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  • 1
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    Online Resource
    The Role of High‐Frequency MRI Monitoring in the Detection of Brain Atrophy in Multiple Sclerosis
    Wiley ; 2018
    In:  Journal of Neuroimaging Vol. 28, No. 3 ( 2018-05), p. 328-337
    Details
    In: Journal of Neuroimaging, Wiley, Vol. 28, No. 3 ( 2018-05), p. 328-337
    Abstract: A relatively high intraindividual variability of longitudinal magnetic resonance imaging (MRI) of brain volume loss (BVL) measurements over time renders challenging its application to individual multiple sclerosis (MS) patients. Objective of this study was to investigate if high‐frequency brain MRI monitoring affects identification of pathological BVL in an individual patient. METHODS One hundred fifty‐seven relapsing‐remitting MS patients had seven MRI scans over 12 months follow‐up. All 1,585 MRI scans were performed on the same 1.5T scanner using an identical scanning protocol. Volumetric analysis was performed by ScanView and SIENA software. Linear regression analysis was used for estimation of annualized BVL, with a cutoff greater than .4% defined as pathological. We compared proportions of patients with pathological BVL obtained by analysis of different number of MRI time‐points. RESULTS An analysis of seven MRI scans (months 0, 2, 4, 6, 8, 10, and 12) showed pathological BVL in 105 (65%) of patients. When three MRI scans were included (months 0, 6, and 12), we found 10 (6.4%) false negative and 9 (5.7%) false positive results compared with the analysis of seven MRI scans, used as a reference for assessment of pathological BVL. Analysis of two MRI time‐points (months 0 and 12) showed 10 (6.4%) false negative and 13 (8.3%) false positive results compared with analysis of seven MRI time‐points. Change in the accuracy of pathological BVL between results obtained by analysis of seven and two time‐points was 14.7%. CONCLUSIONS High‐frequency MRI monitoring may have a considerable effect on improving the precision of precisely identifying pathological BVL in individual patients. However, limitations in translation to clinical practice remain.
    Type of Medium: Online Resource
    ISSN: 1051-2284 , 1552-6569
    URL: Issue
    URL: Article
    DOI: 10.1111/jon.2018.28.issue-3
    DOI: 10.1111/jon.12505
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2035400-9
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  • 2
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    Atrophied Brain Lesion Volume: A New Imaging Biomarker in Multiple Sclerosis
    Wiley ; 2018
    In:  Journal of Neuroimaging Vol. 28, No. 5 ( 2018-09), p. 490-495
    Details
    In: Journal of Neuroimaging, Wiley, Vol. 28, No. 5 ( 2018-09), p. 490-495
    Abstract: Lesion accrual in multiple sclerosis (MS) is an important and clinically relevant measure, used extensively as an imaging trial endpoint. However, lesions may also shrink or disappear entirely due to atrophy. Although generally ignored or treated as a nuisance, this phenomenon may actually be an important stand‐alone imaging biomarker. Therefore, we investigated the rate of brain lesion loss due to atrophy (atrophied lesion volume) in MS subtypes compared to baseline lesion volume and to new and enlarging lesion volumes, and evaluated the independent predictive value of this phenomenon for clinical disability. METHODS A total of 192 patients (18 clinically isolated syndrome, 126 relapsing‐remitting MS, and 48 progressive) received 3T magnetic resonance imaging at baseline and 5 years. Lesions were quantified at baseline, and new/enlarging lesion volumes were calculated over the study interval. Atrophied lesion volume was calculated by combining baseline lesion masks with follow‐up SIENAX‐derived cerebrospinal fluid partial volume maps. Measures were compared between disease subgroups, and correlations with disability change (Expanded Disability Status Scale [EDSS]) were evaluated. Hierarchical regression was employed to determine the unique additive value of atrophied lesion volume. RESULTS Atrophied lesion volume was different between MS subtypes ( P = .02), and exceeded new lesion volume accumulation in progressive MS (298.1 vs. 75.5 mm 3 ). Atrophied lesion volume was the only significant correlate of EDSS change ( r = .192 relapsing, r = .317 progressive, P 〈 .05), and explained significant additional variance when controlling for brain atrophy and new/enlarging lesion volume ( R 2 .092 vs. .045, P = .003). CONCLUSION Atrophied lesion volume is a unique and clinically relevant imaging marker in MS, with particular promise in progressive MS.
