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

Abstract

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% CO(2)) 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 (CMRO(2)) 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 CMRO(2) 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 CMRO(2) (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 CMRO(2) with disease.

Figure 1

Time series of functional changes in cerebral blood flow (A) and blood oxygen level dependent (BOLD) responses for a representative seronegative (HIV−) control and HIV infected (HIV+) patient at the two sessions.

Figure 2

Spaghetti plots of natural logarithm transformed calibrated blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) measures for seronegative (HIV−) controls and HIV infected (HIV+) patients at both 1^st and 2^nd scans. There were no systematic changes in a) baseline cerebral blood flow (CBF) b) functional BOLD c) functional CBF changes or d) functional cerebral metabolic rate of oxygen consumption (CMRO₂) between scanning sessions for each group.