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.

In utero administration of Ad5 and AAV pseudotypes to the fetal brain leads to efficient, widespread and long-term gene expression

“…If we were to use an anatomical marker as an example, then diffusion sensor magnetic resonance imaging has shown that the cortical and subplate in humans thickens in the second trimester of human fetal development. 41 However, this occurs later at E14-18 in the fetal mouse gestational period. 42 Again, this raises the importance of larger animal studies, in particular non-human primates, to provide a more representative model.…”

The emergence of functional architecture during early brain development

“…During the waiting period, which lasts approximately four weeks, afferents receive instructive input and start projecting onto their cortical targets. Concurrently, the corpus callosum extends in an anterior to posterior fashion (Huang et al, 2009(Huang et al, , 2006, first synapsing on neurons in the transient subplate zone before establishing its definitive connections in the cortical plate (Kostovic and Jovanov-Milosevic, 2006;Volpe, 2009). Once thalamocortical connections are established, which has been noted to occur between 24-32 PCW (Figure 2), sensory stimuli including visual and auditory input can reach the developing cortex (Kostovic and Jovanov-Milosevic, 2006).…”

“…Early afferent fibers appear from as early as 8-10 PCW forming the cerebral stalk at the level of the thalamus . High field DWI studies have demonstrated the emergence of projection-and commissural fibers, including the internal capsule and corpus callosum from as early as 13 and 15 PCW respectively (Huang et al, 2009;Takahashi et al, 2012) (Figure 2). …”

“…Similar to the adult connectome, the neonatal brain has repeatedly been found to display short characteristic path length, which is computed as the average number of edges that need to be Schematic overview based on findings by (Alcauter et al, 2014;Bystron et al, 2008;Gao et al, 2011;Innocenti and Price, 2005;Kostovic et al, 2014;Kostovic and Rakic, 1980;Kostovic and Vasung, 2009;Shankle et al, 1999;Stiles and Jernigan, 2010;Thomason et al, 2013Thomason et al, , 2015Vanhatalo and Kaila, 2006;Vasung et al, 2010) (Huang et al, 2009;Kostovic and Jovanov-Milosevic, 2006;Takahashi et al, 2012;Vasung et al, 2010). (Doria et al, 2010a;Gao et al, 2014a;Smyser et al, 2010;Thomason et al, 2015).…”

Structural Development of Human Fetal and Preterm Brain Cortical Plate Based on Population-Averaged Templates

“…The anterior commissure (AC) can be clearly identified in DTI color-encoded map (see, e.g., Huang et al 2009) and was aligned with the upper edge of the rectum in the single-subject template at 20 weeks. Population-averaged FA maps and DTI color-encoded maps at 20 weeks were generated with affine (Woods et al 1998) and LDDMM transformation.…”