TY - JOUR
T1 - Miniature pig model of human adolescent brain white matter development
AU - Ryan, Meghann C.
AU - Sherman, Paul
AU - Rowland, Laura M.
AU - Wijtenburg, S. Andrea
AU - Acheson, Ashley
AU - Fieremans, Els
AU - Veraart, Jelle
AU - Novikov, Dmitry S.
AU - Hong, L. Elliot
AU - Sladky, John
AU - Peralta, P. Dana
AU - Kochunov, Peter
AU - McGuire, Stephen A.
N1 - Funding Information:
This work was supported by U.S. Air Force Surgeon General I-11-10 and I-11-44 711HPW FA8650-10- d -6052 0048. This work was also supported by NIH grants: R01EB015611 , R01MH094520 , R01MH096263 and P50 MH103222 .
Funding Information:
This work was supported by U.S. Air Force Surgeon General I-11-10 and I-11-44 711HPW FA8650-10- d -6052 0048 .
PY - 2018/2/15
Y1 - 2018/2/15
N2 - 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.
AB - 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.
KW - Adolescent brain development
KW - Diffusion weighted imaging
KW - Miniature swine
KW - White matter
UR - http://www.scopus.com/inward/record.url?scp=85040083904&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040083904&partnerID=8YFLogxK
U2 - 10.1016/j.jneumeth.2017.12.017
DO - 10.1016/j.jneumeth.2017.12.017
M3 - Article
C2 - 29277719
AN - SCOPUS:85040083904
VL - 296
SP - 99
EP - 108
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
SN - 0165-0270
ER -