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. Highresolution, 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.

Combining Quantitative Susceptibility Mapping with Automatic Zero Reference (QSM0) and Myelin Water Fraction Imaging to Quantify Iron-Related Myelin Damage in Chronic Active MS Lesions

“…A subset of chronic lesions, identified as chronic active or slowly expanding lesions have been described as having a rim of iron-enriched pro-inflammatory (M1) activated microglia/macrophages (m/M). 1–4 M1 microglia release cytotoxins to adjacent oligodendrocytes, 5 limit remyelination and contribute to further demyelination in chronic active lesions. 3 Therefore, identifying MS lesions with iron accumulation may be able to predict tissue damage.…”

“…1, 3, 4, 7–9 Iron may be detected as hypointensity on T2 * weighted GRE magnitude image or its phase-enhanced version known as susceptibility weighted imaging (SWI). 8, 10 An R2 * (= 1/T2 * ) map computed from multi-echo GRE magnitude image can be used to estimate iron content.…”

MRI in the assessment and monitoring of multiple sclerosis: an update on best practice

“…112,130 The presence of iron is suggestive of microglia activity, and positive signal has been associated with chronic active MS lesions. 34,[131][132][133][134][135][136][137][138][139][140][141] Longitudinal QSM studies, conducted in our center, showed that lesion susceptibility increased as the lesion evolved from contrast enhanced to nonenhanced, indicating that it could be used as a biomarker. [142][143][144] All of these advanced magnetic resonance modalities require further validation in larger cohorts of patients and over a longitudinal time span.…”

Ultra-high-field (7.0 Tesla and above) MRI is now necessary to make the next step forward in understanding MS pathophysiology – YES

“…5 As stated earlier, another important gain associated with 7T MRI is the ability of exploiting different mechanisms of contrast. Over the last few years, the characterization of iron as a tracer of MS pathology 1,6,7 was made possible by the use of susceptibility-based 7T MRI. The latter opened to the study of microglia activation in patients with MS and the in vivo identification of the so-called slowly expanding lesions, 1,6,7 till then characterized only pathologically.…”

“…Over the last few years, the characterization of iron as a tracer of MS pathology 1,6,7 was made possible by the use of susceptibility-based 7T MRI. The latter opened to the study of microglia activation in patients with MS and the in vivo identification of the so-called slowly expanding lesions, 1,6,7 till then characterized only pathologically. 8 This new MRI approach will certainly change the way we measure Ultra-high-field (7.0 Tesla and above) MRI is now necessary to make the next step forward in understanding MS pathophysiology -YES F Bagnato and JC Gore MS disease progression and will extend the concept of disease activity beyond that of inflammation sustained by acute blood-brain barrier breakdown.…”