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  • 1
    In: Annals of Neurology, Wiley, Vol. 92, No. 3 ( 2022-09), p. 486-502
    Abstract: Neuropathological studies have shown that multiple sclerosis (MS) lesions are heterogeneous in terms of myelin/axon damage and repair as well as iron content. However, it remains a challenge to identify specific chronic lesion types, especially remyelinated lesions, in vivo in patients with MS. Methods We performed 3 studies: (1) a cross‐sectional study in a prospective cohort of 115 patients with MS and 76 healthy controls, who underwent 3 T magnetic resonance imaging (MRI) for quantitative susceptibility mapping (QSM), myelin water fraction (MWF), and neurite density index (NDI) maps. White matter (WM) lesions in QSM were classified into 5 QSM lesion types (iso‐intense, hypo‐intense, hyperintense, lesions with hypo‐intense rims, and lesions with paramagnetic rim legions [PRLs]); (2) a longitudinal study of 40 patients with MS to study the evolution of lesions over 2 years; (3) a postmortem histopathology‐QSM validation study in 3 brains of patients with MS to assess the accuracy of QSM classification to identify neuropathological lesion types in 63 WM lesions. Results At baseline, hypo‐ and isointense lesions showed higher mean MWF and NDI values compared to other QSM lesion types ( p   〈  0.0001). Further, at 2‐year follow‐up, hypo‐/iso‐intense lesions showed an increase in MWF. Postmortem analyses revealed that QSM highly accurately identifies (1) fully remyelinated areas as hypo‐/iso‐intense (sensitivity = 88.89% and specificity = 100%), (2) chronic inactive lesions as hyperintense (sensitivity = 71.43% and specificity = 92.00%), and (3) chronic active/smoldering lesions as PRLs (sensitivity = 92.86% and specificity = 86.36%). Interpretation These results provide the first evidence that it is possible to distinguish chronic MS lesions in a clinical setting, hereby supporting with new biomarkers to develop and assess remyelinating treatments. ANN NEUROL 2022;92:486–502
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2037912-2
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  • 2
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 97, No. 6 ( 2021-08-10), p. e543-e553
    Abstract: To assess whether chronic white matter inflammation in patients with multiple sclerosis (MS) as detected in vivo by paramagnetic rim MRI lesions (PRLs) is associated with higher serum neurofilament light chain (sNfL) levels, a marker of neuroaxonal damage. Methods In 118 patients with MS with no gadolinium-enhancing lesions or recent relapses, we analyzed 3D-submillimeter phase MRI and sNfL levels. Histopathologic evaluation was performed in 25 MS lesions from 20 additional autopsy MS cases. Results In univariable analyses, participants with ≥2 PRLs (n = 43) compared to those with ≤1 PRL (n = 75) had higher age-adjusted sNfL percentiles (median, 91 and 68; p 〈 0.001) and higher Multiple Sclerosis Severity Scale scores (MSSS median, 4.3 and 2.4; p = 0.003). In multivariable analyses, sNfL percentile levels were higher in PRLs ≥2 cases (β add , 16.3; 95% confidence interval [CI], 4.6–28.0; p 〈 0.01), whereas disease-modifying treatment (DMT), Expanded Disability Status Scale (EDSS) score, and T2 lesion load did not affect sNfL. In a similar model, sNfL percentile levels were highest in cases with ≥4 PRLs (n = 30; β add , 30.4; 95% CI, 15.6–45.2; p 〈 0.01). Subsequent multivariable analysis revealed that PRLs ≥2 cases also had higher MSSS (β add , 1.1; 95% CI, 0.3–1.9; p 〈 0.01), whereas MSSS was not affected by DMT or T2 lesion load. On histopathology, both chronic active and smoldering lesions exhibited more severe acute axonal damage at the lesion edge than in the lesion center (edge vs center: p = 0.004 and p = 0.0002, respectively). Conclusion Chronic white matter inflammation was associated with increased levels of sNfL and disease severity in nonacute MS, suggesting that PRL contribute to clinically relevant, inflammation-driven neurodegeneration.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 3
    In: NMR in Biomedicine, Wiley, Vol. 35, No. 8 ( 2022-08)
