Quantitative susceptibility mapping in multiple sclerosis.
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ABSTRACT:
SUBMITTER: Langkammer C
PROVIDER: S-EPMC3632806 | biostudies-other | 2013 May
REPOSITORIES: biostudies-other
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Project description:PurposeTo assess multiple sclerosis (MS) lesions at various ages by using quantitative susceptibility mapping (QSM) and conventional magnetic resonance (MR) imaging.Materials and methodsRetrospectively selected were 32 clinically confirmed MS patients (nine men and 23 women; 39.3 years ± 10.9) who underwent two MR examinations (interval, 0.43 years ± 0.16) with three-dimensional gradient-echo sequence from August 2011 to August 2012. To estimate the ages of MS lesions, MR examinations performed 0.3-10.6 years before study examinations were studied. Hyperintensity on T2-weighted images was used to define MS lesions. QSM images were reconstructed from gradient-echo data. Susceptibility of MS lesions and temporal rates of change were obtained from QSM images. Lesion susceptibilities were analyzed by t test with intracluster correlation adjustment and Bonferroni correction in multiple comparisons.ResultsMR imaging of 32 patients depicted 598 MS lesions, of which 162 lesions (27.1%) in 23 patients were age measurable and six (1.0%) were only visible at QSM. The susceptibilities relative to normal-appearing white matter (NAWM) were 0.53 ppb ± 3.34 for acute enhanced lesions, 38.43 ppb ± 13.0 (positive; P < .01) for early to intermediately aged nonenhanced lesions, and 4.67 ppb ± 3.18 for chronic nonenhanced lesions. Temporal rates of susceptibility changes relative to cerebrospinal fluid were 12.49 ppb/month ± 3.15 for acute enhanced lesions, 1.27 ppb/month ± 2.31 for early to intermediately aged nonenhanced lesions, and -0.004 ppb/month ± 0 for chronic nonenhanced lesions.ConclusionMagnetic susceptibility of MS lesions increased rapidly as it changed from enhanced to nonenhanced, it attained a high susceptibility value relative to NAWM during its initial few years (approximately 4 years), and it gradually dissipated back to susceptibility similar to that of NAWM as it aged, which may provide new insight into pathophysiologic features of MS lesions. Online supplemental material is available for this article.
| S-EPMC4263629 | biostudies-literature
Project description:BackgroundQuantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising non-invasive tool for multiple sclerosis (MS) in research and clinical practice.ObjectiveWe performed a systematic review and meta-analysis on the use of QSM in MS.MethodsOur review was prospectively registered on PROSPERO (CRD42022309563). We searched five databases for studies published between inception and 30th April 2023. We identified 83 English peer-reviewed studies that applied QSM images on MS cohorts. Fifty-five included studies had at least one of the following outcome measures: deep grey matter QSM values in MS, either compared to healthy controls (HC) (k = 13) or correlated with the score on the Expanded Disability Status Scale (EDSS) (k = 7), QSM lesion characteristics (k = 22) and their clinical correlates (k = 17), longitudinal correlates (k = 11), histological correlates (k = 7), or correlates with other imaging techniques (k = 12). Two meta-analyses on deep grey matter (DGM) susceptibility data were performed, while the remaining findings could only be analyzed descriptively.ResultsAfter outlier removal, meta-analyses demonstrated a significant increase in the basal ganglia susceptibility (QSM values) in MS compared to HC, caudate (k = 9, standardized mean difference (SDM) = 0.54, 95 % CI = 0.39-0.70, I2 = 46 %), putamen (k = 9, SDM = 0.38, 95 % CI = 0.19-0.57, I2 = 59 %), and globus pallidus (k = 9, SDM = 0.48, 95 % CI = 0.28-0.67, I2 = 60 %), whereas thalamic QSM values exhibited a significant reduction (k = 12, SDM = -0.39, 95 % CI = -0.66--0.12, I2 = 84 %); these susceptibility differences in MS were independent of age. Further, putamen QSM values positively correlated with EDSS (k = 4, r = 0.36, 95 % CI = 0.16-0.53, I2 = 0 %). Regarding rim lesions, four out of seven studies, representing 73 % of all patients, reported rim lesions to be associated with more severe disability. Moreover, lesion development from initial detection to the inactive stage is paralleled by increasing, plateauing (after about two years), and gradually decreasing QSM values, respectively. Only one longitudinal study provided clinical outcome measures and found no association. Histological data suggest iron content to be the primary source of QSM values in DGM and at the edges of rim lesions; further, when also considering data from myelin water imaging, the decrease of myelin is likely to drive the increase of QSM values within WM lesions.ConclusionsWe could provide meta-analytic evidence for DGM susceptibility changes in MS compared to HC; basal ganglia susceptibility is increased and, in the putamen, associated with disability, while thalamic susceptibility is decreased. Beyond these findings, further investigations are necessary to establish the role of QSM in MS for research or even clinical routine.
