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A Versatile Murine Model of Subcortical White Matter Stroke for the Study of Axonal Degeneration and White Matter Neurobiology
Published on: March 17, 2016
Miniature pig model of human adolescent brain white matter development
Meghann C Ryan1, Paul Sherman2, Laura M Rowland1
1Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, 55 Wade Avenue, Catonsville, MD 21228, United States.
Insights
Miniature pigs provide a valuable in vivo model for studying brain development, showing significant white matter changes during maturation. This research aids in understanding human brain development and disorders using advanced MRI techniques.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Neuroimaging
Background:
- Developing an in vivo animal model for neuroscience research is crucial for studying brain development and disorders.
- A suitable model requires a large cerebrum for human MRI compatibility and should reflect normal white matter (WM) development.
- Current models may not fully meet these criteria, necessitating alternative approaches.
Purpose of the Study:
- To evaluate Sinclair™ miniature pigs as an in vivo model for adolescent cerebral white matter development.
- To longitudinally assess white matter maturation using advanced diffusion-weighted imaging (DWI) techniques.
- To compare pig brain development trajectories with human patterns.
Main Methods:
- Twelve 3-month-old miniature pigs underwent three MRI scans during adolescent development.
- Advanced DWI protocols, mirroring human techniques, were employed using a 3-T scanner.
- Diffusion kurtosis and bi-exponential modeling analyzed data, yielding metrics like fractional anisotropy (FA) and permeability-diffusivity index (PDI).
Main Results:
- Significant longitudinal changes were observed in whole-brain average FA, kurtosis anisotropy (KA), and PDI (p < 0.001).
- Regional variations in developmental trends were noted, with the corpus callosum exhibiting the most rapid changes.
- These findings indicate ongoing myelination and maturation of cerebral white matter.
Conclusions:
- Miniature pigs possess large, gyrencephalic brains suitable for clinical MRI studies.
- The observed diffusion changes reflect normal white matter maturation, mirroring human development.
- Pigs offer a viable alternative to non-human primates in neuroscience research, aligning with ethical principles.
Background:
Neuroscience research in brain development and disorders can benefit from an in vivo animal model that portrays normal white matter (WM) development trajectories and has a sufficiently large cerebrum for imaging with human MRI scanners and protocols.
New Method:
Twelve three-month-old Sinclair™ miniature pigs (Sus scrofa domestica) were longitudinally evaluated during adolescent development using advanced diffusion weighted imaging (DWI) focused on cerebral WM. Animals had three MRI scans every 23.95 ± 3.73 days using a 3-T scanner. The DWI imaging protocol closely modeled advanced human structural protocols and consisted of fifteen b-shells (b = 0-3500 s/mm2) with 32-directions/shell. DWI data were analyzed using diffusion kurtosis and bi-exponential modeling that provided measurements that included fractional anisotropy (FA), radial kurtosis, kurtosis anisotropy (KA), axial kurtosis, tortuosity, and permeability-diffusivity index (PDI).
Results:
Significant longitudinal effects of brain development were observed for whole-brain average FA, KA, and PDI (all p < 0.001). There were expected regional differences in trends, with corpus callosum fibers showing the highest rate of change.
Comparison With Existing Method(S):
Pigs have a large, gyrencephalic brain that can be studied using clinical MRI scanners/protocols. Pigs are less complex than non-human primates thus satisfying the "replacement" principle of animal research.
Conclusions:
Longitudinal effects were observed for whole-brain and regional diffusion measurements. The changes in diffusion measurements were interepreted as evidence for ongoing myelination and maturation of cerebral WM. Corpus callosum and superficial cortical WM showed the expected higher rates of change, mirroring results in humans.
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