Neocortex Organization and Connectivity in Fetal Human Brains Revealed by Diffusion Tractography and Histology

Introduction: During the late fetal period and early preterm period, the most prominent transient layer is the subplate (SP) zone, located between the immature cortex (cortical plate; CP) and the immature white matter (intermediate zone; IZ), which contains awaiting thalamo-cortical afferent fibers that cross one another [1-3]. The SP is especially thick in humans which develops around prenatal W13 and gradually disappears after W32–34 [1, 3] and contains complex crossing pathways. Resolving accurate pathways running through the unmyelinated subcortical areas is critical to image the entire length of fiber pathways in the developing brain. High-angular resolution diffusion imaging (HARDI) has been proposed as an alternative to diffusion tensor imaging (DTI) for improved resolution of crossing fiber pathways [4], and is effective for delineating the structural changes that occur in developing fetal (preterm) brains [5, 6]. Here, we applied HARDI tractography to intact whole postmortem fetal human brains to explore the 3-dimensional evolution of the CP and SP into the mature cortical and immediately subcortical structure. We compared HARDI tractography, fractional anisotropy (FA), and histological measures (Hematoxilin and Eosin (HE) and Luxol Fast Blue (LFB)).