Disruption of neuronal migration to the cortex is responsible for a host of developmental disorders including severe cognitive impairment, epilepsy, motor and sensory abnormalities, and mild learning disabilities, which are often associated with morphometric abnormalities of the brain including polymicrogyria (PMG) and lissencephaly (US). PMG results from abnormal late cortical organization and is inconstantly associated with abnormal neuronal migration. PMG is a common cortical malformation and is associated with a wide number of patterns and syndromes and with mutations in several genes. In contrast, LIS is characterized by absent or decreased convolutions, producing cortical thickening and a smooth cerebral surface. Recently, even more subtle developmental disturbances of gyral folding have been reported to lead to developmental neurological disorders, suggesting altered brain connectivity. It is therefore essential to develop a clear picture of the patterns and timing of development of brain pathways, and to interpret the role of white matter pathways in order to more accurately diagnose brain dysfunctions during development. In order to accurately diagnose focal and global pathology of neuronal migration disorders, it is crucial to directly image fiber pathways in the whole brain. However, using non-invasive MRI techniques, detection of structural connections through the gray matter/white matter border in the human cerebral cortex remains elusive due to the existence of abundant fiber crossings in the white/gray matter border. Overcoming this problem, high-angular resolution diffusion MR imaging (HARD I) (including O-ball imaging [OBI] and diffusion spectrum imaging [DSI]) is useful to resolve fiber crossings. We have recently further optimized this technique to resolve detailed coherent and crossing structures in the brain even in tissues with low fractional anisotropy which is useful to detect pathways through pathologic regions with migration disorders. Combining the results from this study to an ongoing research program on typically developing brains (Takahashi, R01 HD078561), we will be able to assess in a 3-dimensional manner the pathology of brain pathways in PMG and LIS, which we believe will give us an important insight into the relationships between fiber pathways and gyral structures during development.

Public Health Relevance

We will have broad opportunities to apply this technique to patient populations including neurological and psychiatric disorders. Information regarding the degree to which in vivo results can reproduce ex vivo results in which regions will be important for clinical interpretation of this technique.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Small Research Grants (R03)
Project #
1R03NS091587-01
Application #
8869508
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Riddle, Robert D
Project Start
2015-03-01
Project End
2017-02-28
Budget Start
2015-03-01
Budget End
2016-02-29
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
Das, Avilash; Takahashi, Emi (2018) Characterization of White Matter Tracts by Diffusion MR Tractography in Cat and Ferret that Have Similar Gyral Patterns. Cereb Cortex 28:1338-1347
Das, Avilash; Takahashi, Emi (2018) Neuronal Migration and Axonal Pathways Linked to Human Fetal Insular Development Revealed by Diffusion MR Tractography. Cereb Cortex 28:3555-3563
Re, Thomas J; Levman, Jacob; Lim, Ashley R et al. (2017) High-angular resolution diffusion imaging tractography of cerebellar pathways from newborns to young adults. Brain Behav 7:e00589
Kanamaru, Yuri; Li, Jianxue; Stewart, Natalie et al. (2017) Cerebellar Pathways in Mouse Model of Purkinje Cell Degeneration Detected by High-Angular Resolution Diffusion Imaging Tractography. Cerebellum 16:648-655
Wilkinson, Molly; Kane, Tara; Wang, Rongpin et al. (2017) Migration Pathways of Thalamic Neurons and Development of Thalamocortical Connections in Humans Revealed by Diffusion MR Tractography. Cereb Cortex 27:5683-5695
Levman, Jacob; MacDonald, Patrick; Lim, Ashley Ruyan et al. (2017) A pediatric structural MRI analysis of healthy brain development from newborns to young adults. Hum Brain Mapp 38:5931-5942
Charvet, Christine J; Hof, Patrick R; Raghanti, Mary Ann et al. (2017) Combining diffusion magnetic resonance tractography with stereology highlights increased cross-cortical integration in primates. J Comp Neurol 525:1075-1093
Charvet, Christine J; Šimi?, Goran; Kostovi?, Ivica et al. (2017) Coevolution in the timing of GABAergic and pyramidal neuron maturation in primates. Proc Biol Sci 284:
Wilkinson, Molly; Lim, Ashley R; Cohen, Andrew H et al. (2017) Detection and Growth Pattern of Arcuate Fasciculus from Newborn to Adult. Front Neurosci 11:389
Vasung, Lana; Raguz, Marina; Kostovic, Ivica et al. (2017) Spatiotemporal Relationship of Brain Pathways during Human Fetal Development Using High-Angular Resolution Diffusion MR Imaging and Histology. Front Neurosci 11:348

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