Contributions
Abstract: 232
Type: Free Communications
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: While techniques for spinal cord (SC) volumetry have improved, a consensus about the optimal choice of vertebrabl level, section length, or suitability of sagittal brain images for cervical cord atrophy quantification in MS is lacking.
Objectives: To quantify the SC cross-sectional area (CSA) using SCT V3.1.0; PropSeg (SCT ), NeuroQlab (NQL) and Jim7 (JIM) in a European multicenter study of 98 MS patients and 52 healthy controls (HC).
Aims: To analyze CSA intra- and inter-scanner reproducibility and the sensitivity for MS-related changes using different measurement settings on sagittal SC and brain MRI.
Methods: 3Tesla MRI included sagittal 3D-T1w imaging of brain and SC. Repeatability (3 scans/ same day in 6 centers) was assessed in one healthy subject. MS patients (relapsing MS [rMS; n=50], progressive MS [pMS, n=25], clinically isolated syndrome [CIS; n=22]) and HC were scanned at baseline and 1 year follow-up (n=87). CSA was quantified on SC and brain images at different SC-levels (C1-2; C2/3; C1-7).
Results: CSA repeatability was best using SC MRI at C1-7, closely followed by brain MRI at C1-2 (max. absolute difference/mm2of repeated scans: SCT: 1.3 vs. 1.4; NQL: 0.6 vs. 1.1, JIM: 0.9 vs. 1.0). Intra-class correlation coefficients (ICC) for consistency between baseline and follow-up in HC were highest for brain MRI at C1-2 (ICC>0.98 for SCT, NQL and JIM). CSA [mm2] was comparable using JIM and NQL, but lower for SCT at all SC-levels (example: mean[SD] at C1-7 in HC vs. MS: SCT: 73.8[8.2] vs. 69.3[11.7] / NQL: 80.8[8.1] vs. 76.1[10.4] / Jim: 77.4[8.0] vs. 73.0[9.9]). For all SC-levels and scan types, each method detected significant CSA differences between MS and HC (t-tests), between the patient subgroups (F-tests), and showed significant correlations (Spearman) with disability. Discrimination between rMS and pMS by ROC analysis was poor to fair for all methods, with best results in NQL (area under curve C1-7: 0.793, brain MRI at C1-2: 0.736). Longitudinal changes of CSA were not significant, with mean differences comparing MS vs. HC: SCT / NQL / JIM, example C1-7 SC-level: 0.3 vs. 1.2 / 0.2 vs. -0.4 / 0.6 vs. -0.8 [mm2]).
Conclusions: Reproducibility and sensitivity to discriminate between MS and HC were high for all three methods. Best performance achieved by C1-7 SC MRI was only slightly superior to CSA assessment using brain MRI. Differences in CSA between methods have to be accounted for when interpreting SC atrophy studies.
Disclosure: Carsten Lukas received a research grant by the German Federal Ministry for Education and Research, BMBF, German Competence Network Multiple Sclerosis (KKNMS), grant no.01GI1601I, has received consulting and speaker´s honoraria from Biogen Idec, Bayer Schering, Daiichi Sanykyo, Merck Serono, Novartis, Sanofi, Genzyme and TEVA.
Ferran Prados received a Guarantors of Brain fellowship.
Paola Valsasina: nothing to disclose
Katrin Parmar holds a grant of the Baasch-Medicus foundation; her institution (University Hospital Basel) received speakers honoraria from Novartis and ExceMED and travel support by Novartis Switzerland.
Iman Brower received financial support by research grants from Novartis, Teva and the Dutch MS Research Foundation.
Barbara Bellenberg received financial support by the German Federal Ministry for Education and Research, BMBF, German Competence Network Multiple Sclerosis (KKNMS), grant no.01GI1601I.
Alex Rovira serves on scientific advisory boards for Novartis, Sanofi-Genzyme, Icometrix, SyntheticMR, and OLEA Medical, and has received speaker honoraria from Bayer, Sanofi-Genzyme, Bracco, Merck-Serono, Teva Pharmaceutical Industries Ltd, Novartis, Roche and Biogen Idec.