    Type of Medium: Online Resource
    ISSN: 1051-2284 , 1552-6569
    URL: Issue
    URL: Article
    DOI: 10.1111/jon.2018.28.issue-5
    DOI: 10.1111/jon.12527
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2035400-9
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  • 3
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    MRI‐based thalamic volumetry in multiple sclerosis using FSL‐FIRST: Systematic assessment of common error modes
    Wiley ; 2022
    In:  Journal of Neuroimaging Vol. 32, No. 2 ( 2022-03), p. 245-252
    Details
    In: Journal of Neuroimaging, Wiley, Vol. 32, No. 2 ( 2022-03), p. 245-252
    Abstract: FSL's FMRIB's Integrated Registration and Segmentation Tool (FSL‐FIRST) is a widely used and well‐validated tool. Automated thalamic segmentation is a common application and an important longitudinal measure for multiple sclerosis (MS). However, FSL‐FIRST's algorithm is based on shape models derived from non‐MS groups. As such, the present study sought to systematically assess common thalamic segmentation errors made by FSL‐FIRST on MRIs from people with multiple sclerosis (PwMS). Methods FSL‐FIRST was applied to generate thalamic segmentation masks for 890 MR images in PwMS. Images and masks were reviewed systematically to classify and quantify errors, as well as associated anatomical variations and MRI abnormalities. For cases with overt errors ( n = 362), thalamic masks were corrected and quantitative volumetric differences were calculated. Results In the entire quantitative volumetric group, the mean volumetric error of FSL‐FIRST was 2.74% (0.360 ml): among only corrected cases, the mean volumetric error was 6.79% (0.894 ml). The average percent volumetric error associated with seven error types, two anatomical variants, and motions artifacts are reported. Additional analyses showed that the presence of motion artifacts or anatomical variations significantly increased the probability of error ( χ 2  = 18.14, p   〈  .01 and χ 2  = 64.89, p   〈  .001, respectively). Finally, thalamus volume error was negatively associated with degree of atrophy, such that smaller thalami were systematically overestimated ( r = –.28, p   〈  .001). Conclusions In PwMS, FSL‐FIRST thalamic segmentation miscalculates thalamic volumetry in a predictable fashion, and may be biased to overestimate highly atrophic thalami. As such, it is recommended that segmentations be reviewed and corrected manually when appropriate for specific studies.
    Type of Medium: Online Resource
    ISSN: 1051-2284 , 1552-6569
    URL: Issue
    URL: Article
    DOI: 10.1111/jon.v32.2
    DOI: 10.1111/jon.12947
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2035400-9
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  • 4
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    Multisite MRI reproducibility of lateral ventricular volume using the NAIMS cooperative pilot dataset
    Wiley ; 2022
    In:  Journal of Neuroimaging Vol. 32, No. 5 ( 2022-09), p. 910-919
    Details
    In: Journal of Neuroimaging, Wiley, Vol. 32, No. 5 ( 2022-09), p. 910-919
    Abstract: The North American Imaging in Multiple Sclerosis (NAIMS) multisite project identified interscanner reproducibility issues with T1‐based whole brain volume (WBV). Lateral ventricular volume (LVV) acquired on T2‐fluid‐attenuated inverse recovery (FLAIR) scans has been proposed as a robust proxy measure. Therefore, we sought to determine the relative magnitude of scanner‐induced T2‐FLAIR‐based LVV and T1‐based WBV measurement errors in relation to clinically meaningful changes. Methods This was a post hoc analysis of the NAIMS pilot dataset in which a relapsing‐remitting MS patient with no intrastudy clinical or radiological activity was imaged twice on seven different Siemens scanners across the United States. LVV was determined using the automated NeuroSTREAM technique on T2‐FLAIR and WBV was determined with SIENAX on high‐resolution T1‐MPRAGE. Average LVV and WBV were measured, and absolute intrascanner and interscanner coefficients of variation (CoVs) were calculated. The variabilities were compared to previously established annual pathological and clinically meaningful cutoffs of 0.40% for WBV and of 3.51% for LVV. Results Mean LVV across all seven scan/rescan pairs was 45.87 ± 1.15 ml. Average LVV intrascanner CoV was 1.42% and interscanner CoV was 1.78%, both smaller than the reported annualized clinically meaningful cutoff of 3.51%. In contrast, intra‐ and interscanner CoVs for WBV (0.99% and 1.15%) were both higher than the established cutoff of 0.40%. Individually, 1/7 intrasite and 2/7 intersite pair‐wise LVV comparisons were above the 3.51% cutoff, whereas 4/7 intrasite and 7/7 intersite WBV comparisons were above the 0.40% cutoff. Conclusion Fully automated LVV segmentation has higher absolute variability than WBV, but much lower relative variability compared to clinically relevant changes, and may therefore be a meaningful proxy outcome measure of neurodegeneration.
