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Brain Pathways in LIS1-Associated Lissencephaly Revealed by Diffusion MRI Tractography
Alpen Ortug1,2, Briana Valli3, José Luis Alatorre Warren1,2
1Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA 02129, USA.
Brain Sciences
|December 23, 2023
Summary
Lissencephaly (LIS) causes abnormal brain development due to faulty neuronal migration. This study used diffusion MRI to reveal altered white matter fiber organization in LIS, impacting brain structure.
Area of Science:
- Neuroscience
- Developmental Biology
- Medical Imaging
Background:
- Lissencephaly (LIS) is a severe neurodevelopmental disorder characterized by abnormal neuronal migration during cortical development.
- While cortical abnormalities in LIS are studied, the impact on white matter structure remains less understood.
- LIS can result from genetic and non-genetic factors, with LIS1 gene mutations being a common cause.
Purpose of the Study:
- To investigate abnormal neuronal migration pathways and white matter fiber organization in LIS1-associated Lissencephaly.
- To utilize high-resolution ex vivo diffusion MRI (dMRI) tractography for detailed structural analysis.
- To compare white matter abnormalities in LIS specimens with age and sex-matched controls.
Main Methods:
- Acquisition of high-resolution ex vivo 3T dMRI data from brain specimens.
- Inclusion of three LIS specimens and four age and sex-matched control specimens.
- Application of dMRI tractography to analyze white matter fiber organization and neuronal migration pathways.
Main Results:
- Successful identification of common structural abnormalities in LIS specimens using dMRI.
- Observed an abnormal increase in radially oriented subcortical fibers, potentially linked to radial migration pathways and U-fibers.
- Detected a decrease in association fibers in all analyzed LIS specimens.
Conclusions:
- High-resolution ex vivo dMRI tractography is effective in characterizing white matter abnormalities in Lissencephaly.
- LIS is associated with significant alterations in white matter fiber organization, including increased radial and decreased association fibers.
- These findings contribute to a better understanding of the structural consequences of abnormal neuronal migration in LIS.
