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Published on: April 14, 2014
Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions
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.
Insights
A persistent phase rim in multiple sclerosis (MS) lesions indicates failed repair and ongoing tissue damage. This finding aids in evaluating therapies for chronic active MS lesions.
Area of Science:
- Neuroimaging
- Neuropathology
- Multiple Sclerosis Research
Background:
- Active multiple sclerosis (MS) lesions can be contained by immune reactions at their edges.
- This containment may involve blood-brain barrier opening, visualized on MRI as contrast enhancement and a phase rim.
- Characterizing these features could track tissue changes and assess therapies for chronic active lesions.
Purpose of the Study:
- To investigate the evolution of phase rims in MS lesions using high-resolution 7-tesla MRI.
- To correlate MRI findings with histopathology in progressive MS.
- To determine if phase rims can predict lesion behavior and tissue damage over time.
Main Methods:
- 17 MS patients underwent serial 7-tesla MRI scans (T1-weighted, susceptibility-weighted, dynamic contrast-enhanced).
- Lesion evolution, phase rim presence, volume, and T1 hypointensity were tracked over 12 months.
- Histopathology of phase rims was examined in 3 progressive MS autopsy cases.
Main Results:
- Phase rims colocalized with initial contrast enhancement in centripetal lesions.
- Persistent phase rims were observed in 12/22 lesions after enhancement resolved.
- Persistent rims correlated with less lesion shrinkage and increased T1 hypointensity, indicative of chronic inflammation and tissue damage.
Conclusions:
- A persistent phase rim in early MS lesion evolution suggests impaired repair and irreversible tissue damage.
- These 'smoldering' lesions may exert detrimental effects in later stages of MS.
- Phase rim characterization offers a potential biomarker for monitoring MS progression and therapeutic response.
