Effects of Diffusion MRI Model and Harmonization on the Consistency of Findings in an International Multi-cohort HIV Neuroimaging Study

HIV-related white matter (WM) differences reported across studies are inconsistent. This is due to clinical and demographic heterogeneity of HIV infected populations, and variations in diffusion MRI (dMRI) acquisition, processing, and analysis methods across studies. Therefore, reliable neuroanatomical consequences of infection and therapeutic targets are difficult to identify. Here, we pooled data from six existing HIV studies from around the world as part of the ENIGMA-HIV consortium to evaluate (1) the effects of harmonization of dMRI measures across sites using ComBat, and (2) whether an improved, higher-order tensor dMRI model, the tensor distribution function (TDF), and derived scalar index (FATDF) conferred higher sensitivity across heterogeneous sites to understand the effect of HIV on WM microstructure. This study suggests that improved dMRI indices and harmonization of these measures across cohorts, may be helpful for detecting consistent effects of disease on the brain in international multi-site studies, while preserving biological differences.