Anatomical characterization of human fetal brain development with diffusion tensor magnetic resonance imaging

Abstract

The human brain is extraordinarily complex, and yet its origin is a simple tubular structure. Characterizing its anatomy at different stages of human fetal brain development not only aids in understanding this highly ordered process but also provides clues to detecting abnormalities caused by genetic or environmental factors. During the second trimester of human fetal development, neural structures in the brain undergo significant morphological changes. Diffusion tensor imaging (DTI), a novel method of magnetic resonance imaging, is capable of delineating anatomical components with high contrast and revealing structures at the microscopic level. In this study, high-resolution and high-signal-to-noise-ratio DTI data of fixed tissues of second-trimester human fetal brains were acquired and analyzed. DTI color maps and tractography revealed that important white matter tracts, such as the corpus callosum and uncinate and inferior longitudinal fasciculi, become apparent during this period. Three-dimensional reconstruction shows that major brain fissures appear while most of the cerebral surface remains smooth until the end of the second trimester. A dominant radial organization was identified at 15 gestational weeks, followed by both laminar and radial architectures in the cerebral wall throughout the remainder of the second trimester. Volumetric measurements of different structures indicate that the volumes of basal ganglia and ganglionic eminence increase along with that of the whole brain, while the ventricle size decreases in the later second trimester. The developing fetal brain DTI database presented can be used for education, as an anatomical research reference, and for data registration.

Figure 1.

Layers of the developing cerebral cortex. a–c show a coronal histological slide of a 17 week fetal brain, a coronal MRI aDWI slice of a 17 week fetal brain, and an enlarged piece of the cerebral wall, respectively. In b, aDWI contrast clearly differentiates three layers that correspond to those regions in a and c. The red contour is the boundary of the cortical plate and subplate (CP+SP). The dashed red curve separates the cortical plate and subplate. The annotation of each layer is shown at the bottom right panel.

Figure 2.

Annotation on axial (a) and coronal (b) slices of fetal brains at 13, 15, 19, and 21 weeks of gestational age. The location of each plane of optical section is demonstrated as yellow lines across the brain in the top left corner of each image. White matter fibers are labeled on color-encoded maps, while other structures are labeled on aDWI images. ac, Anterior commissure; acr, anterior region of corona radiata; alic, anterior limb of internal capsule; cbt, corticobulbar tracts; cc, corpus callosum; cg, cingulum; cp, cerebral peduncle; cst, cortical spinal tract; dscp, decussation of superior cerebellar peduncle; ec, external capsule; fx, fornix; icp, inferior cerebellar peduncle; ifo, inferior fronto-occipital fasciculus; ilf, inferior longitudinal fasciculus; middle cerebellar peduncle; mcp, middle cerebellar peduncle; ml, medial lemniscus; oc, optical chiasm; on, optical nerve; plic, posterior limb of internal capsule; ros, rostrum; scp, superior cerebellar peduncle; scr, superior region of corona radiata; splen, splenium; st, stria terminalis; unc, uncinate fasciculus vof, vertical occipital fasciculus; IV Ven, fourth ventricle; Aqu, aquarium; Caud, caudate; Cblm, cerebellum; Chor Plex, choroid plexus; CP, cortical plate; FL, frontal lobe; GE, ganglionic eminence; IG, insular gyrus; Lat Ven, lateral ventricle; Put, putamen; SP, subplate; Tha, thalamus; Put, putamen.

Figure 3.

3D depiction of developmental white matter fibers. a is a lateral view of limbic tracts where pink fibers in 13, 15, and 19 week brains are the fornix and stria terminalis and purple fibers in the 19 week brains indicate the cingulum bundle. b is an oblique view of the commissural fibers, where pink and green fibers in 13, 15, and 19 week brains are the corpus callosum and the middle cerebellar peduncle, respectively. c is a lateral view of projection fibers, where red and purple fibers in 13, 15, and 19 week brains are the cerebral peduncle and the inferior cerebellar peduncle, respectively. d is a lateral view of association tracts, in which blue fibers in brains of 13 and 15 weeks are the external capsule, and green and red fibers in a brain of 19 weeks are the inferior longitudinal fasciculus/inferior fronto-occipital peduncle and uncinate fasciculus, respectively. For anatomical guidance, the thalamus (yellow structure in a–d) and the ventricles (gray structure in a, c, d) are also shown.

Figure 4.

Mammillothalamic and habenular–interpeduncular tracts in a histological slide and in axial and sagittal color-encoded maps of a 15 week fetal brain. These two tracts are annotated with green font, while other tracts are indicated with yellow font. Please see abbreviation list of Figure 2 for full names of other tracts.

Figure 5.

Three-dimensional reconstruction of the lateral (top row) and medial (bottom row) surface of 13–21 week brains to reveal the development of the Sylvian fissure (green arrow), the calcarine fissure (blue arrow), and the parieto-occipital sulcus (red arrow), respectively.

Figure 6.

Averaged thickness profiles of the CP+SP across the cortical surface for 13–21 week gestation brains (a–e). Color bar indicates the thickness. A summary of the increase in cortical growth is shown in f.

Figure 7.

Delineation of cerebral wall structures for brains of 13–21 weeks of gestational age. In a–e, aDWI images are placed on the left, and the color-encoded map is placed on the right for brains at each gestational stage. Enlarged cerebral wall in f–j reveals multiple layers. k–o depict the visualization of the primary eigenvector of the tensor within the cerebral wall.

Figure 8.

a–e, Display of the angles between the diffusion tensor primary eigenvector and normal vector of the surface triangular meshes for 13–21 week brains. Color bar indicates the quantification of the angle. Except for the brains of 13 and 15 week gestational age, most angles measured are from 0 to 10°, which is demonstrated with blue color on the surface of each brain.

Figure 9.

Three-dimensional reconstruction of the basal ganglia and ganglionic eminence (bottom row of a), ventricle (middle row of a), and whole brain (top row of a). Different colors represent different brain structures: whole brain (gray), ventricle (pink), ganglionic eminence (red), putamen and globus pallidus together (cyan), thalamus (yellow), and caudate nucleus (green). b–d show the quantitative volume and surface measurement of these structures. b and d are absolute and normalized volumes of major brain structures during the second trimester, respectively. c is the total brain volume and cerebral surface area during this period.