Relationships between Astrogliosis and 1H MR Spectroscopic Measures of Brain Choline/Creatine and Myo-Inositol/Creatine in a Primate Model
John P. Kima,
Margaret R. Lentza,
Susan V. Westmorelandb,
Jane B. Grecoa,
Eva M. Rataia,
Elkan Halperna,
Andrew A. Lacknerc,
Eliezer Masliahd and
R. Gilberto Gonzáleza
a Massachusetts General Hospital, A.A. Martinos Center for Biomedical Imaging and Neuroradiology Division, Charlestown
b New England Primate Research Center, Southborough, MA
c Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, LA
d Department of Neurosciences, University of California, San Diego, La Jolla
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FIG 1. Serum SIV load in rhesus macaque blood during acute infection. Data are from 11 animals used in postmortem examinations. Error bars = SEM.
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FIG 2. Changes in GFAP immunostaining and in vivo Cho/Cr and MI/Cr after SIV infection. Levels of GFAP were determined by immunohistochemistry. Levels of Cho/Cr and MI/Cr are from 1H MR spectroscopic measurements previously reported (1). Peaks of all three measures were attained at 11–12 days, coincident with peak viremia. Measures then diverge, with GFAP immunostains returning to normal levels by 14 dpi (DPI), MI/Cr remaining elevated, and Cho/Cr decreasing to subnormal levels at 25–27 dpi. Error bars = SEM.
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FIG 3. Correlation between frontal cortex GFAP immunostains and plasma viral load was significant (Spearman rank correlation coefficient Rs = 0.64, P < .05).
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FIG 4. In vivo spectrum of control frontal cortex was obtained at 1.5 T (top) and collected with PROBE-P (11) (point-resolved [PRESS] sequence with chemical shift selective [CHESS] water suppression [12, 13], TR/TE/NEX = 3000/35/128). The animal was euthanized, a frontal cortex sample was removed, and metabolites were extracted for ex vivo high-resolution 1H MR study at 14.1 T (bottom). Gln = glutamine, Glu = glutamate, GPC = glycerophosphorylcholine, PC = phosphorylcholine, tau = taurine.
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FIG 5. Expanded high-resolution ex vivo 1H MR spectrum of control frontal cortex extract improves delineation of the complex contributions of several water-soluble metabolites designated as MI and Cho on 1.5-T in vivo 1H MR spectra. Gln = glutamine, Glu = glutamate, GPC = glycerophosphorylcholine, PC = phosphorylcholine, s-Ino = scyllo-inositol, tau = taurine.
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FIG 6. Comparison of Cho/Cr and MI/Cr in vivo and ex vivo in the frontal cortex after SIV infection. Time course of Cho/Cr in vivo differs from Cho/Cr ex vivo. One possible explanation is that significant changes in the macromolecular contributions to the in vivo MR spectrum occur during infection and that extraction procedure removes these. Differences between in vivo and ex vivo MI/Cr are also apparent although not as dramatic. In vivo data were previously reported (1). Error bars = SEM.
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