Global gray and white matter metabolic changes after simian immunodeficiency virus infection in CD8-depleted rhesus macaques: Proton MRS imaging at 3 T

To test the hypotheses that global decreased neuro-axonal integrity reflected by decreased N-acetylaspartate (NAA) and increased glial activation reflected by an elevation in its marker, the myo-inositol (mI), present in a CD8-depleted rhesus macaque model of HIV-associated neurocognitive disorders. To this end, we performed quantitative MRI and 16×16×4 multivoxel proton MRS imaging (TE/TR=33/1400ms) in five macaques pre- and 4-6weeks post-simian immunodeficiency virus infection. Absolute NAA, creatine, choline (Cho), and mI concentrations, gray and white matter (GM and WM) and cerebrospinal fluid fractions were obtained. Global GM and WM concentrations were estimated from 224 voxels (at 0.125cm³ spatial resolution over ~35% of the brain) using linear regression. Pre- to post-infection global WM NAA declined 8%: 6.6±0.4 to 6.0±0.5mM (p=0.05); GM Cho declined 20%: 1.3±0.2 to 1.0±0.1mM (p<0.003); global mI increased 11%: 5.7±0.4 to 6.5±0.5mM (p<0.03). Global GM and WM brain volume fraction changes were statistically insignificant. These metabolic changes are consistent with global WM (axonal) injury and glial activation, and suggest a possible GM host immune response.