Miniature pig magnetic resonance spectroscopy model of normal adolescent brain development.
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ABSTRACT: 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.
SUBMITTER: Ryan MC
PROVIDER: S-EPMC6211793 | biostudies-literature | 2018 Oct
REPOSITORIES: biostudies-literature
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