Tim Sinnecker1,2,3,4, Margareta A Clarke5,6, Dominik Meier2,4, Christian Enzinger7, Massimiliano Calabrese8, Nicola De Stefano9, Alain Pitiot10, Antonio Giorgio9, Menno M Schoonheim11, Friedemann Paul3,12, Mikolaj A Pawlak13, Reinhold Schmidt14, Ludwig Kappos1, Xavier Montalban15,16, Àlex Rovira15, Nikos Evangelou17, Jens Wuerfel2,3,4,12. 1. Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital, University of Basel, Basel, Switzerland. 2. Medical Image Analysis Center, Basel, Switzerland. 3. Neurocure Clinical Research Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. 4. qbig, Department of Biomedical Engineering, University of Basel, Basel, Switzerland. 5. School of Psychology, University of Nottingham, Nottingham, United Kingdom. 6. Clinical Neurology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom. 7. Division of Neuroradiology, Vascular and Interventional Radiology, Departments of Neurology and Radiology, Medical University of Graz, Graz, Austria. 8. Neurology Unit, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy. 9. Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy. 10. Laboratory of Image and Data Analysis, Ilixa Ltd, London, United Kingdom. 11. Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. 12. Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health and Max Delbrück Center for Molecular Medicine, Berlin, Germany. 13. Department of Neurology and Cerebrovascular Disorders, Poznan University of Medical Sciences, Poznan, Poland. 14. Department of Neurology, Medical University of Graz, Graz, Austria. 15. Section of Neuroradiology, Department of Radiology (IDI), VHIR, Barcelona, Spain. 16. Division of Neurology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. 17. Division of Clinical Neuroscience, University of Nottingham, Nottingham, United Kingdom.
Abstract
Importance: The central vein sign has been proposed as a specific imaging biomarker for distinguishing between multiple sclerosis (MS) and not MS, mainly based on findings from ultrahigh-field magnetic resonance imaging (MRI) studies. The diagnostic value of the central vein sign in a multicenter setting with a variety of clinical 3 tesla (T) MRI protocols, however, remains unknown. Objective: To evaluate the sensitivity and specificity of various central vein sign lesion criteria for differentiating MS from non-MS conditions using 3T brain MRI with various commonly used pulse sequences. Design, Setting, and Participants: This large multicenter, cross-sectional study enrolled participants (n = 648) of ongoing observational studies and patients included in neuroimaging research databases of 8 neuroimaging centers in Europe. Patient enrollment and MRI data collection were performed between January 1, 2010, and November 30, 2016. Data analysis was conducted between January 1, 2016, and April 30, 2018. Investigators were blinded to participant diagnosis by a novel blinding procedure. Main Outcomes and Measures: Occurrence of central vein sign was detected on 3T T2*-weighted or susceptibility-weighted imaging. Sensitivity and specificity were assessed for these MRI sequences and for different central vein sign lesion criteria, which were defined by the proportion of lesions with central vein sign or by absolute numbers of lesions with central vein sign. Results: A total of 606 participants were included in the study after exclusion of 42 participants. Among the 606 participants, 413 (68.2%) were women. Patients with clinically isolated syndrome and relapsing-remitting MS (RRMS) included 235 women (66.6%) and had a median (range) age of 37 (14.7-61.4) years, a median (range) disease duration of 2 (0-33) years, and a median (range) Expanded Disability Status Scale score of 1.5 (0-6.5). Patients without MS included 178 women (70.4%) and had a median (range) age of 54 (18-83) years. A total of 4447 lesions were analyzed in a total of 487 patients: 690 lesions in 98 participants with clinically isolated syndrome, 2815 lesions in 225 participants with RRMS, 54 lesions in 13 participants with neuromyelitis optica spectrum disorder, 54 lesions in 14 participants with systemic lupus erythematosus, 121 lesions in 29 participants with migraine or cluster headache, 240 lesions in 20 participants with diabetes, and 473 lesions in 88 participants with other types of small-vessel disease. The sensitivity was 68.1% and specificity was 82.9% for distinguishing MS from not MS using a 35% central vein sign proportion threshold. The 3 central vein sign lesion criteria had a sensitivity of 61.9% and specificity of 89.0%. Sensitivity was higher when an optimized T2*-weighted sequence was used. Conclusions and Relevance: In this study, use of the central vein sign at 3T MRI yielded a high specificity and a moderate sensitivity in differentiating MS from not MS; international, multicenter studies may be needed to ascertain whether the central vein sign-based criteria can accurately detect MS.
