Early detection of neuropathophysiology using diffusion-weighted magnetic resonance imaging in asymptomatic cats with feline immunodeficiency viral infection

Abstract

HIV infection results in a highly prevalent syndrome of cognitive and motor disorders designated as HIV-associated dementia (HAD). Neurologic dysfunction resembling HAD has been documented in cats infected with strain PPR of the feline immunodeficiency virus (FIV), whereas another highly pathogenic strain (C36) has not been known to cause neurologic signs. Animals experimentally infected with equivalent doses of FIV-C36 or FIV-PPR, and uninfected controls were evaluated by magnetic resonance diffusion-weighted imaging (DW-MRI) and spectroscopy (MRS) at 17.5 – 18 weeks post-infection, as part of a study of viral clade pathogenesis in FIV infected cats. Goals of the MR imaging portion of the project were to determine whether this methodology was capable of detecting early neuropathophysiology in the absence of outward manifestation of neurological signs, and to compare MR imaging results for the two viral strains expected to have differing degrees of neurologic effects. We hypothesized that there would be increased diffusion, evidenced by the apparent diffusion coefficient as measured by DW-MRI, and altered metabolite ratios measured by MRS, in the brains of FIV-PPR infected cats relative to C36-infected cats and uninfected controls. Increased apparent diffusion coefficients were seen in the white matter, gray matter, and basal ganglia of both the PPR and C36 infected (asymptomatic) cats. Thalamic MRS metabolite ratios did not differ between groups. The equivalently increased diffusion by DW-MRI suggests similar indirect neurotoxicity mechanisms for the two viral genotypes. DW-MRI is a sensitive tool to detect neuropathophysiological changes in vivo that could be useful during longitudinal studies of FIV.

Strain-specific viral distribution and neuropathology of feline immunodeficiency virus

“…Neuroimaging results from MRI did not produce any significant differences in regard to brain diffusion. This is contrary to findings from a previous study that revealed increased brain diffusion in both PPR and C36-infected cats (Bucy et al, 2010). …”

“…Images were obtained with cats under general anesthesia maintained with isoflurane gas via a non-rebreathing circuit and positive pressure ventilation. MRI and DW-MRI were performed as previously described (Bucy et al, 2010). …”

Novel Gammaherpesviruses in North American Domestic Cats, Bobcats, and Pumas: Identification, Prevalence, and Risk Factors

“…Archived blood cell DNA from specific-pathogen-free domestic cats was obtained from three previous studies (22)(23)(24). BoHV4 and feline herpesvirus 1 (FeHV1) DNAs were extracted from infected cell culture supernatants (provided by Hana Van Campen and Sandra Quackenbush, respectively, both of Colorado State University) using a QIAamp DNA blood kit (Qiagen).…”

Susceptibility of Domestic Cats to Chronic Wasting Disease

“…Anatomic brain magnetic resonance imaging (MRI) scans, including proton density, T2-weighted, fluid attenuated inversion recovery (FLAIR), and T1-weighted (pre-and postcontrast) scans were performed on 10 i.c.-inoculated cats: 6 clinically ill (1 primary passage, 5 secondary passage), 2 asymptomatic (primary passage), and 2 age-matched sham controls, as well as 1 uninoculated age-matched control. MRI was done with a Signa LX 1.5 T MR HiSpeed Plus system (General Electric), as previously described (29). Briefly, anesthetized cats were positioned sternally with the head centered within the quadrature head coil.…”