Evolution of the blood-brain barrier in newly forming multiple sclerosis lesions. Ann Neurol 2011 Jul;70(1):22-9
Date
06/29/2011Pubmed ID
21710622Pubmed Central ID
PMC3143223DOI
10.1002/ana.22472Scopus ID
2-s2.0-79960839634 (requires institutional sign-in at Scopus site) 139 CitationsAbstract
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.
INTERPRETATION: 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.
Author List
Gaitán MI, Shea CD, Evangelou IE, Stone RD, Fenton KM, Bielekova B, Massacesi L, Reich DSAuthor
Kaylan M. Fenton APP Outpatient in the Neurology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultBlood-Brain Barrier
Capillary Permeability
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Multiple Sclerosis, Relapsing-Remitting
Young Adult
