Disease correlates of rim lesions on quantitative susceptibility mapping in multiple sclerosis

Abstract

Quantitative susceptibility mapping (QSM), an imaging technique sensitive to brain iron, has been used to detect paramagnetic rims of iron-laden active microglia and macrophages in a subset of multiple sclerosis (MS) lesions, known as rim+ lesions, that are consistent with chronic active lesions. Because of the potential impact of rim+ lesions on disease progression and tissue damage, investigating their influence on disability and neurodegeneration is critical to establish the impact of these lesions on the disease course. This study aimed to explore the relationship between chronic active rim+ lesions, identified as having a hyperintense rim on QSM, and both clinical disability and imaging measures of neurodegeneration in patients with MS. The patient cohort was composed of 159 relapsing–remitting multiple sclerosis patients. The Expanded Disability Status Scale (EDSS) and Brief International Cognitive Assessment for Multiple Sclerosis, which includes both the Symbol Digit Modalities Test and California Verbal Learning Test-II, were used to assess clinical disability. Cortical thickness and thalamic volume were evaluated as imaging measures of neurodegeneration. A total of 4469 MS lesions were identified, of which 171 QSM rim+ (3.8%) lesions were identified among 57 patients (35.8%). In a multivariate regression model, as the overall total lesion burden increased, patients with at least one rim+ lesion on QSM performed worse on both physical disability and cognitive assessments, specifically the Symbol Digit Modalities Test (p = 0.010), California Verbal Learning Test-II (p = 0.030), and EDSS (p = 0.001). In a separate univariate regression model, controlling for age (p < 0.001) and having at least one rim+ lesion was related to more cortical thinning (p = 0.03) in younger patients (< 45 years). Lower thalamic volume was associated with older patients (p = 0.038) and larger total lesion burden (p < 0.001); however, the association did not remain significant with rim+ lesions (p = 0.10). Our findings demonstrate a novel observation that chronic active lesions, as identified on QSM, modify the impact of lesion burden on clinical disability in MS patients. These results support further exploration of rim+ lesions for therapeutic targeting in MS to reduce disability and subsequent neurodegeneration.

Longitudinal clinical study of patients with iron rim lesions in multiple sclerosis

“…We found that the presence of IRLs was associated with worsened clinical disability in a cohort of 91 patients, particularly if patients had more than four IRLs at their MRI scan, supporting the notion of unfavourable prognosis associated with IRLs presence. [13][14][15] In line with others, at least one IRL was detected in almost half of our patients, 7,28 and IRLs were more prevalent in SPMS patients compared to CIS and all other MS subtypes. 7,10,15,[29][30][31][32] We found patients with IRLs had a more aggressive disease (greater WML number and volume, higher disability scores at baseline and follow-up), corroborating findings from earlier studies.…”

“…We found that the presence of IRLs was associated with worsened clinical disability in a cohort of 91 patients, particularly if patients had more than four IRLs at their MRI scan, supporting the notion of unfavourable prognosis associated with IRLs presence. 13 – 15 …”

“…10,11 MRI 7 and neuropathological 10,12 studies have reported that IRLs are present in more than half of MS patients and have been associated with clinical disability. It has been speculated that IRLs could serve as an imaging biomarker to predict future physical disability in MS. 13,14 Two recent studies reported that patients with IRLs had more aggressive disease course but their conclusions are tempered by either their sample size or follow-up duration. 13,15 In this large retrospective study, we aim to evaluate the association of IRLs on 7 T SWI-filtered phase images 9 with clinical outcomes after a long clinical follow-up.…”

QSMRim-Net: Imbalance-Aware Learning for Identification of Chronic Active Multiple Sclerosis Lesions on Quantitative Susceptibility Maps

“…We also obtained results for all rim+ lesion identification algorithms on a patient-level, showing that QSMRim-NET outperformed the other methods. In a previous study, as the overall total lesion burden increased, patients with at least one rim+ lesion on QSM performed worse on both physical disability and cognitive assessments [17]. Having four or more chronic active lesions on phase imaging has also been shown to correlate with disability [16].…”

“…Chronic active lesions are visible with in-vivo susceptibility magnetic resonance imaging (MRI) techniques, where these lesions show a paramagnetic rim [2,4,[6][7][8][9][10][11][12][13][14][15] on the edge. The presence of chronic active multiple sclerosis lesions is associated with a more severe disease course [14,[16][17][18][19] and there is currently much interest in using these lesions as an imaging biomarker.…”