Declan Chard has received honoraria (paid to his employer) from Excemed for faculty-led education work; had meeting expenses funded by Merck, MS Trust, National MS Society, Novartis, Société des Neurosciences and Swiss MS Society; and has previously held stock in GlaxoSmithKline; he has received research funding from the International Progressive MS Alliance, the MS Society of Great Britain and Northern Ireland, and the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre.
Ludwig Kappos´ Institution received steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products; the research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
Maria A. Rocca received speakers honoraria from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla.
Massimo Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).
Olga Ciccarelli received research grants from the MS Society of Great Britain & Northern Ireland, Engineering and Physical Sciences Research Council (EPSCR), University College London/University College London Hospitals NHS Foundation Trust (UCL/UCLH), National Institute for Health Research (NIHR) Biomedical Research Centre (BRC), Wellcome Trust, EUH2020, Spinal Cord Research Foundation and Rosetrees Trust; she serves as a consultant for Novartis, Teva & Roche and received an honorarium from the AAN as Associate Editor of Neurology; she serves on the Editorial Board of Multiple Sclerosis Journal.
Frederik Barkhof has received consultance and speaker honoraria from Bayer-Schering Pharma, Biogen-IDEC, TEVA, Merck-Serono, Novartis, Roche, Jansen Research, Genzyme-Sanofi, IXICO Ltd., GeNeuro and Apitope Ltd; he is a honorary board member for the Journals: Brain, Eur. Radiology, Neurology, Multiple Sclerosis Journal, and Radiology; his institution has received grants by AMYPAD (IMI), EuroPOND (H2020), UK MS Society, Dutch MS Society, PICTURE (IMDI-NWO), NIHR UCLH Biomedical Research Centre (BRC), ECTRIMS-MAGNIMS.
Hugo Vrenken has received research grants from Novartis, MerckSerono and Teva, and consulting fees from MerckSerono; all funds were paid directly to his institution.
Abstract: 232
Type: Free Communications
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: While techniques for spinal cord (SC) volumetry have improved, a consensus about the optimal choice of vertebrabl level, section length, or suitability of sagittal brain images for cervical cord atrophy quantification in MS is lacking.
Objectives: To quantify the SC cross-sectional area (CSA) using SCT V3.1.0; PropSeg (SCT ), NeuroQlab (NQL) and Jim7 (JIM) in a European multicenter study of 98 MS patients and 52 healthy controls (HC).
Aims: To analyze CSA intra- and inter-scanner reproducibility and the sensitivity for MS-related changes using different measurement settings on sagittal SC and brain MRI.
Methods: 3Tesla MRI included sagittal 3D-T1w imaging of brain and SC. Repeatability (3 scans/ same day in 6 centers) was assessed in one healthy subject. MS patients (relapsing MS [rMS; n=50], progressive MS [pMS, n=25], clinically isolated syndrome [CIS; n=22]) and HC were scanned at baseline and 1 year follow-up (n=87). CSA was quantified on SC and brain images at different SC-levels (C1-2; C2/3; C1-7).
Results: CSA repeatability was best using SC MRI at C1-7, closely followed by brain MRI at C1-2 (max. absolute difference/mm2of repeated scans: SCT: 1.3 vs. 1.4; NQL: 0.6 vs. 1.1, JIM: 0.9 vs. 1.0). Intra-class correlation coefficients (ICC) for consistency between baseline and follow-up in HC were highest for brain MRI at C1-2 (ICC>0.98 for SCT, NQL and JIM). CSA [mm2] was comparable using JIM and NQL, but lower for SCT at all SC-levels (example: mean[SD] at C1-7 in HC vs. MS: SCT: 73.8[8.2] vs. 69.3[11.7] / NQL: 80.8[8.1] vs. 76.1[10.4] / Jim: 77.4[8.0] vs. 73.0[9.9]). For all SC-levels and scan types, each method detected significant CSA differences between MS and HC (t-tests), between the patient subgroups (F-tests), and showed significant correlations (Spearman) with disability. Discrimination between rMS and pMS by ROC analysis was poor to fair for all methods, with best results in NQL (area under curve C1-7: 0.793, brain MRI at C1-2: 0.736). Longitudinal changes of CSA were not significant, with mean differences comparing MS vs. HC: SCT / NQL / JIM, example C1-7 SC-level: 0.3 vs. 1.2 / 0.2 vs. -0.4 / 0.6 vs. -0.8 [mm2]).
