Relationships between Astrogliosis and ¹H MR Spectroscopic Measures of Brain Choline/Creatine and Myo-Inositol/Creatine in a Primate Model

Abstract

BACKGROUND AND PURPOSE: In vivo¹H MR spectroscopy demonstrates elevated choline (Cho)/creatine (Cr) and myo-inositol (MI)/Cr in many neurologic diseases that has been ascribed to gliosis. We tested the hypotheses that in vivo Cho/Cr and/or MI/Cr levels are correlated with glial fibrillary acidic protein (GFAP) immunostains and that the changes are water-soluble metabolites.

METHODS: We performed postmortem ¹H MR spectroscopy and GFAP immunohistochemistry in brains from seven rhesus macaques acutely infected with simian immunodeficiency virus (SIV) and in four controls and compared the findings with previous in vivo MR spectroscopic results. Changes in neuropathologic and MR spectroscopic markers after infection and relationships among plasma viral load, GFAP immunostaining results, and ex vivo and in vivo MR spectroscopic measures were statistically evaluated.

RESULTS: On GFAP immunostaining and in vivo MR spectroscopy, GFAP, Cho/Cr and MI/Cr were highest near the time of peak plasma viral load at 11 days postinfection (dpi). Immunostains returned to baseline by 14 dpi, whereas Cho/Cr and MI/Cr had different time courses, with the former dropping below baseline and the latter remaining elevated. Viral load and immunostains were significantly correlated. No correlation was found between ex vivo Cho/Cr or MI/Cr and viral load or between metabolite ratios from in vivo and ex vivo MR spectroscopy.

CONCLUSION: In acute SIV infection, plasma viral load was significantly correlated with brain GFAP immunostains and in vivo ¹H MR spectroscopic Cho/Cr. In vivo changes in Cho/Cr and MI/Cr were principally due to contributions other than those of low-molecular-weight water-soluble metabolites.