| S-EPMC11002889 | biostudies-literature
Project description: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.
| S-EPMC8924224 | biostudies-literature
Project description:Chronic active multiple sclerosis lesions, characterized by a hyperintense rim of iron-enriched, activated microglia and macrophages, have been linked to greater tissue damage. Post-mortem studies have determined that chronic active lesions are primarily related to the later stages of multiple sclerosis; however, the occurrence of these lesions, and their relationship to earlier disease stages may be greatly underestimated. Detection of chronic active lesions across the patient spectrum of multiple sclerosis requires a validated imaging tool to accurately identify lesions with persistent inflammation. Quantitative susceptibility mapping provides efficient in vivo quantification of susceptibility changes related to iron deposition and the potential to identify lesions harbouring iron-laden inflammatory cells. The PET tracer 11C-PK11195 targets the translocator protein expressed by activated microglia and infiltrating macrophages. Accordingly, this study aimed to validate that lesions with a hyperintense rim on quantitative susceptibility mapping from both relapsing and progressive patients demonstrate a higher level of innate immune activation as measured on 11C-PK11195 PET. Thirty patients were enrolled in this study, 24 patients had relapsing remitting multiple sclerosis, six had progressive multiple sclerosis, and all patients had concomitant MRI with a gradient echo sequence and PET with 11C-PK11195. A total of 406 chronic lesions were detected, and 43 chronic lesions with a hyperintense rim on quantitative susceptibility mapping were identified as rim+ lesions. Susceptibility (relative to CSF) was higher in rim+ (2.42 ± 17.45 ppb) compared to rim- lesions (-14.6 ± 19.3 ppb, P < 0.0001). Among rim+ lesions, susceptibility within the rim (20.04 ± 14.28 ppb) was significantly higher compared to the core (-5.49 ± 14.44 ppb, P < 0.0001), consistent with the presence of iron. In a mixed-effects model, 11C-PK11195 uptake, representing activated microglia/macrophages, was higher in rim+ lesions compared to rim- lesions (P = 0.015). Validating our in vivo imaging results, multiple sclerosis brain slabs were imaged with quantitative susceptibility mapping and processed for immunohistochemistry. These results showed a positive translocator protein signal throughout the expansive hyperintense border of rim+ lesions, which co-localized with iron containing CD68+ microglia and macrophages. In conclusion, this study provides evidence that suggests that a hyperintense rim on quantitative susceptibility measure within a chronic lesion is a correlate for persistent inflammatory activity and that these lesions can be identified in the relapsing patients. Utilizing quantitative susceptibility measure to differentiate chronic multiple sclerosis lesion subtypes, especially chronic active lesions, would provide a method to assess the impact of these lesions on disease progression.
| S-EPMC6308309 | biostudies-literature
Project description:BackgroundSusceptibility MRI techniques, such as phase and quantitative susceptibility mapping (QSM) reveal lesion heterogeneity in MS, including the presence of lesions with outer rims suggestive of iron accumulation in macrophages and microglia, indicative of chronic-active inflammatory white matter lesions (WMLs).ObjectiveTo evaluate the in vivo relationship between chronic-active WMLs (as visualized by rimmed lesions on QSM) and several clinical metrics.Methods39 patients (15 men, 24 women) with MS underwent 7 Tesla brain MRIs and clinical evaluation. Contrast patterns of lesions identified on FLAIR and quantitative susceptibility maps were reviewed and compared to demographic characteristics and disability scores.Results1279 lesions were identified on FLAIR MRI; 846 (66.2%) of these were visible on QSM, 119 (14.1%) of which had visible rims. Lesions visible on QSM were more likely to have rims in men (16.1%, vs 4.9% in women, p=0.009). In a logistic regression model accounting for several factors, male sex conferred a >10-fold risk of having ≥1 rimmed lesion(s) (p=0.026).ConclusionOur findings provide in vivo support for the body of histopathologic literature indicating sex-specific differences in MS WML formation and suggest that QSM can be used to study these sex differences in the future.
