TY - JOUR
T1 - Miniature pig magnetic resonance spectroscopy model of normal adolescent brain development
AU - Ryan, Meghann C.
AU - Kochunov, Peter
AU - Sherman, Paul M.
AU - Rowland, Laura M.
AU - Wijtenburg, S. Andrea
AU - Acheson, Ashley
AU - Hong, L. Elliot
AU - Sladky, John
AU - McGuire, Stephen
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 ; NIH grants: R01EB015611 , R01MH094520 , R01MH096263 , R21MH113182 , and P50 MH103222 ; and the Arkansas Biosciences Institute .
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - Background: We are developing the miniature pig (Sus scrofa domestica), an in-vivo translational, gyrencephalic model for brain development, as an alternative to laboratory rodents/non-human primates. We analyzed longitudinal changes in adolescent pigs using proton magnetic resonance spectroscopy (1H-MRS) and examined the relationship with white matter (WM) integrity derived from diffusion weighted imaging (DWI). New method: Twelve female Sinclair™ pigs underwent three imaging/spectroscopy sessions every 23.95 ± 3.73 days beginning at three months of age using a clinical 3 T scanner. 1H-MRS data were collected using 1.2 × 1.0 × 3.0 cm voxels placed in left and right hemisphere WM using a Point Resolved Spectroscopy sequence (TR = 2000 ms, TE = 30 ms). Concentrations of N-acetylaspartate, myo-inositol (MI), glutamate + glutamine, choline, creatine, and macromolecules (MM) 09 and 14 were averaged from both hemispheres. DWI data were collected using 15 shells of b-values (b = 0–3500 s/mm2) with 32 directions/shell and fit using the WM Tract Integrity model to calculate fractional anisotropy (FA), kurtosis anisotropy (KA) and permeability-diffusivity index. Results: MI and MM09 significantly declined with age. Increased FA and KA significantly correlated with decline in MI and MM09. Correlations lost significance once corrected for age. Comparison with existing methods: MRI scanners/protocols can be used to collect 1H-MRS and DWI data in pigs. Pigs have a larger, more complex, gyrencephalic brain than laboratory rodents but are less complex than non-human primates, thus satisfying the “replacement” principle of animal research. Conclusions: Longitudinal effects in MRS measurements were similar to those reported in adolescent humans. MRS changes correlated with diffusion measurements indicating ongoing WM myelination/maturation.
AB - Background: We are developing the miniature pig (Sus scrofa domestica), an in-vivo translational, gyrencephalic model for brain development, as an alternative to laboratory rodents/non-human primates. We analyzed longitudinal changes in adolescent pigs using proton magnetic resonance spectroscopy (1H-MRS) and examined the relationship with white matter (WM) integrity derived from diffusion weighted imaging (DWI). New method: Twelve female Sinclair™ pigs underwent three imaging/spectroscopy sessions every 23.95 ± 3.73 days beginning at three months of age using a clinical 3 T scanner. 1H-MRS data were collected using 1.2 × 1.0 × 3.0 cm voxels placed in left and right hemisphere WM using a Point Resolved Spectroscopy sequence (TR = 2000 ms, TE = 30 ms). Concentrations of N-acetylaspartate, myo-inositol (MI), glutamate + glutamine, choline, creatine, and macromolecules (MM) 09 and 14 were averaged from both hemispheres. DWI data were collected using 15 shells of b-values (b = 0–3500 s/mm2) with 32 directions/shell and fit using the WM Tract Integrity model to calculate fractional anisotropy (FA), kurtosis anisotropy (KA) and permeability-diffusivity index. Results: MI and MM09 significantly declined with age. Increased FA and KA significantly correlated with decline in MI and MM09. Correlations lost significance once corrected for age. Comparison with existing methods: MRI scanners/protocols can be used to collect 1H-MRS and DWI data in pigs. Pigs have a larger, more complex, gyrencephalic brain than laboratory rodents but are less complex than non-human primates, thus satisfying the “replacement” principle of animal research. Conclusions: Longitudinal effects in MRS measurements were similar to those reported in adolescent humans. MRS changes correlated with diffusion measurements indicating ongoing WM myelination/maturation.
KW - Adolescent brain development
KW - Diffusion weighted imaging
KW - Magnetic resonance spectroscopy
KW - Miniature pigs
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U2 - 10.1016/j.jneumeth.2018.08.008
DO - 10.1016/j.jneumeth.2018.08.008
M3 - Article
C2 - 30099002
AN - SCOPUS:85051394433
VL - 308
SP - 173
EP - 182
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
SN - 0165-0270
ER -