title: Evolution of the blood-brain barrier in newly forming multiple sclerosis lesions.
abstract: OBJECTIVE
  Multiple sclerosis (MS) lesions develop around small, inflamed veins. New lesions enhance with gadolinium on magnetic resonance imaging (MRI), reflecting disruption of the blood-brain barrier (BBB). Single time point results from pathology and standard MRI cannot capture the spatiotemporal expansion of lesions. We investigated the development and expansion of new MS lesions, focusing on the dynamics of BBB permeability.
  
  
  METHODS
  We performed dynamic contrast-enhanced (DCE) MRI in relapsing-remitting MS. We obtained data over 65 minutes, during and after gadolinium injection. We labeled spatiotemporal enhancement dynamics as centrifugal when initially central enhancement expanded outward and centripetal when initially peripheral enhancement gradually filled the center.
  
  
  RESULTS
  We detected 34 enhancing lesions in 200 DCE-MRI scans. In 65%, enhancement first appeared as a closed ring; in 18%, as a nodule; and in 18%, as an open ring. Lesions with initially nodular enhancement were smaller than those initially enhancing as rings (p < 0.0001). All initially nodular lesions enhanced centrifugally, whereas initially ringlike lesions enhanced centripetally, becoming nodular if small (82%) or nearly nodular if larger (18%). Open-ring lesions were periventricular or juxtacortical and enhanced centripetally. Centrifugally enhancing lesions evolved into centripetally enhancing lesions over several days.
  
  
  CONCLUSIONS
  The rapid change of enhancement dynamics from centrifugal to centripetal reflects the outward growth of MS lesions around their central vein and suggests that factors mediating lesion growth and tissue repair derive from different locations at different times. We propose a model of new lesion growth that unites our imaging observations with existing pathology data.
authors.affiliation: Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: María I
authors.initials: MI
authors.lastname: Gaitán
authors.forename: Colin D
authors.initials: CD
authors.lastname: Shea
authors.forename: Iordanis E
authors.initials: IE
authors.lastname: Evangelou
authors.forename: Roger D
authors.initials: RD
authors.lastname: Stone
authors.forename: Kaylan M
authors.initials: KM
authors.lastname: Fenton
authors.forename: Bibiana
authors.initials: B
authors.lastname: Bielekova
authors.forename: Luca
authors.initials: L
authors.lastname: Massacesi
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Reich
mesh_terms: D000328:Adult; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology*; D002199:Capillary Permeability / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000639:trends; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult