Contributions
Abstract: P1025
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Although gray matter (GM) involvement is now widely recognized as a hallmark of MS, the spatial relationships of GM atrophy in disparate areas throughout the brain remain poorly understood. Multivariate, data-driven approaches offer a means to investigate atrophy patterns while combining information from multiple voxels, unlike traditional methods such as voxel-based morphometry (VBM). However, such techniques have yet to be used extensively in MS and no longitudinal studies exist.
Objectives: To investigate the spatial patterns of GM atrophy in a longitudinal setting.
Methods: 152 early RRMS patients (mean disease duration of 5 years) were scanned on the same MRI scanner with the same 3D T1 protocol at baseline and at 10 years. At 10-year follow-up, they were divided into those with confirmed disability progression (CDP) (85) or without (67) CDP, by standard treatment trial criteria. An optimized, longitudinal source-based morphometry (SBM) pipeline was implemented via a combination of VBM and independent component analysis (ICA) techniques. SBM was used to identify patterns of spatially distinct regions of GM atrophy with common covariation over 10 years in the entire cohort of patients. Next, differences in the loading factors obtained using ICA were compared between patients with CDP and without, while controlling for age and sex. Significance was set at p < 0.05.
Results: 20 components were estimated using ICA. The patterns are similar to those observed using resting state functional MRI, particularly as regards to the default mode and salience networks. Most relevant patterns included: 1) bilateral deep GM (including thalamus caudate, globus pallidus and putamen) and frontal cortex; 2) cerebellum; 3) bilateral thalamus, bilateral caudate and bilateral insular cortex; 4) cingulate cortex. Patients with CDP demonstrated greater atrophy in 2 of the identified patterns (Pattern 1: bilateral thalamus, bilateral precuneous and bilateral sensorimotor (p=.007); Pattern 2: bilateral hippocampi, bilateral temporal, bilateral frontal, bilateral anterior cingulate (p=.024)).
Conclusions: To the best of our knowledge, this is the first longitudinal study in MS showing that the development of GM atrophy progresses in a coherent manner between anatomically and functionally related areas. Longitudinal SBM offers a novel method to better characterize the spatial relationship of GM atrophy and disability than is possible using traditional methods.
Disclosure:
Study Disclosures:
The study is an investigator-initiated study that was supported by Czech Ministries of Education and Health [NT13237-4/2012, PRVOUK-P26/LF1/4, RVO-VFN64165/2012]. The MRI acquisition part of the study was supported by Gedeon Richter and Biogen Idec. The MRI analysis part was supported in part by Biogen Idec.
Financial Relationships/Potential Conflicts of Interest:
Dr. Bergsland has nothing to disclose.
Dr. Horakova received compensation for travel, speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck Serono, Bayer Shering, and Teva, as well as support for research activities from Biogen Idec.
Dr. Dwyer has received personal compensation from Claret Medical and EMD Serono, and research grant support from Novartis.
Dr. Uher received financial support for conference travel and honoraria from Biogen Idec, Novartis, Merck Serono and Genzyme.
Dr. Tyblova received compensation for travel and honoraria from Biogen Idec, Sanofi Aventis, Teva and Merck Serono.
Drs. Seidl, Vaneckova, and Krasensky received financial support for research activities from Biogen Idec.
Dr. Havrdova received speaker honoraria and consultant fees from Actelion, Biogen Idec, Merck Serono, Novartis, Receptos, Sanofi Genzyme, and Merck Serono
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.
Abstract: P1025
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Although gray matter (GM) involvement is now widely recognized as a hallmark of MS, the spatial relationships of GM atrophy in disparate areas throughout the brain remain poorly understood. Multivariate, data-driven approaches offer a means to investigate atrophy patterns while combining information from multiple voxels, unlike traditional methods such as voxel-based morphometry (VBM). However, such techniques have yet to be used extensively in MS and no longitudinal studies exist.
Objectives: To investigate the spatial patterns of GM atrophy in a longitudinal setting.
Methods: 152 early RRMS patients (mean disease duration of 5 years) were scanned on the same MRI scanner with the same 3D T1 protocol at baseline and at 10 years. At 10-year follow-up, they were divided into those with confirmed disability progression (CDP) (85) or without (67) CDP, by standard treatment trial criteria. An optimized, longitudinal source-based morphometry (SBM) pipeline was implemented via a combination of VBM and independent component analysis (ICA) techniques. SBM was used to identify patterns of spatially distinct regions of GM atrophy with common covariation over 10 years in the entire cohort of patients. Next, differences in the loading factors obtained using ICA were compared between patients with CDP and without, while controlling for age and sex. Significance was set at p < 0.05.
Results: 20 components were estimated using ICA. The patterns are similar to those observed using resting state functional MRI, particularly as regards to the default mode and salience networks. Most relevant patterns included: 1) bilateral deep GM (including thalamus caudate, globus pallidus and putamen) and frontal cortex; 2) cerebellum; 3) bilateral thalamus, bilateral caudate and bilateral insular cortex; 4) cingulate cortex. Patients with CDP demonstrated greater atrophy in 2 of the identified patterns (Pattern 1: bilateral thalamus, bilateral precuneous and bilateral sensorimotor (p=.007); Pattern 2: bilateral hippocampi, bilateral temporal, bilateral frontal, bilateral anterior cingulate (p=.024)).
Conclusions: To the best of our knowledge, this is the first longitudinal study in MS showing that the development of GM atrophy progresses in a coherent manner between anatomically and functionally related areas. Longitudinal SBM offers a novel method to better characterize the spatial relationship of GM atrophy and disability than is possible using traditional methods.
Disclosure:
Study Disclosures:
The study is an investigator-initiated study that was supported by Czech Ministries of Education and Health [NT13237-4/2012, PRVOUK-P26/LF1/4, RVO-VFN64165/2012]. The MRI acquisition part of the study was supported by Gedeon Richter and Biogen Idec. The MRI analysis part was supported in part by Biogen Idec.
Financial Relationships/Potential Conflicts of Interest:
Dr. Bergsland has nothing to disclose.
Dr. Horakova received compensation for travel, speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck Serono, Bayer Shering, and Teva, as well as support for research activities from Biogen Idec.
Dr. Dwyer has received personal compensation from Claret Medical and EMD Serono, and research grant support from Novartis.
Dr. Uher received financial support for conference travel and honoraria from Biogen Idec, Novartis, Merck Serono and Genzyme.
Dr. Tyblova received compensation for travel and honoraria from Biogen Idec, Sanofi Aventis, Teva and Merck Serono.
Drs. Seidl, Vaneckova, and Krasensky received financial support for research activities from Biogen Idec.
Dr. Havrdova received speaker honoraria and consultant fees from Actelion, Biogen Idec, Merck Serono, Novartis, Receptos, Sanofi Genzyme, and Merck Serono
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.