    Abstract: Manually segmenting multiple sclerosis (MS) cortical lesions (CLs) is extremely time consuming, and past studies have shown only moderate inter‐rater reliability. To accelerate this task, we developed a deep‐learning‐based framework (CLAIMS: Cortical Lesion AI‐Based Assessment in Multiple Sclerosis) for the automated detection and classification of MS CLs with 7 T MRI. Two 7 T datasets, acquired at different sites, were considered. The first consisted of 60 scans that include 0.5 mm isotropic MP2RAGE acquired four times (MP2RAGE×4), 0.7 mm MP2RAGE, 0.5 mm  T 2 *‐weighted GRE, and 0.5 mm  T 2 *‐weighted EPI. The second dataset consisted of 20 scans including only 0.75 × 0.75 × 0.9 mm 3 MP2RAGE. CLAIMS was first evaluated using sixfold cross‐validation with single and multi‐contrast 0.5 mm MRI input. Second, the performance of the model was tested on 0.7 mm MP2RAGE images after training with either 0.5 mm MP2RAGE×4, 0.7 mm MP2RAGE, or alternating the two. Third, its generalizability was evaluated on the second external dataset and compared with a state‐of‐the‐art technique based on partial volume estimation and topological constraints (MSLAST). CLAIMS trained only with MP2RAGE×4 achieved results comparable to those of the multi‐contrast model, reaching a CL true positive rate of 74% with a false positive rate of 30%. Detection rate was excellent for leukocortical and subpial lesions (83%, and 70%, respectively), whereas it reached 53% for intracortical lesions. The correlation between disability measures and CL count was similar for manual and CLAIMS lesion counts. Applying a domain‐scanner adaptation approach and testing CLAIMS on the second dataset, the performance was superior to MSLAST when considering a minimum lesion volume of 6 μL (lesion‐wise detection rate of 71% versus 48%). The proposed framework outperforms previous state‐of‐the‐art methods for automated CL detection across scanners and protocols. In the future, CLAIMS may be useful to support clinical decisions at 7 T MRI, especially in the field of diagnosis and differential diagnosis of MS patients.
    Type of Medium: Online Resource
    ISSN: 0952-3480 , 1099-1492
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2002003-X
    detail.hit.zdb_id: 1000976-0
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  • 4
    In: Investigative Radiology, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 6 ( 2019-6), p. 356-364
    Abstract: The aim of this study was to develop a new automated segmentation method of white matter (WM) and cortical multiple sclerosis (MS) lesions visible on magnetization-prepared 2 inversion-contrast rapid gradient echo (MP2RAGE) images acquired at 7 T MRI. Materials and Methods The proposed prototype (MSLAST [Multiple Sclerosis Lesion Analysis at Seven Tesla]) takes as input a single image contrast derived from the 7T MP2RAGE prototype sequence and is based on partial volume estimation and topological constraints. First, MSLAST performs a skull-strip of MP2RAGE images and computes tissue concentration maps for WM, gray matter (GM), and cerebrospinal fluid (CSF) using a partial volume model of tissues within each voxel. Second, MSLAST performs (1) connected-component analysis to GM and CSF concentration maps to classify small isolated components as MS lesions; (2) hole-filling in the WM concentration map to classify areas with low WM concentration surrounded by WM (ie, MS lesions); and (3) outlier rejection to the WM mask to improve the classification of small WM lesions. Third, MSLAST unifies the 3 maps obtained from 1, 2, and 3 processing steps to generate a global lesion mask. Results Quantitative and qualitative assessments were performed using MSLAST in 25 MS patients from 2 research centers. Overall, MSLAST detected a median of 71% of MS lesions, specifically 74% of WM and 58% of cortical lesions, when a minimum lesion size of 6 μL was considered. The median false-positive rate was 40%. When a 15 μL minimal lesions size was applied, which is the approximation of the minimal size recommended for 1.5/3 T images, the median detection rate was 80% for WM and 63% for cortical lesions, respectively, and the median false-positive rate was 33%. We observed high correlation between MSLAST and manual segmentations (Spearman rank correlation coefficient, ρ = 0.91), although MSLAST underestimated the total lesion volume (average difference of 1.1 mL), especially in patients with high lesion loads. MSLAST also showed good scan-rescan repeatability within the same session with an average absolute volume difference and F1 score of 0.38 ± 0.32 mL and 84%, respectively. Conclusions We propose a new methodology to facilitate the segmentation of WM and cortical MS lesions at 7 T MRI, our approach uses a single MP2RAGE scan and may be of special interest to clinicians and researchers.