Conclusions: Reproducibility and sensitivity to discriminate between MS and HC were high for all three methods. Best performance achieved by C1-7 SC MRI was only slightly superior to CSA assessment using brain MRI. Differences in CSA between methods have to be accounted for when interpreting SC atrophy studies.
Disclosure: Carsten Lukas received a research grant by the German Federal Ministry for Education and Research, BMBF, German Competence Network Multiple Sclerosis (KKNMS), grant no.01GI1601I, has received consulting and speaker´s honoraria from Biogen Idec, Bayer Schering, Daiichi Sanykyo, Merck Serono, Novartis, Sanofi, Genzyme and TEVA.
Ferran Prados received a Guarantors of Brain fellowship.
Paola Valsasina: nothing to disclose
Katrin Parmar holds a grant of the Baasch-Medicus foundation; her institution (University Hospital Basel) received speakers honoraria from Novartis and ExceMED and travel support by Novartis Switzerland.
Iman Brower received financial support by research grants from Novartis, Teva and the Dutch MS Research Foundation.
Barbara Bellenberg received financial support by the German Federal Ministry for Education and Research, BMBF, German Competence Network Multiple Sclerosis (KKNMS), grant no.01GI1601I.
Alex Rovira serves on scientific advisory boards for Novartis, Sanofi-Genzyme, Icometrix, SyntheticMR, and OLEA Medical, and has received speaker honoraria from Bayer, Sanofi-Genzyme, Bracco, Merck-Serono, Teva Pharmaceutical Industries Ltd, Novartis, Roche and Biogen Idec.
Declan Chard has received honoraria (paid to his employer) from Excemed for faculty-led education work; had meeting expenses funded by Merck, MS Trust, National MS Society, Novartis, Société des Neurosciences and Swiss MS Society; and has previously held stock in GlaxoSmithKline; he has received research funding from the International Progressive MS Alliance, the MS Society of Great Britain and Northern Ireland, and the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre.
Ludwig Kappos´ Institution received steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products; the research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
Maria A. Rocca received speakers honoraria from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla.
Massimo Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).
Olga Ciccarelli received research grants from the MS Society of Great Britain & Northern Ireland, Engineering and Physical Sciences Research Council (EPSCR), University College London/University College London Hospitals NHS Foundation Trust (UCL/UCLH), National Institute for Health Research (NIHR) Biomedical Research Centre (BRC), Wellcome Trust, EUH2020, Spinal Cord Research Foundation and Rosetrees Trust; she serves as a consultant for Novartis, Teva & Roche and received an honorarium from the AAN as Associate Editor of Neurology; she serves on the Editorial Board of Multiple Sclerosis Journal.
Frederik Barkhof has received consultance and speaker honoraria from Bayer-Schering Pharma, Biogen-IDEC, TEVA, Merck-Serono, Novartis, Roche, Jansen Research, Genzyme-Sanofi, IXICO Ltd., GeNeuro and Apitope Ltd; he is a honorary board member for the Journals: Brain, Eur. Radiology, Neurology, Multiple Sclerosis Journal, and Radiology; his institution has received grants by AMYPAD (IMI), EuroPOND (H2020), UK MS Society, Dutch MS Society, PICTURE (IMDI-NWO), NIHR UCLH Biomedical Research Centre (BRC), ECTRIMS-MAGNIMS.
Hugo Vrenken has received research grants from Novartis, MerckSerono and Teva, and consulting fees from MerckSerono; all funds were paid directly to his institution.