Evolution of the blood–brain barrier in newly forming multiple sclerosis lesions
Version of Record online: 27 JUN 2011
Copyright © 2011 American Neurological Association
Annals of Neurology
Volume 70, Issue 1, pages 22–29, July 2011
How to Cite
Gaitán, M. I., Shea, C. D., Evangelou, I. E., Stone, R. D., Fenton, K. M., Bielekova, B., Massacesi, L. and Reich, D. S. (2011), Evolution of the blood–brain barrier in newly forming multiple sclerosis lesions. Ann Neurol., 70: 22–29. doi: 10.1002/ana.22472
- Issue online: 22 JUL 2011
- Version of Record online: 27 JUN 2011
- Accepted manuscript online: 11 MAY 2011 08:15AM EST
- Manuscript Accepted: 3 MAY 2011
- Manuscript Revised: 8 APR 2011
- Manuscript Received: 29 DEC 2010
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.
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.
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.
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. ANN NEUROL 2011;