Contributions
Abstract: 24
Type: Young Scientific Investigators' Session
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: MRI brain T1 gray/white matter (GM/WM) contrast has been recently proposed as a marker for neurodegeneration in Alzheimer's disease. The diagnostic value of this contrast in multiple sclerosis (MS) has yet to be established.
Objective: To compare the T1 GM/WM contrast in patients with MS, migraine and healthy controls (HCs) and investigate the associations with disability outcomes in MS.
Methods: We analyzed pre-contrast 3D MPRAGE data from two independent cohorts. Cohort A (1.5 Tesla): 124 MS patients (65% relapsing-remitting (RR)MS; 66% female, mean disease duration 13±9 years, median EDSS 2.5) and 20 HCs. Cohort B (3 Tesla): 43 RRMS patients (56% female; mean disease duration 3±2 years, median EDSS 1.5), 19 migraine patients (47% with aura and 54% with WM abnormalities on T2 weighted scans) and 37 HCs. WM lesions were segmented manually on T1 and T2 weighted images. GM and WM were segmented using Statistical Parametric Mapping 12. GM and WM fractions were calculated. GM and WM masks were thresholded by 95%. T1 GM/WM contrast ratio was calculated as [mean T1 intensity WM minus mean T1 intensity GM] divided by [mean T1 intensity WM + mean T1 intensity GM]. Clinical outcomes included the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) scores. Associations between variables were investigated using uni- and multivariate general linear models. Results were bootstrapped (case resampling rate: 1000). Reported p-values are age-adjusted.
Results: Mean T1 GM/WM contrast ratio was lower in MS than HCs in both cohorts (p< 0.001). Moreover, T1 GM/WM contrast ratio was lower in MS than migraine (p< 0.001) whereas there was no difference between migraine and HCs. Mean T1 GM/WM contrast was lowest in progressive MS followed by RRMS/clinically isolated syndrome and HCs (11.7±0.7%, 12.2±0.6%, 12.8±0.6; all p< 0.01). In MS, T1 GM/WM contrast was associated with WM lesion volume, disease duration, EDSS and MSFC (all p< 0.05). A multivariable analysis with T1 GM/WM contrast as dependent variable and age, disease duration, T1 and T2 WM lesion volume, GM and WM fraction as independent variables, revealed that GM fraction (p=0.018) and T2 lesion volume (p=0.014) were independently associated with T1 GM/WM contrast ratio.
Conclusions: T1 MPRAGE GM/WM contrast ratio appears sensitive to MS but not to migraine pathology. Further studies should assess the diagnostic and possibly prognostic value of this MRI marker.
Disclosure:
- Tina Mitrovic has nothing to dislose.
- Tim Sinnecker has nothing to dislose.
- Michael Amann has nothing to dislose.
- Pasquale Calabrese has nothing to dislose.
- Yvonne Naegelin has nothing to dislose.
- Tobias Derfuss received speaker fees, research support, travel support, and/or served on Advisory Boards or Steering Committees of Novartis Pharma, Merck, Biogen, Teva, Bayer-Schering, GeNeuro, Mitsubishi Pharma, MedDay, Roche, and Genzyme; he received research support from Biogen, Novartis, Swiss National Research Foundation, University of Basel, and Swiss MS Society.
- Bernhard Décard received travel support and / or fees for the institution (University Hospital Basel) from advisory boards or speaker fees from Allmirall, Biogen, Genzyme, Roche, Teva and Novartis, that were used exclusively for research support.
- Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.
- Laura Gaetano was a temporary employee from Novartis.
- Jens Wuerfel is CEO of the Medical Image Analysis Center Basel.
- Ludwig Kappos´s institution (University Hospital Basel) received and used exclusively for research support: steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Celgene/Receptos, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi, Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva; grants from Bayer HealthCare, Biogen, F. Hoffmann-La Roche Ltd, Merck, Novartis, the European Union, the Roche Research Foundations, the Swiss Multiple Sclerosis Society, the Swiss National Research Foundation.
- Cristina Granziera has nothing to dislose.
- Özgür Yaldizli´s institution University Hospital Basel received grants from ECTRIMS/MAGNIMS, University of Basel, Pro Patient Stiftung University Hospital Basel, Free Academy Basel, Swiss Multiple Sclerosis Society and advisory board fees from Sanofi Genzyme and Novartis Poland exclusively used for support of research and educational activities.
