Development of cerebellar connectivity in human fetal brains revealed by high angular resolution diffusion tractography

Abstract

High angular resolution diffusion imaging (HARDI) tractography has provided insight into major white matter pathways and cortical development in the human fetal cerebrum. Our objective in this study was to further apply HARDI tracography to the developing human cerebellum ranging in fetal and adult stages, to outline in broad strokes the 3-dimensional development of white matter and local gray matter organization in the cerebellum. We imaged intact fixed fetal cerebellum specimens at 17 gestational weeks (W), 21W, 31W, 36W, and 38W along with an adult cerebellum for comparison. At the studied earliest gestational age (17W), coherent pathways that formed the superior, middle, inferior cerebellar peduncles were already detected, but pathways between deep cerebellar nuclei and the cortex were not observed until after 38W. At 36–38W, we identified emerging regional specification of the middle cerebellar peduncle. In the cerebellar cortex, we observed disappearance of radial organization in the sagittal orientation during the studied developmental stages similar to our previous observations in developing cerebral cortex. In contrast, in the axial orientation, cerebellar cortical pathways emerged first sparsely (31W) and then with increased prominence at 36–38W with pathways detected both in the radial and tangential directions to the cortical surface. The cerebellar vermis first contained only tangential pathways to the long axes of folia (17–21W), but pathways parallel to the long axes of folia emerged between 21–31W. Our results show the potential for tractography to image developing cerebellar connectivity using HARDI tractography.

Cerebellar Pathways in Mouse Model of Purkinje Cell Degeneration Detected by High-Angular Resolution Diffusion Imaging Tractography

“…This study used HARDI tractography in an attempt to identify degeneration of fiber pathways in the cerebellum. In our previous tractography study on normal human brains, we successfully identified multiple different components of cerebellar fiber pathways at developing ages [14] and in adults [15]. We found that, in the cerebellar cortex, tractography detected tangential coherence superficially in the cerebellar cortex and revealed axonal fibers coursing parallel to the long axis of the folia and thus consistent with the location and orientation of parallel fibers in the molecular layer.…”

High‐angular resolution diffusion imaging tractography of cerebellar pathways from newborns to young adults

“…This in vivo study does not provide the same level of detail of previous ex vivo studies (Takahashi, Hayashi, Schmahmann, & Ellen Grant, 2014; Takahashi et al., 2013) due to the inherit limitations of studying living subjects; however, it may provide a more practical preliminary point of reference for clinical pediatric neuroradiologists. Using the same spatial resolution under the same MR coil across subjects with different ages, smaller brains would likely be more affected by partial volume effects as compared to larger brains.…”

Tract Profiles of the Cerebellar White Matter Pathways in Children and Adolescents

“…This explanation of the variations is supported by the observation that MD, RD and AD differentially contributed to changes in FA in the ICP, MCP and SCP. Follow-up studies would be able to explore the contribution of crossing fibers to diffusion properties of cerebellar pathways through the use of complex diffusion models (47, 48). In addition, future studies can correlate FA or other diffusion properties of the peduncles with motor, cognitive or emotional functions in which the cerebellum has been implicated (1, 2, 4, 6, 49).…”