    Type of Medium: Online Resource
    ISSN: 1051-2284 , 1552-6569
    URL: Issue
    URL: Article
    DOI: 10.1111/jon.v32.5
    DOI: 10.1111/jon.12998
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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  • 5
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    Application of hidden Markov random field approach for quantification of perfusion/diffusion mismatch in acute ischemic stroke
    Informa UK Limited ; 2008
    In:  Neurological Research Vol. 30, No. 8 ( 2008-10), p. 827-834
    Details
    In: Neurological Research, Informa UK Limited, Vol. 30, No. 8 ( 2008-10), p. 827-834
    Type of Medium: Online Resource
    ISSN: 0161-6412 , 1743-1328
    URL: Article
    DOI: 10.1179/174313208X340987
    RVK:
    XA 10000
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2008
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  • 6
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    Pathological cut-offs of global and regional brain volume loss in multiple sclerosis
    SAGE Publications ; 2019
    In:  Multiple Sclerosis Journal Vol. 25, No. 4 ( 2019-04), p. 541-553
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 25, No. 4 ( 2019-04), p. 541-553
    Abstract: Volumetric MRI surrogate markers of disease progression are lacking. Objective: To establish cut-off values of brain volume loss able to discriminate between healthy controls and MS patients. Methods: In total, 386 patients after first demyelinating event suggestive of MS (CIS), 964 relapsing-remitting MS (RRMS) patients, 63 secondary-progressive MS (SPMS) patients and 58 healthy controls were included in this longitudinal study. A total of 11,438 MRI scans performed on the same MRI scanner with the same protocol were analysed. Annualised percentage changes of whole brain, grey matter, thalamus and corpus callosum volumes were estimated. We investigated cut-offs able to discriminate between healthy controls and MS patients. Results: At a predefined specificity of 90%, the annualised percentage change cut-off of corpus callosum volume (−0.57%) was able to distinguish between healthy controls and patients with the highest sensitivity (51% in CIS, 48% in RRMS and 42% in SPMS patients). Lower sensitivities (22%−49%) were found for cut-offs of whole brain, grey matter and thalamic volume loss. Among CIS and RRMS patients, cut-offs were associated with greater accumulation of disability. Conclusion: We identified cut-offs of annualised global and regional brain volume loss rates able to discriminate between healthy controls and MS patients.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458517742739
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2019
    detail.hit.zdb_id: 2008225-3
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  • 7
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    Trait Conscientiousness predicts rate of brain atrophy in multiple sclerosis
    SAGE Publications ; 2020
    In:  Multiple Sclerosis Journal Vol. 26, No. 11 ( 2020-10), p. 1433-1436
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 26, No. 11 ( 2020-10), p. 1433-1436
    Abstract: Conscientiousness is a core personality trait with favorable prognosis in neuropsychiatric disease. Objective: We aimed to determine whether baseline Conscientiousness predicts future brain atrophy in multiple sclerosis (MS) after accounting for demographic and basic clinical characteristics. Methods: Trait Conscientiousness, clinical features, and Expanded Disability Status Scale (EDSS) were obtained at baseline. Lateral ventricle volume (LVV) was measured longitudinally. In a retrospective general linear mixed effects model, data from 424 patients were analyzed (mean 6 time-points, up to 15 years). Results/Conclusion: We observed significant age and Conscientiousness by time-from-baseline interactions indicating that younger age and higher Conscientiousness are associated with reduced progression of brain atrophy.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458519858605
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
    detail.hit.zdb_id: 2008225-3
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  • 8
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    Measurement of neurofilaments improves stratification of future disease activity in early multiple sclerosis
    SAGE Publications ; 2021
    In:  Multiple Sclerosis Journal Vol. 27, No. 13 ( 2021-11), p. 2001-2013
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 27, No. 13 ( 2021-11), p. 2001-2013
