Test-retest stability of calibrated BOLD-fMRI in HIV− and HIV+ subjects

Subject performance, scanner hardware, or biological factors can affect single session neuroimaging measures. Stability studies using calibrated blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) have been performed in health but not disease. We utilized calibrated BOLD-fMRI to determine the effects of HIV on neurovascular coupling. Six clinically stable HIV-infected patients (HIV+) and 10 seronegative controls (HIV−) were scanned at two separate sessions approximately 3 months apart. Both mild hypercapnia (5% CO2) exposure and a visual functional activation task were performed. Intraclass correlation coefficients (ICC) and inter-subject variance were determined for calibrated BOLD-fMRI measures (baseline cerebral blood flow (CBF), functional CBF, BOLD, and cerebral metabolic rate of oxygen consumption (CMRO2) changes) for HIV+ and HIV− subjects. The two groups did not differ in age, sex, or education. HIV+ subjects had lower mean baseline CBF (p < 0.04, Cohen's d = −1.07) and functional BOLD responses (p < 0.001, Cohen's d = −2.47) and a trend towards a decrease in mean functional CBF responses (p = 0.07, Cohen's d = −0.92) despite similar mean functional CMRO2 changes (p = 0.71, Cohen's d = 0.19). The stability of each calibrated BOLD-fMRI measure, as assessed by ICC, was significantly lower for HIV+ subjects. In addition, HIV+ participants had greater inter-subject variability for baseline CBF (p < 0.02), functional BOLD (p < 0.001), CBF (p < 0.001), and CMRO2 (p < 0.002) responses. Our results demonstrate that calibrated BOLD-fMRI measures have excellent stability within healthy controls. In contrast, these values have greater variability in clinically stable HIV+ subjects and may reflect alterations in coupling between CBF and CMRO2 with disease.

Research Highlights►Compared to HIV− subjects, HIV+ subjects have (a) lower mean baseline CBF (p < 0.04, Cohen's d = −1.07), (b) functional BOLD responses (p < 0.001, Cohen's d = −2.47), (c) trends towards a decrease in mean functional CBF responses (p = 0.07, Cohen's d = −0.92), (d) similar mean functional CMRO2 changes (p = 0.71, Cohen's d = 0.19). ►The stability of each calibrated BOLD-fMRI measure was significantly lower for HIV+ subjects compared to HIV− subjects. ►HIV+ participants have greater inter-subject variability for calibrated BOLD measurements.