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Structural and Diffusion MRI Analyses With Histological Observations in Patients With Lissencephaly
Lana Vasung1,2, Arthur Rezayev1,2, Hyuk Jin Yun1,2
1Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States.
Frontiers in Cell and Developmental Biology
|July 30, 2019
Summary
Lissencephaly, a brain development disorder, shows that the cerebral cortex is more affected than the subcortical structures. This study used MRI and histology to examine brain development in lissencephaly patients.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Cortical convolutions (gyri and sulci) form during prenatal development.
- Lissencephaly, a rare genetic disorder, presents as a smooth brain lacking convolutions, offering insights into cortical development.
- Understanding the biological processes behind gyration is crucial for developmental neuroscience.
Purpose of the Study:
- To investigate the microstructural and macrostructural differences in the brains of individuals with lissencephaly compared to controls.
- To identify the impact of lissencephaly on white and gray matter, particularly cortical versus subcortical structures.
- To explore the relationship between specific genetic mutations (LIS1, DCX) and the pattern of cortical malformation.
Main Methods:
- Retrospective analysis of structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) in 10 patients with lissencephaly and 10 controls.
- Histological examination of postmortem brains from 4 patients with lissencephaly and 4 age-matched controls.
- Quantitative assessment of gyrification index and regional brain volumes.
Main Results:
- Patients with lissencephaly exhibited a significantly reduced gyrification index and smaller hemispheric white and gray matter volumes compared to controls.
- Subcortical gray matter volumes did not significantly differ between groups.
- While major fissures were often preserved, the spatial distribution of agyric regions varied with LIS1 and DCX mutations. Projection pathways remained intact, but short- to medium-range cortico-cortical pathways were diminished.
Conclusions:
- Lissencephaly primarily affects the cortical system over the subcortical system.
- The study highlights distinct patterns of malformation based on underlying genetic mutations.
- These findings advance the understanding of brain development and the pathogenesis of cortical malformations.
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