Contributions
Abstract: 138
Type: Free Communications
Abstract Category: Clinical aspects of MS - Diagnosis and differential diagnosis
Background: The central vein sign (CVS) has been proposed as a imaging biomarker to differentiate multiple sclerosis (MS) from non-MS patients at advanced MRI. The diagnostic value of the CVS in clinical routine MRI at 3T, however, remains unknown.
Objective: To evaluate the sensitivity and specificity of various CVS-based criteria in differentiating MS from non-MS on clinical 3T MRI in a multi-center study.
Methods: 606 subjects with clinically isolated syndromes suggestive of MS (CIS, n=117), relapsing-remitting MS (RRMS, n=236; 108 with disease duration < 5 years), aquaporine-4 antibody positive NMOSD (n=32), systemic lupus erythematosus (n=25), migraine (n=29), cluster headache (n=5), diabetes mellitus (n=20), or other types of cerebral small vessel disease (n=142) were analysed.
The CVS was examined on parcellated 3T T2*weighted (T2*w) or susceptibility weighted imaging (SWI). The brain parcellation enabled blinding of the raters by avoiding inference on disease type based on the lesion distribution pattern. Sensitivity and specificity values were calculated for different MR sequences and various CVS-based criteria.
Results: 4447 lesions were analysed. The median proportion of a positive CVS was 50% (75% percentile: 67%, range 0-100%) in CIS/RRMS, and 0% (75% percentile: 25%, range 0-100%) in non-MS. A 35% threshold was the best CVS-proportion-based cut-off with a specificity and sensitivity of 82.9%, and 68.1% respectively. In addition, a two-CVS-positive-lesion threshold had a specificity and sensitivity in differentiating between RRMS/CIS and non-MS of 79.3%, and 76.2%, respectively. The specificity and sensitivity of a three-CVS-positive-lesions threshold was 89.0%, and 61.9%, respectively.
We observed comparable findings across all studied disease subgroups, and in patients with CIS or early RRMS as well.
The sensitivity was higher when applying an optimized T2*w sequence (35%-CVS-proportion threshold on T2*w: sensitivity 100%, specificity 86.7%). SWI data still yielded a sufficient differentiation between disease groups (35%-CVS-proportion threshold: sensitivity 66.6%, specificity 82.6%).
Conclusion: The CVS as evaluated on clinical 3T MRI has a high specificity in differentiating MS from non-MS and may thus be used to support the diagnosis of MS. The sensitivity is moderate on SWI and increases when using optimized T2*w imaging. A 35%-proportion-based and a three-positive-CVS-lesions threshold best differentiated between MS and non-MS.
Disclosure: Tim Sinnecker has received travel support from Actelion and Roche, and speaker fees from Biogen. He is employee of the Medical Image Analysis Center AG in Basel. Margareta Clarke has nothing to disclose. Dominik Meier is employee of the Medical Image Analysis Center AG in Basel. Alain Pitiot, Lukas Pirpamer, Massimiliano Calabrese, Nicola De Stefano, and Antonio Giorgio have nothing to disclose related to this work. Menno M. Schoonheim serves on the editorial board of Frontiers of Neurology, receives research support from the Dutch MS Research Foundation, and has received compensation for consulting services or speaker honoraria from ExceMed, Genzyme and Biogen. Friedemann Paul serves on the scientific advisory board for Novartis; received speaker honoraria and travel funding from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Merck Serono, Alexion, Chugai, MedImmune, and Shire; is an academic editor for PLoS ONE; is an associate editor for Neurology® Neuroimmunology & Neuroinflammation; consulted for SanofiGenzyme, Biogen Idec, MedImmune, Shire, and Alexion; and received research support from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Alexion, Merck Serono, German Research Council, Werth Stiftung of the City of Cologne, German Ministry of Education and Research, Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, Arthur Arnstein Foundation Berlin, Guthy Jackson Charitable Foundation, and National Multiple Sclerosis of the USA. Mikolaj Pawlak has nothing to disclose. Ludwig Kappos 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. Àlex 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. Nikos Evangelou has nothing to disclose related to this work. Jens Wuerfel is CEO of MIAC AG Basel, Switzerland. He served on scientific advisory boards of Actelion, Biogen, Genzyme-Sanofi, Novartis, and Roche. He is or was supported by grants of the EU (Horizon2020), German Federal Ministeries of Education and Research (BMBF) and of Economic Affairs and Energy (BMWI).