| S-EPMC7606497 | biostudies-literature
Project description:Within multiple sclerosis (MS) lesions iron is present in chronically activated microglia. Thus, iron detection with MRI might provide a biomarker for chronic inflammation within lesions. Here, we examine contributions of iron and myelin to magnetic susceptibility of lesions on quantitative susceptibility mapping (QSM).Fixed MS brain tissue was assessed with MRI including gradient echo data, which was processed to generate field (phase), R2* and QSM. Five lesions were sectioned and evaluated by immunohistochemistry for presence of myelin, iron and microglia/macrophages. Two of the lesions had an elemental analysis for iron concentration mapping, and their phospholipid content was estimated from the difference in the iron and QSM data.Three of the five lesions had substantial iron deposition that was associated with microglia and positive susceptibility values. For the two lesions with elemental analysis, the QSM derived phospholipid content maps were consistent with myelin labeled histology.Positive susceptibility values with respect to water indicate the presence of iron in MS lesions, although both demyelination and iron deposition contribute to QSM.
| S-EPMC4333139 | biostudies-literature
Project description:Background: Multiple sclerosis (MS) patients have a wide spectrum of severity and responses to therapy; the personalization of treatment relies on sensitive and specific biomarkers. Previous studies have suggested that susceptibility contrast in demyelinated plaques is associated with iron-related pathology in multiple sclerosis which may indicate clinical severity. The aims of this study were to characterize the spatial distribution of MS lesions with different iron patterns by using quantitative susceptibility mapping and to explore neuroradiological findings that correlate with poor clinical outcome. Methods: Twenty-six patients with relapsing-remitting MS [14 men, 12 women; mean age, 29 ± 8 (standard deviation) years; age range, 21-52 years] were included in this study. Differences in lesion number, T2 volume, and susceptibility were compared among lesions subcategorized by location and by the presence or absence of a hyperintense rim on quantitative susceptibility mapping. Associations between these imaging features and clinical outcomes including Expanded Disability Status Scale scores and annual relapse rates were investigated. Results: A total of 811 unifocal MS lesions were included, and their QSM patterns were nodular hyperintensity with no rim (rim-, 540, 67%) or with a hyperintense rim on the edge (rim+, 172, 21%) and nodular isointensity (99, 12%). Rim+ lesions had significantly larger volume (115 ± 142 vs. 166 ± 185 mm3, p < 0.001) and lower susceptibility (4 ± 15 vs. 8 ± 16 ppb, p < 0.05) than rim- lesions. More rim+ lesions were found in periventricular areas [median, 45%; interquartile range (IQR), 36%], whereas a larger proportion of rim- lesions were distributed in juxtacortical (median, 32%; IQR, 21%) and deep white matter (median, 38%; IQR, 22%) areas. The annual relapse rate was positively correlated with the proportion of periventricular rim+ lesions (p < 0.001, r = 0.65) and the proportion of subtentorial rim+ lesions (p < 0.05, r = 0.40). Additionally, a significant association was found between the burden of periventricular rim+ lesions (β = 0.64, p < 0.001) and the burden of subtentorial rim- lesions (β = 0.36, p < 0.05). Conclusions: A high number or lesion burden of periventricular rim+ lesions or subtentorial lesions is associated with frequent clinical relapses.
