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Reliability of White Matter Microstructural Changes in HIV Infection: Meta-Analysis and Confirmation
E E O'Connor1, A Jaillard2,3, F Renard2,3
1From the Department of Radiology and Nuclear Medicine (E.E.O.), University of Maryland Medical System, Baltimore, Maryland erin.oconnor@umm.edu.
Background:
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 then examine the DTI reliability in a longitudinal seropositive cohort.
Data Sources:
Published studies and investigators.
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.
Data Synthesis:
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.
Limitations:
Many studies pooled participants with varying treatments, ages, and disease durations.
Conclusions:
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.
Insights
Diffusion tensor imaging (DTI) shows HIV impacts white matter microstructure, but results vary. DTI measures are reliable over time in HIV patients, suggesting potential as disease markers.
Area of Science:
- Neuroimaging
- Biomedical Engineering
- Infectious Diseases
Background:
- Diffusion tensor imaging (DTI) is crucial for assessing HIV-related white matter changes.
- Previous studies show inconsistencies in DTI measures like fractional anisotropy and mean diffusivity in HIV patients.
Purpose of the Study:
- Evaluate consistency of HIV effects on DTI measures across studies.
- Assess the reliability of DTI in a longitudinal cohort of HIV-positive individuals.
Main Methods:
- Conducted a meta-analysis of 16 cross-sectional studies for fractional anisotropy and 12 for mean diffusivity.
- Estimated DTI longitudinal reliability in HIV-positive participants over 6 months of treatment.
Main Results:
- Meta-analysis indicated lower fractional anisotropy and higher mean diffusivity in HIV patients, with significant heterogeneity.
- Longitudinal data showed higher fractional anisotropy and lower mean diffusivity, with high stability (ICC >0.96) over 6 months.
Conclusions:
- Substantial variations in reported HIV effects on white matter microstructure exist.
- Controlled DTI acquisition and processing yield reliable, stable measures.
- DTI's high longitudinal reliability makes it a promising marker for HIV disease activity.
