title: Direct MRI detection of impending plaque development in multiple sclerosis.
abstract: OBJECTIVE
  To detect and localize MRI signal changes prior to the parenchymal contrast enhancement that classically defines the radiologic onset of the developing white matter lesion in multiple sclerosis (MS).
  
  
  METHODS
  We reviewed 308 high-resolution (≤1 mm(3) voxels) MRI scans at 3T and 7T in 29 patients with active MS. The presence of pre-parenchymal enhancement abnormalities before the appearance of parenchymal enhancement was evaluated in all available scans.
  
  
  RESULTS
  Pre-enhancement signal changes were noted in 26 of 162 enhancing lesions (16%) as linear enhancement of the central vein and/or perivenular hyperintense signal on T2 fluid-attenuated inversion recovery or T2* images. They occur up to 2 months before focal enhancement within the parenchyma in 10% of cases.
  
  
  CONCLUSIONS
  In some lesions, the abrupt opening of the blood-brain barrier, detected by contrast enhancement on MRI, can have directly visible antecedent MRI changes centered on the central vein. We propose that these findings might be the basis for prior reports of subtle pre-parenchymal enhancement changes in quantitative MRI indices. In line with the venulocentric model of lesion development, our findings are consistent with the centrality of early perivenular events in lesion formation in vivo.
authors.affiliation: Division of Neuroimmunology and Neurovirology (M.A., G.N., P.S., I.C.M.C., D.S.R.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Neuroimaging Research Unit (M.A., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Absinta
authors.affiliation: Division of Neuroimmunology and Neurovirology (M.A., G.N., P.S., I.C.M.C., D.S.R.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Neuroimaging Research Unit (M.A., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Govind
authors.initials: G
authors.lastname: Nair
authors.affiliation: Division of Neuroimmunology and Neurovirology (M.A., G.N., P.S., I.C.M.C., D.S.R.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Neuroimaging Research Unit (M.A., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Pascal
authors.initials: P
authors.lastname: Sati
authors.affiliation: Division of Neuroimmunology and Neurovirology (M.A., G.N., P.S., I.C.M.C., D.S.R.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Neuroimaging Research Unit (M.A., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Irene C M
authors.initials: IC
authors.lastname: Cortese
authors.affiliation: Division of Neuroimmunology and Neurovirology (M.A., G.N., P.S., I.C.M.C., D.S.R.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Neuroimaging Research Unit (M.A., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
authors.affiliation: Division of Neuroimmunology and Neurovirology (M.A., G.N., P.S., I.C.M.C., D.S.R.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Neuroimaging Research Unit (M.A., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Reich