Contributions
Abstract: P506
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Gray matter (GM) damage is present in multiple sclerosis (MS) patients, and involves both the cortical GM and sub-cortical deep GM (SDGM) structures. No multicentre studies have investigated differences in quantitative susceptibility mapping (QSM) of the SDGM structures between healthy controls (HC) and patients with relapsing multiple sclerosis (MS).
Objective: To investigate associations between QSM and clinical outcomes of disease severity in a multicentre study.
Methods: This is an ongoing, Phase IV, prospective, MRI-reader-blinded, longitudinal, two centres (USA and Australia) study that enrolled 44 MS patients and 34 age- and sex-matched HCs. The clinical and MRI assessments were performed at baseline, and are collected at 6, 12 and 24 months after initiation of the fingolimod treatment. The MRI is obtained at 3T MRI with standardized protocol between the two centres. The QSM images were reconstructed by unwrapping phase images with a best-path algorithm, background-field correction with V-SHARP and conversion to QSM using HEIDI. The volume of brain SDGM structures was also calculated.
Results: When adjusted for age, sex and centre, MS patients showed increased susceptibility in caudate (p=0.001) and decreased susceptibility in thalamus (p=0.003), and decreased thalamus (p=0.008) and putamen (p=0.02) volumes. In correlation analysis, increased disability in MS patients, as measured by Expanded Disability Status Scale (EDSS), was associated with increased susceptibility in the globus pallidus (r=0.63, p< 0.001), putamen (r=0.54, p< 0.001), total SDGM (r=0.55, p< 0.001) and caudate (r=0.34, p=0.032). The associations between the increased EDSS and decreased SDGM volumes were: globus pallidus (r=-0.48, p< 0.001), total SDGM (r=-0.37, p=0.015), putamen (r=-0.33, p=0.032) and caudate (r=-0.32, p=0.037). In regression analyses, using susceptibility and volumetric variables as the independent- and disability as dependent- measure, while adjusting for age and sex, increased susceptibility in the globus pallidus (Beta=0.5, p=0.004) and putamen (Beta=0.37, p=0.031) were the only variables associated with increased disability.
Conclusions: The measurement of QSM is feasible in a multicentre study. QSM is a novel MRI outcome that is better associated with increased disability than volumetric SDGM measures.
Disclosure:
Funding statement: This study was funded by the research grant from Novartis.
Robert Zivadinov received personal compensation from Teva Pharmaceuticals, Biogen Idec, EMD Serono, Genzyme-Sanofi, Claret Medical, IMS Health, and Novartis for speaking and consultant fees. He received financial support for research activities from Teva Pharmaceuticals, Genzyme-Sanofi, Novartis, Claret Medical, Intekrin-Coherus, and IMS Health.
Ferdinand Schweser, Caitlin Dawes, Jesper Hagemeier, Tim Wang, Niels Bergsland, Heidi Beadnall, Ellen Carl have nothing to disclose.
Bianca Weinstock- Guttman received honoraria as a speaker and as a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme&Sanofi, Novartis and Acorda. Dr Weinstock-Guttman received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme&Sanofi, Novartis, Acorda.
Ralph RH. Benedict has acted as a consultant or scientific advisory board member for Bayer, Biogen Idec, Actelion, and Novartis. He receives royalties from Psychological Assessment Resources, Inc. He has received financial support for research activities from Shire Pharmaceuticals, Accorda and Biogen Idec.
Michael Barnett has received institutional support for research, speaking and consulting activities from Biogen, Genzyme, Novartis, Teva and Roche; and travel support from Novartis and Biogen.
Abstract: P506
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Gray matter (GM) damage is present in multiple sclerosis (MS) patients, and involves both the cortical GM and sub-cortical deep GM (SDGM) structures. No multicentre studies have investigated differences in quantitative susceptibility mapping (QSM) of the SDGM structures between healthy controls (HC) and patients with relapsing multiple sclerosis (MS).
Objective: To investigate associations between QSM and clinical outcomes of disease severity in a multicentre study.
Methods: This is an ongoing, Phase IV, prospective, MRI-reader-blinded, longitudinal, two centres (USA and Australia) study that enrolled 44 MS patients and 34 age- and sex-matched HCs. The clinical and MRI assessments were performed at baseline, and are collected at 6, 12 and 24 months after initiation of the fingolimod treatment. The MRI is obtained at 3T MRI with standardized protocol between the two centres. The QSM images were reconstructed by unwrapping phase images with a best-path algorithm, background-field correction with V-SHARP and conversion to QSM using HEIDI. The volume of brain SDGM structures was also calculated.
Results: When adjusted for age, sex and centre, MS patients showed increased susceptibility in caudate (p=0.001) and decreased susceptibility in thalamus (p=0.003), and decreased thalamus (p=0.008) and putamen (p=0.02) volumes. In correlation analysis, increased disability in MS patients, as measured by Expanded Disability Status Scale (EDSS), was associated with increased susceptibility in the globus pallidus (r=0.63, p< 0.001), putamen (r=0.54, p< 0.001), total SDGM (r=0.55, p< 0.001) and caudate (r=0.34, p=0.032). The associations between the increased EDSS and decreased SDGM volumes were: globus pallidus (r=-0.48, p< 0.001), total SDGM (r=-0.37, p=0.015), putamen (r=-0.33, p=0.032) and caudate (r=-0.32, p=0.037). In regression analyses, using susceptibility and volumetric variables as the independent- and disability as dependent- measure, while adjusting for age and sex, increased susceptibility in the globus pallidus (Beta=0.5, p=0.004) and putamen (Beta=0.37, p=0.031) were the only variables associated with increased disability.
Conclusions: The measurement of QSM is feasible in a multicentre study. QSM is a novel MRI outcome that is better associated with increased disability than volumetric SDGM measures.
Disclosure:
Funding statement: This study was funded by the research grant from Novartis.
Robert Zivadinov received personal compensation from Teva Pharmaceuticals, Biogen Idec, EMD Serono, Genzyme-Sanofi, Claret Medical, IMS Health, and Novartis for speaking and consultant fees. He received financial support for research activities from Teva Pharmaceuticals, Genzyme-Sanofi, Novartis, Claret Medical, Intekrin-Coherus, and IMS Health.
Ferdinand Schweser, Caitlin Dawes, Jesper Hagemeier, Tim Wang, Niels Bergsland, Heidi Beadnall, Ellen Carl have nothing to disclose.
Bianca Weinstock- Guttman received honoraria as a speaker and as a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme&Sanofi, Novartis and Acorda. Dr Weinstock-Guttman received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme&Sanofi, Novartis, Acorda.
Ralph RH. Benedict has acted as a consultant or scientific advisory board member for Bayer, Biogen Idec, Actelion, and Novartis. He receives royalties from Psychological Assessment Resources, Inc. He has received financial support for research activities from Shire Pharmaceuticals, Accorda and Biogen Idec.
Michael Barnett has received institutional support for research, speaking and consulting activities from Biogen, Genzyme, Novartis, Teva and Roche; and travel support from Novartis and Biogen.