Conventional and quantitative MRI in a novel feline model of demyelination and endogenous remyelination

Abstract

Background: The feeding of irradiated food to healthy adult cats results in widespread, noninflammatory demyelination of the central nervous system (CNS); a return to a normal diet results in endogenous remyelination with functional recovery. This recently discovered, reversible disease might provide a compelling clinical neuroimaging model system for the development and testing of myelin-directed MRI methods as well as future remyelination therapies.

Purpose: Identify the noninvasive imaging characteristics of this new disease model and determine whether it features measurable changes on conventional and quantitative MRI.

Study type: Pilot study.

Animal model: Ten adult cats at various stages of demyelinating disease induced by an irradiated diet (35-55 kGy), and during recovery following a return to a normal diet.

Field strength/sequence: Conventional (T₂ -weighted) and quantitative (diffusion tensor, magnetization transfer) at 3T.

Assessment: MRI of the brain, optic nerves, and cervical spinal cord; a subset of diseased cats was euthanized for comparative histopathology.

Statistical tests: Descriptive statistics.

Results: Disease produced T₂ prolongation, progressing from patchy to diffuse throughout most of the cerebral white matter (eventually involving U-fibers) and spinal cord (primarily dorsal columns, reminiscent of subacute combined degeneration but without evidence of B12 deficiency). Magnetization transfer parameters decreased by 50-53% in cerebral white matter and by 25-30% in optic nerves and spinal cord dorsal columns. Fractional diffusion anisotropy decreased by up to 20% in pyramidal tracts, primarily driven by increased radial diffusivity consistent with axon preservation. Histopathology showed scattered myelin vacuolation of major white matter tracts as well as many thin myelin sheaths consistent with remyelination in the recovery phase, which was detectable on magnetization transfer imaging.

Data conclusion: Feline irradiated diet-induced demyelination features noninvasively imageable and quantifiable demyelination and remyelination of the CNS. It is therefore a compelling clinical neuroimaging model system.

Level of evidence: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1304-1311.

Keywords: animal models; demyelination; myelin repair; quantitative MRI; white matter imaging.