central vein sign and iron in lesion as biomarkers

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frodo
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central vein sign and iron in lesion as biomarkers

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The prevalence of paramagnetic rim lesions in multiple sclerosis: A systematic review and meta-analysis

https://journals.plos.org/plosone/artic ... ne.0256845

Introduction

Susceptibility-based magnetic resonance imaging (MRI), which distinguishes tissues based on their magnetic susceptibility, is exquisitely sensitive to mineral content in the brain and has been applied to a variety of neurological conditions [1]. While phase images have historically been largely disregarded, they have recently gained renewed interest given their potential to inform about local susceptibility effects. Highlighting their significance, susceptibility-weighted imaging (SWI), a technique combining magnitude and phase information, offers excellent contrast between tissues of different magnetic susceptibilities, allowing the qualitative assessment of diamagnetic and paramagnetic features in the brain with high sensitivity [2]. Susceptibility-based imaging approaches also include quantitative susceptibility mapping (QSM), which allows absolute iron concentrations in tissues to be estimated [3].

Insights gained from combined pathological and radiological studies have resulted in an increasing interest in the potential application of susceptibility-based MRI in multiple sclerosis (MS) [4–6]. Classification systems for white matter lesions in MS have predominantly been derived from histological characterisation, broadly dividing them into ‘active’, ‘inactive’ and ‘remyelinated’ lesions based on their inflammatory cell distribution and demyelination profile [4, 7, 8]. However, brain tissue constituents such as myelin, iron and calcium have been found to generate susceptibility effects, raising the possibility that pathological changes in MS may be captured in vivo through SWI biomarkers [9, 10]. Detectable paramagnetic effects due to iron accumulation are associated with a range of neurodegenerative diseases including MS, and have generated particular attention in this regard [10, 11].

Pathological analysis of MS lesions that are surrounded by a rim of hypointense signal on susceptibility-based MRI has demonstrated corresponding iron deposition, with foci of activated myeloid cells around the lesion margins [9, 12, 13]. The presence of iron-enriched macrophages/microglia could potentially follow the uptake of iron released in response to insult to myelin and oligodendrocytes, although this remains to be established. These ‘rim’ lesions, which have been variously termed in the literature, have subsequently been suggested to reflect chronic inflammatory demyelination in MS patients [9, 12, 13].

Moreover, recent studies have shown that ‘chronic active lesions’, which are histologically characterised by ongoing demyelination at the edge of an inactive demyelinated core and are believed to predominate in progressive forms of MS [4, 14, 15], may be identified on MRI as non-gadolinium-enhancing rim lesions [13, 16]. MS patients with such ‘chronic active lesions’ have been found to experience earlier progression in disability and decreased brain volumes, indicating their potential prognostic significance [13]. Longitudinal imaging studies have also shown that rim lesions are more likely to expand over time compared with those without rims [12, 13], and slow expansion has been suggested as an alternative marker for chronic active demyelination, although this has been explored in only a few in vivo studies to date [17].

In addition to paramagnetic rims, susceptibility-based MRI has also revealed central veins within white matter lesions; both features appear to be highly specific to MS, and have therefore been proposed as possible diagnostic markers [18–20].

While the prevalence of the central vein sign has previously been systematically reviewed [21], an estimate of the pooled prevalence of paramagnetic rim lesions in MS patients has, to our knowledge, not been calculated to date. Here, we perform a systematic review and meta-analysis of the literature on rim lesions, in order to assess their prevalence both on a per-lesion basis and at a patient-level. Given the lack of consensus within the published literature, we conduct separate meta-analyses for rim lesions and chronic active lesions, which are defined as non-gadolinium enhancing rim lesions.
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