Meghann C Ryan1, Peter Kochunov2, Paul M Sherman3, Laura M Rowland4, S Andrea Wijtenburg5, Ashley Acheson6, L Elliot Hong7, John Sladky8, Stephen McGuire9. 1. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, 55 Wade Avenue, Catonsville, MD 21228, United States. Electronic address: mcryan@som.umaryland.edu. 2. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, 55 Wade Avenue, Catonsville, MD 21228, United States. Electronic address: pkochunov@som.umaryland.edu. 3. 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 Radiology, 59thMedical Wing, 1100 Wilford Hall Loop, Bldg 4551, Joint Base San Antonio, TX, 78236, United States. Electronic address: paul.m.sherman3.civ@mail.mil. 4. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, 55 Wade Avenue, Catonsville, MD 21228, United States. Electronic address: Lrowland@som.umaryland.edu. 5. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, 55 Wade Avenue, Catonsville, MD 21228, United States. Electronic address: AWijtenburg@som.umaryland.edu. 6. Department of Psychiatry, University of Arkansas for Medical Sciences, 4301 W Markham St., Little Rock, AR, 72205, United States. Electronic address: AWAcheson@uams.edu. 7. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, 55 Wade Avenue, Catonsville, MD 21228, United States. Electronic address: ehong@som.umaryland.edu. 8. 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, 1100 Wilford Hall Loop, Bldg 4551, Joint Base San Antonio, Lackland AFB, TX, 78236, United States. Electronic address: john.h.sladky.mil@mail.mil. 9. Department of Neurology, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, United States. Electronic address: dr.stephen.mcguire@gmail.com.
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.
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.
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