Cerebral Multishell Diffusion Imaging Parameters are Associated with Blood Biomarkers of Disease Severity in HIV Infection

Abstract

Background and purpose: HIV-positive subjects suffer from neurocognitive deficits and disorder. We employ multishell diffusion imaging to investigate possible white matter microstructural correlates of infection severity, quantified through plasmatic percentage value of CD4 T-lymphocytes, Nadir-CD4 count, and plasma concentration of human immunodeficiency virus (HIV)-ribonucleic acid (RNA).

Methods: A total of 41 HIV patients underwent magnetic resonance imaging (MRI) and blood sampling to evaluate biochemical markers. Diffusion-weighted imaging was performed at 3 Tesla (b-values: 1000 s/mm² and 2500 s/mm², 64 gradient directions/b-value, 8 b0 images). The Diffusion Tensor Imaging and Diffusional Kurtosis Imaging models were fitted separately after which mean, radial, and axial diffusivity (MD, RD, AD, respectively), fractional anistrotropy (FA), mean and radial kurtosis (MK and RK, respectively), and kurtosis anisotropy (KA) maps were extracted. Associations of each metric with biochemical markers were explored through tract-based spatial statistics followed by threshold-free cluster enhancement.

Results: We found significant positive associations between Nadir-CD4 values and both KA and FA, and significant negative associations between Nadir-CD4 values and MD. Also, we found significant positive associations among %CD4 and MK, KA, and FA, and significant negative associations among %CD4 values and MD. These associations were bilateral and involved predominantly the long association fibers. Anatomically, these associations were more widespread when using KA as compared to FA. No statistically significant associations with HIV-RNA concentrations were found.

Conclusions: In HIV-positive subjects, associations between biochemical and diffusion-MRI variables are found along the association fibers, which connect brain areas involved in memory formation, providing a possible interpretation for the neurobiological substrate underlying cognitive disturbances in HIV.

Keywords: HIV; cART; diffusion tensor imaging; diffusional kurtosis imaging.