Publication Abstract Display
Type: Published Abstract
Title: Cerebral blood flow and metabolism are increased in unimpaired HIV+ subjects.
Authors: Ances B, Jernigan T, Leontiev O, Perthen J, Liang C, Buxton R, Ellis R, and the HNRC Group
Year: 2007
Publication: 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, CA, February 26, 2007
Volume: Issue: Pages:
Abstract:Background: Blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) can noninvasively assess the effects of HIV in the brain. Quantitative fMRI extends these principles by simultaneously acquiring BOLD and cerebral blood flow (CBF) changes during functional activation and hypercapnia in order to determine cerebral metabolic rate of oxygen consumption (CMRO2), a closer approximation of synaptic transmission. We hypothesized that unimpaired HIV+ patients have elevated changes in CBF and CMRO2 due to derangements in presynaptic glutamate recycling within the lenticular nuclei (LN), a subcortical structure often affected by HIV. Methods: Seronegative controls (n=12) and HIV+ unimpaired patients (n= 12) were studied at 3 Tesla GE MRI scanner. All subjects viewed a fixed number pattern in the center of a screen which corresponded to finger taps on a 4-button box. The LN was manually drawn for each subject with clusters of active voxels chosen using an overall significance threshold of p = 0.05 (Figure 2). Paired t-tests for BOLD, !CBF, and !CMRO2 were performed with p values significant if p < 0.05. In addition, correlation coefficients were obtained between these quantitative fMRI measures and laboratory values (log plasma and cerebral spinal fluid (CSF) HIV viral loads and CD4 levels). Results: Unimpaired HIV+ patients were predominantly male (92%) with more than half (67%) taking antiretroviral (ARV) medications. Median CD4 at time of imaging was 446 (IQR 275-589) with most having good virological control within the plasma (log plasma viral load 2.79 (1.69-3.49) and CSF (log CSF viral load 1.89 (1.69-2.31) (Table 1). Functional changes in BOLD, CBF, and CMRO2 were significantly greater for unimpaired HIV+ patients compared to seronegative controls (Figure 3). No significant correlation existed between quantitative fMRI values and laboratory values (Figure 4). Conclusions: Quantitative fMRI demonstrates significant differences in functional changes in CBF , BOLD, and CMRO2 prior to neuropsychologically measured changes in HIV+ patients. These differences may reflect relative derangements in presynaptic recycling of glutamate in unimpaired HIV+ patients compared to controls. Observed differences do not correlate with existing laboratory markers of HIV disease and may reflect ongoing inflammation and oxidative stress even in unimpaired HIV+ subjects with good virologic control due to ARVs. Quantitative fMRI could assess the effects of early initiation of neuroprotective therapies for unimpaired HIV+ patients.

return to publications listing