| S-EPMC8299522 | biostudies-literature
Project description:Background and purposeT2 hypointensity in the basal ganglia of patients with MS has been associated with clinical progression and cognitive decline. Our objectives were the following: 1) to compare signal in T2WI, R2 (ie, 1/T2), and R2* (ie, 1/T2*) relaxation rates and quantitative susceptibility mapping; and 2) to investigate the associations among MR imaging, clinical scores, and cognitive measures of inhibitory control linked to basal ganglia functioning.Materials and methodsTwenty-nine patients with MS underwent a battery of neuropsychological tests including the Flanker and Stroop tasks. 7T MR imaging included 3D gradient-echo and single-echo multishot spin-echo EPI. Quantitative susceptibility mapping images were calculated by using a Wiener filter deconvolution algorithm. T2WI signal was normalized to CSF. R2 and R2* were calculated by log-linear regression. Average MR imaging metrics for the globus pallidus, putamen, and caudate were computed from manually traced ROIs including the largest central part of each structure.ResultsMarked spatial variation was consistently visualized on quantitative susceptibility mapping and T2/T2*WI within each basal ganglia structure. MR imaging metrics correlated with each other for each basal ganglia structure individually. Notably, caudate and putamen quantitative susceptibility mapping metrics were similar, but the putamen R2 was larger than the caudate R2. This finding suggests that tissue features contribute differently to R2 and quantitative susceptibility mapping. Caudate and anterior putamen quantitative susceptibility mapping correlated with the Flanker but not Stroop measures; R2 did not correlate with inhibitory control measures. Putamen quantitative susceptibility mapping and caudate and putamen R2 correlated with the Expanded Disability Status Scale.ConclusionsOur study showed that quantitative susceptibility mapping and R2 may be complementary indicators for basal ganglia tissue changes in MS. Our findings are consistent with the hypothesis that decreased performance of basal ganglia-reliant tasks involving inhibitory control is associated with increased quantitative susceptibility mapping.
| S-EPMC7960135 | biostudies-literature
Project description:The diagnosis of amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) is often difficult because of a lack of disease biomarkers. The purpose of this study was to investigate quantitative susceptibility mapping (QSM) of the motor cortex as a potential quantitative biomarker for the diagnosis of ALS and PLS.From a retrospective database, QSM images of 16 patients with upper motor neuron disease (nine men [56%], seven women; mean age, 56.3 years; 12 with ALS, four with PLS) and 23 control patients (13 men [56%], 10 women; mean age, 56.6 years) were reviewed. Two neuroradiologists, blinded to diagnosis, qualitatively assessed QSM, T2- and T2*-weighted, and T2-weighted FLAIR images. Relative motor cortex susceptibility was calculated by subtraction of adjacent white matter and CSF signal intensity from mean motor cortex susceptibility on the axial image most representative of the right- or left-hand lobule, and ROC analysis was performed. The Fisher exact and Student t tests were used to evaluate for statistical differences between the groups.Qualitatively, QSM had greater diagnostic accuracy than T2-weighted, T2*-weighted, or T2-weighted FLAIR imaging for the diagnosis of ALS and PLS. Quantitatively, relative motor cortex susceptibility was found to be significantly greater in patients with motor neuron disease than in control patients (46.0 and 35.0 ppb; p < 0.001). ROC analysis showed an AUC of 0.88 (p < 0.0001) and an optimal cutoff value of 40.5 ppb for differentiating control patients from patients with ALS or PLS (sensitivity, 87.5%; specificity, 87.0%).QSM is a sensitive and specific quantitative biomarker of iron deposition in the motor cortex in ALS and PLS.
| S-EPMC4889122 | biostudies-literature
Project description:PurposeQuantitative susceptibility mapping (QSM) is influenced by iron as well as myelin, which makes interpretation of pathologic changes challenging. Concurrent acquisition of MR sequences that are sensitive to axonal/myelin integrity, such as diffusion tensor imaging (DTI), may provide context for interpreting quantitative susceptibility (QS) signal. The purpose of our study was to investigate alterations in normal-appearing white matter (NAWM) in multiple sclerosis (MS) using QSM in conjunction with DTI.MethodsTwenty relapsing-remitting MS patients and 20 age-matched healthy controls (HC) were recruited for this prospective study. QS, radial diffusivity (RD), fractional anisotropy (FA), and R2* maps within the whole brain as well as individual tracts were generated for comparison between NAWM and HC white matter (HCWM).ResultsMS lesions demonstrated significant differences in QS, FA, RD, and R2* compared to HCWM (p < 0.03). These metrics did not show a significant difference between whole-brain NAWM and HCWM. Among NAWM tracts, the cingulate gyri demonstrated significantly decreased QS compared to HCWM (p = 0.004). The forceps major showed significant differences in FA and RD without corresponding changes in QS (p < 0.01).ConclusionWe found discordant changes in QSM and DTI metrics within the cingulate gyri and forceps major. This may potentially reflect the influence of paramagnetic substrates such as iron, which could be decreased along these NAWM tracts. Our results point to the potential role of QSM as a unique biomarker, although additional validation studies are needed.
| S-EPMC6415662 | biostudies-literature