    Abstract: The added value of neurofilament light chain levels in serum (sNfL) to the concept of no evidence of disease activity-3 (NEDA-3) has not yet been investigated in detail. Objective: To assess whether combination of sNfL with NEDA-3 status improves identification of patients at higher risk of disease activity during the following year. Methods: We analyzed 369 blood samples from 155 early relapsing-remitting MS patients on interferon beta-1a. We compared disease activity, including the rate of brain volume loss in subgroups defined by NEDA-3 status and high or low sNfL ( 〉  90th or  〈  90th percentile). Results: In patients with disease activity (EDA-3), those with higher sNFL had higher odds of EDA-3 in the following year than those with low sNFL (86.5% vs 57.9%; OR = 4.25, 95% CI: [2.02, 8.95]; p = 0.0001) and greater whole brain volume loss during the following year (β = −0.36%; 95% CI = [−0.60, −0.13] ; p = 0.002). Accordingly, NEDA-3 patients with high sNfL showed numerically higher disease activity (EDA-3) in the following year compared with those with low sNfL (57.1% vs 31.1%). Conclusion: sNfL improves the ability to identify patients at higher risk of future disease activity, beyond their NEDA-3 status. Measurement of sNfL may assist clinicians in decision-making by providing more sensitive prognostic information.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/13524585211047977
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
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  • 9
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    A serial 10-year follow-up study of brain atrophy and disability progression in RRMS patients
    SAGE Publications ; 2016
    In:  Multiple Sclerosis Journal Vol. 22, No. 13 ( 2016-11), p. 1709-1718
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 22, No. 13 ( 2016-11), p. 1709-1718
    Abstract: We explored the evolution of brain atrophy in relation to development of confirmed disability progression (CDP) on serial 1.5T magnetic resonance imaging (MRI) scans over a 10-year period in 181 patients with early relapsing–remitting multiple sclerosis (RRMS). Methods: At 10-year follow-up, they were divided into those with (100) or without (76) CDP (confirmed after 48 weeks). Changes in whole brain (WB), cortical, gray matter (GM), white matter, and ventricular cerebrospinal fluid (vCSF) volumes were calculated on three-dimensional T1-weighted (3D-T1) scans between all available time points. Results: In multiple sclerosis (MS) patients with CDP compared to those without, the greatest effect size percentage volume change from baseline to follow-up was detected for WB ( d = 0.55, −7.5% vs −5.2%, p  〈  0.001), followed by vCSF ( d = 0.51, +41.1% vs +25.7%, p  〈  0.001), cortical ( d = 0.49, −7.7% vs −6.2%, p = 0.001), and GM ( d = 0.40, −7.1% vs −5.8%, p = 0.006) volumes. Mixed-effects model analysis, adjusted for age, sex, and treatment change, showed significant interactions between CDP status and percentage changes for WB and vCSF ( p  〈  0.001), cortical ( p = 0.02), and GM ( p = 0.04) volumes. Conclusions: WB and cortical atrophy, and enlargement of vCSF spaces are associated with development of CDP on serial yearly MRI assessments over a period of 10 years.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458516629769
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
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  • 10
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    Ventral posterior substantia nigra iron increases over 3 years in Parkinson's disease
    Wiley ; 2019
    In:  Movement Disorders Vol. 34, No. 7 ( 2019-07), p. 1006-1013
    Details
    In: Movement Disorders, Wiley, Vol. 34, No. 7 ( 2019-07), p. 1006-1013
    Abstract: Parkinson's disease (PD) is characterized in part by the progressive accumulation of iron within the substantia nigra (SN); however, its spatial and temporal dynamics remain relatively poorly understood. Objectives The objective of this study was to investigate spatial patterns and temporal evolution of SN iron accumulation in PD. Methods A total of 18 PD patients (mean disease duration = 6.2 years) receiving dopaminergic therapy and 16 healthy controls were scanned with 3T MRI at baseline and 3 years later using quantitative susceptibility mapping, an indirect marker of iron content. Iron was assessed separately in the posterior SN and anterior SN at the ventral and dorsal levels of the SN. The results were corrected for the false discovery rate. Results A significant group effect was found for the ventral posterior SN ( P   〈  .001) and anterior SN ( P = .042) quantitative susceptibility mapping as well as significant group x time interaction effects ( P = .02 and P = .043, respectively). In addition, a significant intragroup change during 3 years of follow‐up was found only in the ventral posterior SN of PD ( P = .012), but not healthy controls. No significant effects were detected for any dorsal SN measures. No associations were identified with clinical measures. Conclusions We found both cross‐sectional and longitudinal SN iron changes to be confined to its more ventral location in PD. Because pathology studies also show the ventral SN to degenerate early and to the greatest extent in PD, the assessment of iron levels by quantitative susceptibility mapping in this area may potentially represent a disease progression biomarker in PD. © 2019 International Parkinson and Movement Disorder Society
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
    URL: Article
    DOI: 10.1002/mds.v34.7
    DOI: 10.1002/mds.27730
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2041249-6
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