Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions
Martina Absinta, … , Irene C.M. Cortese, Daniel S. Reich
Martina Absinta, … , Irene C.M. Cortese, Daniel S. Reich
Published June 6, 2016
Citation Information: J Clin Invest. 2016;126(7):2597-2609. https://doi.org/10.1172/JCI86198.
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Clinical Research and Public Health Neuroscience

Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions

Abstract

BACKGROUND. In some active multiple sclerosis (MS) lesions, a strong immune reaction at the lesion edge may contain growth and thereby isolate the lesion from the surrounding parenchyma. Our previous studies suggest that this process involves opening of the blood-brain barrier in capillaries at the lesion edge, seen on MRI as centripetal contrast enhancement and a colocalized phase rim. We hypothesized that using these features to characterize early lesion evolution will allow in vivo tracking of tissue degeneration and/or repair, thus improving the evaluation of potential therapies for chronic active lesions.

METHODS. Centripetally and centrifugally enhancing lesions were studied in 17 patients with MS using 7-tesla MRI. High-resolution, susceptibility-weighted, T1-weighted (before/after gadolinium), and dynamic contrast–enhanced scans were acquired at baseline and months 1, 3, 6, and 12. For each lesion, time evolution of the phase rim, lesion volume, and T1 hypointensity were assessed. In autopsies of 3 progressive MS cases, the histopathology of the phase rim was determined.

RESULTS. In centripetal lesions, a phase rim colocalized with initial contrast enhancement. In 12 of 22, this phase rim persisted after enhancement resolved. Compared with centripetal lesions with transient rim, those with persistent rim had less volume shrinkage and became more T1 hypointense between months 3 and 12. No centrifugal lesions developed phase rims at any time point. Pathologically, persistent rims corresponded to an iron-laden inflammatory myeloid cell population at the edge of chronic demyelinated lesions.

CONCLUSION. In early lesion evolution, a persistent phase rim in lesions that shrink least and become more T1 hypointense over time suggests that the rim might mark failure of early lesion repair and/or irreversible tissue damage. In later stages of MS, phase rim lesions continue to smolder, exerting detrimental effects on affected brain tissue.

TRIAL REGISTRATION. NCT00001248.

FUNDING. The Intramural Research Program of NINDS supported this study.

Authors

Martina Absinta, Pascal Sati, Matthew Schindler, Emily C. Leibovitch, Joan Ohayon, Tianxia Wu, Alessandro Meani, Massimo Filippi, Steven Jacobson, Irene C.M. Cortese, Daniel S. Reich

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Figure 4

Longitudinal lesion volume and T1-hypointensity assessment.

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Longitudinal lesion volume and T1-hypointensity assessment. (A) Semiloga...
(A) Semilogarithmic plot of the longitudinal volume for each lesion according to participant age and lesion group (G1, G2, G3). Three main observations about centripetal lesions with persistent phase rim derive from this graph: (a) their lesion volume shrinkage over time tends to plateau after the first 3 months; (b) their mean lesion volume is higher at all time points; and (c) compared with centripetal lesions with transient phase rims, they tend to occur in older individuals. (B) Percentage of lesion volume shrinkage (mean ± SD) between M3 and M12 for each lesion group. (C) Lesional T1 hypointensity at M12 for each lesion group (mean ± SD; T1 signal intensity is expressed in units of SD of normal-appearing white matter signal). In G1, red dots show the in vivo mean T1 hypointensity of the 5 pathologically assessed demyelinated lesions with phase rim. G1: centripetal lesions with persistent phase rim; G2: centripetal lesions with transient phase rim; G3: centrifugal lesions.