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.
KeywordsHIV Multi-site Harmonization TDF Diffusion MRI ComBat DTI
Funding for ENIGMA is provided as part of the BD2K Initiative U54 EB020403 to support big data analytics, and by P41 EB015922. Work from each site was funded by: (1) UCLA: K23MH095661, Clinical and Translational Research Center Grants UL1RR033176 and UL1TR000124 (ADT); MH19535 (TK); (2) Serbia: Provincial Secretariat for Higher Education and Scientific Research 114-451-2730/2016-02; (3) UNSW: NHMRC APP568746 (LC); (4) Brown and ARCH: R01MH074368, the Lifespan/Tufts/Brown Center for AIDS Research P30 AI042853, P01AA019072 (RC); (5) UCSF: K23AG032872 (VV), R01AG048234, and R01AG032289; (6) Resilience: R01MH102151 (JA). This work was also supported by R01MH085604 Neuropathogenesis of clade C HIV in South Africa.
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