title: MRI reveals that early changes in cerebral blood volume precede blood-brain barrier breakdown and overt pathology in MS-like lesions in rat brain.
abstract: Magnetic resonance imaging (MRI) is an established clinical tool for diagnosing multiple sclerosis (MS), the archetypal central nervous system neuroinflammatory disease. In this study, we have used a model of delayed-type hypersensitivity in the rat brain, which bears many of the hallmarks of an MS lesion, to investigate the development of MRI-detectable changes before the appearance of conventional indices of lesion development. In addition, we have correlated the MRI-detectable changes with the developing histopathology. Significant increases in regional cerebral blood volume (rCBV) preceded overt changes in blood-brain barrier (BBB) permeability, T2 relaxation and the diffusion properties of tissue water. Thus, changes in rCBV might be a more sensitive indicator of lesion onset than the conventional indices used clinically in MS patients, such as contrast enhancement. In addition, we show that BBB breakdown, and consequent edema formation, are more closely correlated with astrogliosis than any other histopathologic changes, while regions of T1 and T2 hypointensity appear to reflect hypercellularity.
authors.affiliation: Experimental Neuroimaging Group, Department of Biochemistry, University of Oxford, Oxford, UK. kerry.broom@bioch.ox.ac.uk
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Broom
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Anthony
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Blamire
authors.forename: Sara
authors.initials: S
authors.lastname: Waters
authors.forename: Peter
authors.initials: P
authors.lastname: Styles
authors.forename: Victor Hugh
authors.initials: VH
authors.lastname: Perry
authors.forename: Nicola R
authors.initials: NR
authors.lastname: Sibson
mesh_terms: D000818:Animals; D001810:Blood Volume / Q000502:physiology*; D001812:Blood-Brain Barrier / Q000473:pathology*; D001921:Brain / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000473:pathology; D004195:Disease Models, Animal; D006968:Hypersensitivity, Delayed / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000503:physiopathology; D010539:Permeability; D011856:Radiographic Image Enhancement; D051381:Rats; D011917:Rats, Inbred Lew