Abstract: 138
Type: Free Communications
Abstract Category: Clinical aspects of MS - Diagnosis and differential diagnosis
Background: The central vein sign (CVS) has been proposed as a imaging biomarker to differentiate multiple sclerosis (MS) from non-MS patients at advanced MRI. The diagnostic value of the CVS in clinical routine MRI at 3T, however, remains unknown.
Objective: To evaluate the sensitivity and specificity of various CVS-based criteria in differentiating MS from non-MS on clinical 3T MRI in a multi-center study.
Methods: 606 subjects with clinically isolated syndromes suggestive of MS (CIS, n=117), relapsing-remitting MS (RRMS, n=236; 108 with disease duration < 5 years), aquaporine-4 antibody positive NMOSD (n=32), systemic lupus erythematosus (n=25), migraine (n=29), cluster headache (n=5), diabetes mellitus (n=20), or other types of cerebral small vessel disease (n=142) were analysed.
The CVS was examined on parcellated 3T T2*weighted (T2*w) or susceptibility weighted imaging (SWI). The brain parcellation enabled blinding of the raters by avoiding inference on disease type based on the lesion distribution pattern. Sensitivity and specificity values were calculated for different MR sequences and various CVS-based criteria.
Results: 4447 lesions were analysed. The median proportion of a positive CVS was 50% (75% percentile: 67%, range 0-100%) in CIS/RRMS, and 0% (75% percentile: 25%, range 0-100%) in non-MS. A 35% threshold was the best CVS-proportion-based cut-off with a specificity and sensitivity of 82.9%, and 68.1% respectively. In addition, a two-CVS-positive-lesion threshold had a specificity and sensitivity in differentiating between RRMS/CIS and non-MS of 79.3%, and 76.2%, respectively. The specificity and sensitivity of a three-CVS-positive-lesions threshold was 89.0%, and 61.9%, respectively.
We observed comparable findings across all studied disease subgroups, and in patients with CIS or early RRMS as well.
The sensitivity was higher when applying an optimized T2*w sequence (35%-CVS-proportion threshold on T2*w: sensitivity 100%, specificity 86.7%). SWI data still yielded a sufficient differentiation between disease groups (35%-CVS-proportion threshold: sensitivity 66.6%, specificity 82.6%).
Conclusion: The CVS as evaluated on clinical 3T MRI has a high specificity in differentiating MS from non-MS and may thus be used to support the diagnosis of MS. The sensitivity is moderate on SWI and increases when using optimized T2*w imaging. A 35%-proportion-based and a three-positive-CVS-lesions threshold best differentiated between MS and non-MS.
Disclosure: Tim Sinnecker has received travel support from Actelion and Roche, and speaker fees from Biogen. He is employee of the Medical Image Analysis Center AG in Basel. Margareta Clarke has nothing to disclose. Dominik Meier is employee of the Medical Image Analysis Center AG in Basel. Alain Pitiot, Lukas Pirpamer, Massimiliano Calabrese, Nicola De Stefano, and Antonio Giorgio have nothing to disclose related to this work. Menno M. Schoonheim serves on the editorial board of Frontiers of Neurology, receives research support from the Dutch MS Research Foundation, and has received compensation for consulting services or speaker honoraria from ExceMed, Genzyme and Biogen. Friedemann Paul serves on the scientific advisory board for Novartis; received speaker honoraria and travel funding from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Merck Serono, Alexion, Chugai, MedImmune, and Shire; is an academic editor for PLoS ONE; is an associate editor for Neurology® Neuroimmunology & Neuroinflammation; consulted for SanofiGenzyme, Biogen Idec, MedImmune, Shire, and Alexion; and received research support from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Alexion, Merck Serono, German Research Council, Werth Stiftung of the City of Cologne, German Ministry of Education and Research, Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, Arthur Arnstein Foundation Berlin, Guthy Jackson Charitable Foundation, and National Multiple Sclerosis of the USA. Mikolaj Pawlak has nothing to disclose. Ludwig Kappos 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. Àlex 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. Nikos Evangelou has nothing to disclose related to this work. Jens Wuerfel is CEO of MIAC AG Basel, Switzerland. He served on scientific advisory boards of Actelion, Biogen, Genzyme-Sanofi, Novartis, and Roche. He is or was supported by grants of the EU (Horizon2020), German Federal Ministeries of Education and Research (BMBF) and of Economic Affairs and Energy (BMWI).