Contributions
Abstract: P520
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Quantitative susceptibility mapping (QSM) is a novel MRI technique that can provide increased specificity in iron detection or changes of myelin. Previous research using a variety of MRI iron and myelin sensitive methods has shown that multiple sclerosis (MS) patients tend to have more severe demyelination and iron deposition, especially in the deep gray matter (DGM) and thalamus, in particular. However, no previous studies explored association between QSM and disability in MS patients.
Objective: We explored association of QSM in DGM and disability, as measured by Expanded Disability Status Scale (EDSS) in a large cohort of MS patients.
Methods: 600 MS patients (relapsing-remitting (RR): 452, secondary-progressive: 148) and 250 age- and sex-matched healthy controls (HCs) were recruited for the present study. QSM magnetic susceptibility was determined for DGM structures with higher susceptibility representing increased iron levels and lower susceptibility representing decreased iron levels. Associations of QSM with clinical outcomes were explored using regression analysis in which susceptibility of DGM structures was used as dependent variable, age and sex, as covariates, MS course (RR vs. SP), EDSS and disease duration, as variables of interest, and interaction effect to test whether relationship between EDSS and disease duration with QSM measures varies between RR and SP.
Results: MS patients showed increased susceptibility in the caudate, putamen and globus pallidus (p< 0.001) and total DGM (p=0.003) and decreased in thalamus (p< 0.001) compared to HCs. SPMS patients showed decreased susceptibility in thalamus compared to RRMS (p=0.007). Decreased susceptibility of thalamus was significantly associated with longer disease duration (p=0.001), increased disability (p=0.006) and SPMS course (p=0.024). The interaction effect between QSM and disease duration showed that longer disease duration in RRMS was associated with decreased susceptibility of the thalamus. Additional significant relationships were found between increased susceptibility in the globus pallidus (p=0.004) and hippocampus (p=0.017) and increased disability.
Conclusions: These findings suggest that decreased susceptibility of the thalamus is strongly associated with more severe disability, longer disease duration and SPMS course. The QSM changes of the thalamus may be also related to structural changes of the myelin and should be investigated in longitudinal studies.
Disclosure: 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 and IMS Health.
Jesper Hagemeier, Ellen Carl, Fuchun Li, Niels Bergsland, Deepa Ramasamy, Jacqueline Durfee and Ferdinand Schweser have nothing to disclose.
Channa Kolb has received speaker honoraria from Novartis, Genzyme and Biogen-Idec.
Michael G Dwyer received personal compensation from Novartis and Claret Medical for speaking and consultant fees. He received financial support for research activities from Novartis.
David Hojnacki has received speaker honoraria and consultant fees from Biogen Idec, Teva Pharmaceutical Industries Ltd., EMD Serono, Pfizer Inc, and Novartis.
Bianca Weinstock- Guttman has participated in speaker´s bureaus and served as a consultant for Biogen Idec, Teva Neuroscience, EMD Serono, Novartis, Genzyme & Sanofi, Mylan Inc., and Acorda Therapeutics, Inc. Dr. Weinstock-Guttman also has received grant/research support from the agencies listed in the previous sentence as well as Questcor Pharmaceuticals, Inc., and Shire. She serves in the editorial board for BMC Neurology, Journal of International MS, Journal of Multiple Sclerosis.
Abstract: P520
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Quantitative susceptibility mapping (QSM) is a novel MRI technique that can provide increased specificity in iron detection or changes of myelin. Previous research using a variety of MRI iron and myelin sensitive methods has shown that multiple sclerosis (MS) patients tend to have more severe demyelination and iron deposition, especially in the deep gray matter (DGM) and thalamus, in particular. However, no previous studies explored association between QSM and disability in MS patients.
Objective: We explored association of QSM in DGM and disability, as measured by Expanded Disability Status Scale (EDSS) in a large cohort of MS patients.
Methods: 600 MS patients (relapsing-remitting (RR): 452, secondary-progressive: 148) and 250 age- and sex-matched healthy controls (HCs) were recruited for the present study. QSM magnetic susceptibility was determined for DGM structures with higher susceptibility representing increased iron levels and lower susceptibility representing decreased iron levels. Associations of QSM with clinical outcomes were explored using regression analysis in which susceptibility of DGM structures was used as dependent variable, age and sex, as covariates, MS course (RR vs. SP), EDSS and disease duration, as variables of interest, and interaction effect to test whether relationship between EDSS and disease duration with QSM measures varies between RR and SP.
Results: MS patients showed increased susceptibility in the caudate, putamen and globus pallidus (p< 0.001) and total DGM (p=0.003) and decreased in thalamus (p< 0.001) compared to HCs. SPMS patients showed decreased susceptibility in thalamus compared to RRMS (p=0.007). Decreased susceptibility of thalamus was significantly associated with longer disease duration (p=0.001), increased disability (p=0.006) and SPMS course (p=0.024). The interaction effect between QSM and disease duration showed that longer disease duration in RRMS was associated with decreased susceptibility of the thalamus. Additional significant relationships were found between increased susceptibility in the globus pallidus (p=0.004) and hippocampus (p=0.017) and increased disability.
Conclusions: These findings suggest that decreased susceptibility of the thalamus is strongly associated with more severe disability, longer disease duration and SPMS course. The QSM changes of the thalamus may be also related to structural changes of the myelin and should be investigated in longitudinal studies.
Disclosure: 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 and IMS Health.
Jesper Hagemeier, Ellen Carl, Fuchun Li, Niels Bergsland, Deepa Ramasamy, Jacqueline Durfee and Ferdinand Schweser have nothing to disclose.
Channa Kolb has received speaker honoraria from Novartis, Genzyme and Biogen-Idec.
Michael G Dwyer received personal compensation from Novartis and Claret Medical for speaking and consultant fees. He received financial support for research activities from Novartis.
David Hojnacki has received speaker honoraria and consultant fees from Biogen Idec, Teva Pharmaceutical Industries Ltd., EMD Serono, Pfizer Inc, and Novartis.
Bianca Weinstock- Guttman has participated in speaker´s bureaus and served as a consultant for Biogen Idec, Teva Neuroscience, EMD Serono, Novartis, Genzyme & Sanofi, Mylan Inc., and Acorda Therapeutics, Inc. Dr. Weinstock-Guttman also has received grant/research support from the agencies listed in the previous sentence as well as Questcor Pharmaceuticals, Inc., and Shire. She serves in the editorial board for BMC Neurology, Journal of International MS, Journal of Multiple Sclerosis.