al., 2002
During the second trimester, significant changes were observed in the white matter, most dramatic of which were that the uncinate fasciculus, inferior longitudinal fasciculus, and corpus callosum became apparent. The limbic tracts developed earliest, and were visible in color-encoded maps by 13 gestational weeks. Ren et al. (2006)
have reported the formation of the corpus callosum at ~ 15 gestational weeks. Among the commissural tracts, the anterior commissure and optic chiasm appear earlier than the corpus callosum (). After the initial appearance of the corpus callosum, it extends in both anterior and posterior directions during the following weeks. At 19 weeks gestation, it undergoes more anterior development (Huang et al., 2006b
). Projection fibers can be delineated at 13 weeks, and develop to its peripheral regions during the second trimester. We observed the uncinate fasciculus and inferior longitudinal fasciculus become apparent at 15 gestational weeks, and no association fibers could be identified in the 13 gestational week brain. The visibility of different white matter tracts was restricted by the quality of the samples and the resolution of the images. Most fibers in the cerebrum, with a pronounced appearance, can be revealed with our data set (200–400 µm). However, some fibers, such as superior cerebellar peduncle, can be observed in histological studies (Bayer and Altman, 2005
), but not in our DTI images. Therefore, it is possible that some existent fibers were not identified in DTI images.
We examined the development of the cerebral wall macroscopically and found that the laminar pattern in our DTI images was consistent with findings from histological slides and T1
-weighted images (Kostović et al., 2002
). From 13 to 21 weeks gestation, the laminar structures of the cerebral wall, which consists of multiple layers (), can be observed. The lateral and medial views of the three-dimensional reconstruction of one hemisphere reveal the order of sulcal formation. Although large sulci have formed by the end of the second trimester, the brain surface is still smooth, and most of the folding of the cerebral cortex takes place later in fetal development. The thickening pattern of the CP+SP during the second trimester is similar to that of the mouse from E14 to E18 (Zhang et al., 2003
), suggesting that the mechanisms regulating the increase of CP+SP may be evolutionarily conserved.
We also characterized the development of the cerebral wall microscopically by delineating the orientations of microstructures with diffusion tensor primary eigenvector. McKinstry et al. (McKinstry et al., 2002
) clearly identified the radial structure in vivo
in 26 week fetal brains. They have also found that the radial organization disappears by 36 weeks. Our study revealed that the radial organization begins to appear at 13 weeks and becomes pronounced at 15 weeks. The aDWI images and vector maps () clearly show that the laminar and radial structures inter-twine throughout the second trimester. Previous studies have found that the laminar organization is predominant in the adult cerebral cortex, although it functions with the columnar units along the radial direction (Mountcastle, 1997
). Thus, it implies that the radial organization is prominent only from 13 to 36 weeks of gestational age, while the laminar organization may exist throughout brain development.
We reconstructed major subcortical neural structures three dimensionally to demonstrate their morphological changes. Furthermore, we measured the volumes of the neural structures throughout the second trimester. There was almost a constant volume increase for the basal ganglia and the ganglionic eminences. The ganglionic eminences are developmental structures that differentiate during the third trimester into the caudate, the putamen, the globus pallidus, and the basal ganglia. The expansion of these subcortical structures is accompanied by the shrinkage of the ventricle. Global changes of these structures have been reported in this study qualitatively and quantitatively. Compared with histological studies, MRI has the advantage of providing a convenient three-dimensional reconstruction and quantitative assessment of volume and area. These two modalities provide complementary information about the dynamic changes that occur during brain development.