Fixel-Based Analysis and Free Water Corrected DTI Evaluation of HIV Associated Neurocognitive Disorders

White matter damage is a consistent finding in HIV infected (HIV+) individuals. Previous studies have evaluated WM fiber tract specific brain regions in HIV-associated neurocognitive disorders using diffusion tensor imaging (DTI). However, DTI might lack an accurate biological interpretation, and the technique suffers from several limitations. Here, we sought to evaluate Fixel-based analysis (FBA) and free water corrected DTI (fwcDTI) metrics between HIV+ and HIV uninfected (HIV-) individuals, and their relationships with blood markers and cognitive scores. We also compared the specificity of both MRI metrics in their ability to distinguish between individuals with and without cognitive impairment using machine learning classifiers. Using 94 age-matched participants, we found that whole brain FBA was significantly reduced (up to 15%) in various fiber bundles. Tract based special statistics (TBSS) of fwcDTI metrics revealed decreased fractional anisotropy FAT (by 1-2%) in HIV+ compared to HIV- individuals in areas consistent with those observed in FBA, but these were not significant. An adaptive boosting classifier reliably distinguished between cognitively normal patients and those with cognitive impairment with 80% precision and 78% recall. Therefore, FBA may serve as a potential in-vivo biomarker for evaluating and monitoring axonal degeneration in HIV+ patients at risk for neurocognitive impairment.