Abstract
BackgroundIn vivo proton magnetic resonance spectroscopy (1H-MRS) studies of HIV-infected humans have demonstrated significant metabolic abnormalities that vary by brain region, but the causes are poorly understood. Metabolic changes in the frontal cortex, basal ganglia and white matter in 18 SIV-infected macaques were investigated using MRS during the first month of infection.ResultsChanges in the N-acetylaspartate (NAA), choline (Cho), myo-inositol (MI), creatine (Cr) and glutamine/glutamate (Glx) resonances were quantified both in absolute terms and relative to the creatine resonance. Most abnormalities were observed at the time of peak viremia, 2 weeks post infection (wpi). At that time point, significant decreases in NAA and NAA/Cr, reflecting neuronal injury, were observed only in the frontal cortex. Cr was significantly elevated only in the white matter. Changes in Cho and Cho/Cr were similar across the brain regions, increasing at 2 wpi, and falling below baseline levels at 4 wpi. MI and MI/Cr levels were increased across all brain regions.ConclusionThese data best support the hypothesis that different brain regions have variable intrinsic vulnerabilities to neuronal injury caused by the AIDS virus.
Highlights
In vivo proton magnetic resonance spectroscopy (1H-MRS) studies of HIV-infected humans have demonstrated significant metabolic abnormalities that vary by brain region, but the causes are poorly understood
To help understand brain region specific variations in HIV/AIDS, we evaluated the neurochemical changes observed by in vivo 1H MRS in the basal ganglia and white matter, and compared them to the changes seen in the frontal cortex in 18 simian immunodeficiency virus (SIV)-infected rhesus macaques
A total of 18 rhesus macaques were infected with SIV, and imaged with in vivo 1H MRS at multiple time points including pre-infection and up to 4 weeks after infection. 1H MR spectra were separately acquired from 3 specific brain regions, frontal cortex, basal ganglia, and centrum semiovale, as illustrated in Figure 1. 1H MR spectra with short echo time (TE = 35 ms) are characterized by resonances primarily arising from NAA, MI, Cr, Cho, and Glx (Figure 1)
Summary
In vivo proton magnetic resonance spectroscopy (1H-MRS) studies of HIV-infected humans have demonstrated significant metabolic abnormalities that vary by brain region, but the causes are poorly understood. Metabolic changes in the frontal cortex, basal ganglia and white matter in 18 SIV-infected macaques were investigated using MRS during the first month of infection. In vivo 1H MRS studies of chronically HIV infected patients have disclosed varying metabolic abnormalities in different brain regions [5,6]. In vivo macaque brain 1H MR spectra are similar to humans and post mortem and in vivo MRS studies from SIV infected macaques have revealed metabolic abnormalities [13,14,15] similar to those observed in HIV-infected human brains by in vivo MRS [16,17]. A power calculation conducted by Greco et al revealed that single voxel MRS at 1.5 Tesla was capable of detecting changes similar to those observed in human MRS studies for most metabolites using less than 10 animals [18]
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