Background:  Blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) can assess the impact of HIV in the brain. Recently developed quantitative fMRI extends these principles by simultaneously acquiring BOLD and changes in cerebral blood flow (ΔCBF) during functional activation and hypercapnia experiments in order to determine changes in cerebral metabolic rate of oxygen consumption (ΔCMRO₂). We hypothesized that HIV⁺ patients had elevated functional changes in ΔCBF and ΔCMRO₂ due to impairments in presynaptic glutamate recycling.

Methods:  We studied at 3 T 12 HIV⁺ neurocognitively normal patients (global deficit scale < 0.20) and 12 age-matched seronegative controls. All subjects viewed numbers in the center of a screen flickering at 2 Hz, which corresponded to finger taps on a 4-button box. A region-of-interest corresponding to the lenticular nuclei was chosen because it is involved in this task and is also commonly affected by virus. Paired t-tests for BOLD, ΔCBF, and ΔCMRO₂ were performed with p values significant if p <0.05. In addition, correlation coefficients were obtained between these quantitative measures and log plasma and cerebral spinal fluid (CSF) HIV viral loads.

Results:  HIV⁺ patients were predominantly male (75%), more than half (67%) were on ART with many having undectectable viral loads (75%). Median CD4 at time of imaging was 482 (IQR 325 to 560) with most having good virological control within the plasma (log plasma viral load 2.56 (1.69 to 2.85) and CSF (log CSF viral load 2.12 (1.69 to 2.91)). Surprisingly, there was no significant differences in the BOLD responses between these 2 groups. However, both ΔCBF and ΔCMRO₂  responses were significantly greater for HIV⁺ patients. No significant correlation was observed between ΔCBF and ΔCMRO₂ values and log plasma or CSF HIV RNA loads.

Conclusions:  Quantitative fMRI demonstrates significant differences in ΔCBF and ΔCMRO₂ between neuropsychologically unimpaired HIV⁺ patients and seronegative controls that are not seen with BOLD fMRI alone. These differences may reflect relative impairments in presynaptic recycling of glutamate. Observed differences do not correlate with existing markers of HIV disease and could reflect ongoing inflammation and oxidative stress even in unimpaired HIV⁺ subjects with good virologic control on ART.