Abstract
Diffusion tensor imaging has been widely used to measure HIV effects on white matter microarchitecture. While many authors have reported reduced fractional anisotropy and increased mean diffusivity in HIV, quantitative inconsistencies across studies are numerous. Our aim was to evaluate the consistency across studies of HIV effects on DTI measures and then examine the DTI reliability in a longitudinal seropositive cohort. Published studies and investigators. The meta-analysis included 16 cross-sectional studies reporting fractional anisotropy and 12 studies reporting mean diffusivity in the corpus callosum. Random-effects meta-analysis was used to estimate study standardized mean differences and heterogeneity. DTI longitudinal reliability was estimated in seropositive participants studied before and 3 and 6 months after beginning treatment. Meta-analysis revealed lower fractional anisotropy (standardized mean difference, -0.43; P < .001) and higher mean diffusivity (standardized mean difference, 0.44; P < .003) in seropositive participants. Nevertheless, between-study heterogeneity accounted for 58% and 66% of the observed variance (P < .01). In contrast, the longitudinal cohort fractional anisotropy was higher and mean diffusivity was lower in seropositive participants (both, P < .001), and fractional anisotropy and mean diffusivity measures were very stable during 6 months, with intraclass correlation coefficients all >0.96. Many studies pooled participants with varying treatments, ages, and disease durations. HIV effects on WM microstructure had substantial variations that could result from acquisition, processing, or cohort-selection differences. When acquisition parameters and processing were carefully controlled, the resulting DTI measures did not show high temporal variation. HIV effects on WM microstructure may be age-dependent. The high longitudinal reliability of DTI WM microstructure measures makes them promising disease-activity markers.
Highlights
Diffusion tensor imaging has been widely used to measure HIV effects on white matter microarchitecture
HIV effects on WM microstructure had substantial variations that could result from acquisition, processing, or cohortselection differences
The remaining studies were excluded for the following reasons: 1) Numeric values for fractional anisotropy (FA) and mean diffusivity (MD) were not reported for either seropositive or seronegative participants; 2) only whole-brain FA or MD was reported; 3) the studies examined the relationships of clinical variables, biomarkers, or treatment on DTI measures without including a seronegative control group; 4) FA and MD were not measured in the corpus callosum; 5) prior published DTI data were used for fMRI connectivity analysis ROI selection; 6) a single case-control pair was reported; 7) the study focused on imaging measures other than diffusion parameters; or 8) the article reported a new processing algorithm for DTI data (Fig 1)
Summary
Diffusion tensor imaging has been widely used to measure HIV effects on white matter microarchitecture. While many authors have reported reduced fractional anisotropy and increased mean diffusivity in HIV, quantitative inconsistencies across studies are numerous. PURPOSE: Our aim was to evaluate the consistency across studies of HIV effects on DTI measures and examine the DTI reliability in a longitudinal seropositive cohort. STUDY SELECTION: The meta-analysis included 16 cross-sectional studies reporting fractional anisotropy and 12 studies reporting mean diffusivity in the corpus callosum. DATA ANALYSIS: Random-effects meta-analysis was used to estimate study standardized mean differences and heterogeneity. DTI longitudinal reliability was estimated in seropositive participants studied before and 3 and 6 months after beginning treatment
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