Diffusion tensor and volumetric magnetic resonance measures as biomarkers of brain damage in a small animal model of HIV.
Lentz, MR; Peterson, KL; Ibrahim, WG; Lee, DE; Sarlls, J; Lizak, MJ; Maric, D; Reid, WC; Hammoud, DA
PloS one
9
e105752
2014
Show Abstract
There are currently no widely accepted neuro-HIV small animal models. We wanted to validate the HIV-1 Transgenic rat (Tg) as an appropriate neuro-HIV model and then establish in vivo imaging biomarkers of neuropathology, within this model, using MR structural and diffusion tensor imaging (DTI).Young and middle-aged Tg and control rats were imaged using MRI. A subset of middle-aged animals underwent longitudinal repeat imaging six months later. Total brain volume (TBV), ventricular volume (VV) and parenchymal volume (PV = TBV-VV) were measured. Fractional anisotropy (FA) and mean diffusivity (MD) values of the corpus callosum (CC) were calculated from DTI data.TBV and PV were smaller in Tg compared to control rats in young and middle-aged cohorts (pless than 0.0001). VV increased significantly (p = 0.005) over time in the longitudinal Tg cohort. There were lower FA (pless than 0.002) and higher MD (pless than 0.003) values in the CC of middle-aged Tg rats compared to age-matched controls. Longitudinally, MD significantly decreased over time in Tg rats (pless than 0.03) while it did not change significantly in the control cohort over the same period of time (pgreater than 0.05).We detected brain volume loss in the Tg rat, probably due to astrocytic dysfunction/loss, loss of structural/axonal matrix and striatal neuronal loss as suggested by immunofluorescence. Increased MD and decreased FA in the CC probably reflect microstructural differences between the Tg and Control rats which could include increased extracellular space between white matter tracts, demyelination and axonal degeneration, among other pathologies. We believe that the Tg rat is an adequate model of neuropathology in HIV and that volumetric MR and DTI measures can be potentially used as biomarkers of disease progression. | 25144656
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