Data using SPECT brain imaging in HIV infection suggest that decreased cerebral blood flow occurs early in disease course, with more extensive abnormalities associated with disease progression. Data also suggest that disease progression is associated with decreased relative frontal perfusion and relative increases in parietal regional perfusion. The pattern of hypofrontal perfusion correlates with, and may be mediated by, subcortical structural abnormalities. Specifically, the volume of abnormal white matter is correlated negatively with decreased frontal and temporal perfusion. In addition, there is a suggestion that abnormalities of lenticular volume and subcortical abnormal white matter correlate with frontal and parietal perfusion abnormalities. Preliminary data from acetazolamide activation studies indicate that vascular response to a vasodilatory stimulus is abnormal in HIV infection. Using longitudinal follow-up of SPECT scans in resting, cognitive and acetazolamide stimulated condition, the proposed study will attempt to further define the cognitive, clinical and pathophysiologic significance of blood flow abnormalities in HIV infection. It is predicted that a pattern of hypofrontal blood flow will worsen over time, and that tracer injection during the performance of a cognitive activation task will demonstrate failure to activate frontal and posterior temporal regions in the HIV positive subjects. Finally, it is hypothesized that HIV-infected persons will demonstrate blunted response to acetazolamide, reflecting abnormalities in cerebrovascular responsiveness mediated by HIV. The proposed study incorporates plans for image analysis using MR-SPECT registration, and will focus on the relationship between subcortical and cortical functional disturbance related to HIV infection.
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