    Type of Medium: Online Resource
    ISSN: 1536-0210 , 0020-9996
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2041543-6
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  • 5
    In: NeuroImage: Clinical, Elsevier BV, Vol. 28 ( 2020), p. 102412-
    Type of Medium: Online Resource
    ISSN: 2213-1582
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2701571-3
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  • 6
    In: Brain, Oxford University Press (OUP), Vol. 144, No. 6 ( 2021-07-28), p. 1684-1696
    Abstract: Damage to the myelin sheath and the neuroaxonal unit is a cardinal feature of multiple sclerosis; however, a detailed characterization of the interaction between myelin and axon damage in vivo remains challenging. We applied myelin water and multi-shell diffusion imaging to quantify the relative damage to myelin and axons (i) among different lesion types; (ii) in normal-appearing tissue; and (iii) across multiple sclerosis clinical subtypes and healthy controls. We also assessed the relation of focal myelin/axon damage with disability and serum neurofilament light chain as a global biological measure of neuroaxonal damage. Ninety-one multiple sclerosis patients (62 relapsing-remitting, 29 progressive) and 72 healthy controls were enrolled in the study. Differences in myelin water fraction and neurite density index were substantial when lesions were compared to healthy control subjects and normal-appearing multiple sclerosis tissue: both white matter and cortical lesions exhibited a decreased myelin water fraction and neurite density index compared with healthy (P  & lt; 0.0001) and peri-plaque white matter (P  & lt; 0.0001). Periventricular lesions showed decreased myelin water fraction and neurite density index compared with lesions in the juxtacortical region (P  & lt; 0.0001 and P  & lt; 0.05). Similarly, lesions with paramagnetic rims showed decreased myelin water fraction and neurite density index relative to lesions without a rim (P  & lt; 0.0001). Also, in 75% of white matter lesions, the reduction in neurite density index was higher than the reduction in the myelin water fraction. Besides, normal-appearing white and grey matter revealed diffuse reduction of myelin water fraction and neurite density index in multiple sclerosis compared to healthy controls (P  & lt; 0.01). Further, a more extensive reduction in myelin water fraction and neurite density index in normal-appearing cortex was observed in progressive versus relapsing-remitting participants. Neurite density index in white matter lesions correlated with disability in patients with clinical deficits (P  & lt; 0.01, beta = −10.00); and neurite density index and myelin water fraction in white matter lesions were associated to serum neurofilament light chain in the entire patient cohort (P  & lt; 0.01, beta = −3.60 and P  & lt; 0.01, beta = 0.13, respectively). These findings suggest that (i) myelin and axon pathology in multiple sclerosis is extensive in both lesions and normal-appearing tissue; (ii) particular types of lesions exhibit more damage to myelin and axons than others; (iii) progressive patients differ from relapsing-remitting patients because of more extensive axon/myelin damage in the cortex; and (iv) myelin and axon pathology in lesions is related to disability in patients with clinical deficits and global measures of neuroaxonal damage.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 7
    In: NeuroImage: Clinical, Elsevier BV, Vol. 36 ( 2022), p. 103205-
    Type of Medium: Online Resource
    ISSN: 2213-1582
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2701571-3
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