Abstract: 24
Type: Young Scientific Investigators' Session
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: MRI brain T1 gray/white matter (GM/WM) contrast has been recently proposed as a marker for neurodegeneration in Alzheimer's disease. The diagnostic value of this contrast in multiple sclerosis (MS) has yet to be established.
Objective: To compare the T1 GM/WM contrast in patients with MS, migraine and healthy controls (HCs) and investigate the associations with disability outcomes in MS.
Methods: We analyzed pre-contrast 3D MPRAGE data from two independent cohorts. Cohort A (1.5 Tesla): 124 MS patients (65% relapsing-remitting (RR)MS; 66% female, mean disease duration 13±9 years, median EDSS 2.5) and 20 HCs. Cohort B (3 Tesla): 43 RRMS patients (56% female; mean disease duration 3±2 years, median EDSS 1.5), 19 migraine patients (47% with aura and 54% with WM abnormalities on T2 weighted scans) and 37 HCs. WM lesions were segmented manually on T1 and T2 weighted images. GM and WM were segmented using Statistical Parametric Mapping 12. GM and WM fractions were calculated. GM and WM masks were thresholded by 95%. T1 GM/WM contrast ratio was calculated as [mean T1 intensity WM minus mean T1 intensity GM] divided by [mean T1 intensity WM + mean T1 intensity GM]. Clinical outcomes included the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) scores. Associations between variables were investigated using uni- and multivariate general linear models. Results were bootstrapped (case resampling rate: 1000). Reported p-values are age-adjusted.
Results: Mean T1 GM/WM contrast ratio was lower in MS than HCs in both cohorts (p< 0.001). Moreover, T1 GM/WM contrast ratio was lower in MS than migraine (p< 0.001) whereas there was no difference between migraine and HCs. Mean T1 GM/WM contrast was lowest in progressive MS followed by RRMS/clinically isolated syndrome and HCs (11.7±0.7%, 12.2±0.6%, 12.8±0.6; all p< 0.01). In MS, T1 GM/WM contrast was associated with WM lesion volume, disease duration, EDSS and MSFC (all p< 0.05). A multivariable analysis with T1 GM/WM contrast as dependent variable and age, disease duration, T1 and T2 WM lesion volume, GM and WM fraction as independent variables, revealed that GM fraction (p=0.018) and T2 lesion volume (p=0.014) were independently associated with T1 GM/WM contrast ratio.
Conclusions: T1 MPRAGE GM/WM contrast ratio appears sensitive to MS but not to migraine pathology. Further studies should assess the diagnostic and possibly prognostic value of this MRI marker.
Disclosure:
- Tina Mitrovic has nothing to dislose.
- Tim Sinnecker has nothing to dislose.
- Michael Amann has nothing to dislose.
- Pasquale Calabrese has nothing to dislose.
- Yvonne Naegelin has nothing to dislose.
- Tobias Derfuss received speaker fees, research support, travel support, and/or served on Advisory Boards or Steering Committees of Novartis Pharma, Merck, Biogen, Teva, Bayer-Schering, GeNeuro, Mitsubishi Pharma, MedDay, Roche, and Genzyme; he received research support from Biogen, Novartis, Swiss National Research Foundation, University of Basel, and Swiss MS Society.
- Bernhard Décard received travel support and / or fees for the institution (University Hospital Basel) from advisory boards or speaker fees from Allmirall, Biogen, Genzyme, Roche, Teva and Novartis, that were used exclusively for research support.
- Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.
- Laura Gaetano was a temporary employee from Novartis.
- Jens Wuerfel is CEO of the Medical Image Analysis Center Basel.
- Ludwig Kappos´s institution (University Hospital Basel) received and used exclusively for research support: steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Celgene/Receptos, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi, Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva; grants from Bayer HealthCare, Biogen, F. Hoffmann-La Roche Ltd, Merck, Novartis, the European Union, the Roche Research Foundations, the Swiss Multiple Sclerosis Society, the Swiss National Research Foundation.
- Cristina Granziera has nothing to dislose.
- Özgür Yaldizli´s institution University Hospital Basel received grants from ECTRIMS/MAGNIMS, University of Basel, Pro Patient Stiftung University Hospital Basel, Free Academy Basel, Swiss Multiple Sclerosis Society and advisory board fees from Sanofi Genzyme and Novartis Poland exclusively used for support of research and educational activities.