Meghann C Ryan1, Paul Sherman2, Laura M Rowland1, S Andrea Wijtenburg1, Ashley Acheson3, Els Fieremans4, Jelle Veraart4, Dmitry S Novikov4, L Elliot Hong1, John Sladky5, P Dana Peralta6, Peter Kochunov7, Stephen A McGuire5. 1. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, 55 Wade Avenue, Catonsville, MD 21228, United States. 2. U.S. Air Force School of Aerospace Medicine, Aeromedical Research Department, 2510 5th Street, Building 840, Wright-Patterson AFB, OH 45433-7913, United States. 3. Department of Psychiatry, University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR 72205, United States. 4. Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, 660 1st Avenue, New York, NY 10016, United States. 5. U.S. Air Force School of Aerospace Medicine, Aeromedical Research Department, 2510 5th Street, Building 840, Wright-Patterson AFB, OH 45433-7913, United States; Department of Neurology, 59th Medical Wing, 2200 Bergquist Drive, Suite 1, Joint Base San Antonio-Lackland AFB, TX 78236, United States. 6. Department of Neurology, 59th Medical Wing, 2200 Bergquist Drive, Suite 1, Joint Base San Antonio-Lackland AFB, TX 78236, United States. 7. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, 55 Wade Avenue, Catonsville, MD 21228, United States. Electronic address: pkochunov@mprc.umaryland.edu.
Abstract
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.
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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