title: Diffusion tensor and volumetric magnetic resonance measures as biomarkers of brain damage in a small animal model of HIV.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  TBV and PV were smaller in Tg compared to control rats in young and middle-aged cohorts (p<0.0001). VV increased significantly (p = 0.005) over time in the longitudinal Tg cohort. There were lower FA (p<0.002) and higher MD (p<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 (p<0.03) while it did not change significantly in the control cohort over the same period of time (p>0.05).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Lentz
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Peterson
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Wael G
authors.initials: WG
authors.lastname: Ibrahim
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Dianne E
authors.initials: DE
authors.lastname: Lee
authors.affiliation: National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, Maryland, United States of America.
authors.forename: Joelle
authors.initials: J
authors.lastname: Sarlls
authors.affiliation: Magnetic Resonance Imaging Research Facility (NMRF), National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, Maryland, United States of America.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Lizak
authors.affiliation: Division of Intermural Research (DIR), National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, Maryland, United States of America.
authors.forename: Dragan
authors.initials: D
authors.lastname: Maric
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: William C
authors.initials: WC
authors.lastname: Reid
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Dima A
authors.initials: DA
authors.lastname: Hammoud
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D015658:HIV Infections / Q000378:metabolism / Q000473:pathology*; D015497:HIV-1; D006801:Humans; D059906:Neuroimaging; D051381:Rats; D011916:Rats, Inbred F344; D055647:Rats, Transgenic
chemical_list: D015415:Biomarkers