Importance: The central vein sign has been proposed as a specific imaging biomarker for distinguishing between multiple sclerosis (MS) and not MS, mainly based on findings from ultrahigh-field magnetic resonance imaging (MRI) studies. The diagnostic value of the central vein sign in a multicenter setting with a variety of clinical 3 tesla (T) MRI protocols, however, remains unknown. Objective: To evaluate the sensitivity and specificity of various central vein sign lesion criteria for differentiating MS from non-MS conditions using 3T brain MRI with various commonly used pulse sequences. Design, Setting, and Participants: This large multicenter, cross-sectional study enrolled participants (n = 648) of ongoing observational studies and patients included in neuroimaging research databases of 8 neuroimaging centers in Europe. Patient enrollment and MRI data collection were performed between January 1, 2010, and November 30, 2016. Data analysis was conducted between January 1, 2016, and April 30, 2018. Investigators were blinded to participant diagnosis by a novel blinding procedure. Main Outcomes and Measures: Occurrence of central vein sign was detected on 3T T2*-weighted or susceptibility-weighted imaging. Sensitivity and specificity were assessed for these MRI sequences and for different central vein sign lesion criteria, which were defined by the proportion of lesions with central vein sign or by absolute numbers of lesions with central vein sign. Results: A total of 606 participants were included in the study after exclusion of 42 participants. Among the 606 participants, 413 (68.2%) were women. Patients with clinically isolated syndrome and relapsing-remitting MS (RRMS) included 235 women (66.6%) and had a median (range) age of 37 (14.7-61.4) years, a median (range) disease duration of 2 (0-33) years, and a median (range) Expanded Disability Status Scale score of 1.5 (0-6.5). Patients without MS included 178 women (70.4%) and had a median (range) age of 54 (18-83) years. A total of 4447 lesions were analyzed in a total of 487 patients: 690 lesions in 98 participants with clinically isolated syndrome, 2815 lesions in 225 participants with RRMS, 54 lesions in 13 participants with neuromyelitis optica spectrum disorder, 54 lesions in 14 participants with systemic lupus erythematosus, 121 lesions in 29 participants with migraine or cluster headache, 240 lesions in 20 participants with diabetes, and 473 lesions in 88 participants with other types of small-vessel disease. The sensitivity was 68.1% and specificity was 82.9% for distinguishing MS from not MS using a 35% central vein sign proportion threshold. The 3 central vein sign lesion criteria had a sensitivity of 61.9% and specificity of 89.0%. Sensitivity was higher when an optimized T2*-weighted sequence was used. Conclusions and Relevance: In this study, use of the central vein sign at 3T MRI yielded a high specificity and a moderate sensitivity in differentiating MS from not MS; international, multicenter studies may be needed to ascertain whether the central vein sign-based criteria can accurately detect MS.
Authors: M I Gaitán; P Yañez; M E Paday Formenti; I Calandri; E Figueiredo; P Sati; J Correale Journal: AJNR Am J Neuroradiol Date: 2020-02-13 Impact factor: 3.825
Authors: M A Clarke; D Pareto; L Pessini-Ferreira; G Arrambide; M Alberich; F Crescenzo; S Cappelle; M Tintoré; J Sastre-Garriga; C Auger; X Montalban; N Evangelou; À Rovira Journal: AJNR Am J Neuroradiol Date: 2020-05-21 Impact factor: 3.825
Authors: Pietro Maggi; Mário João Fartaria; João Jorge; Francesco La Rosa; Martina Absinta; Pascal Sati; Reto Meuli; Renaud Du Pasquier; Daniel S Reich; Meritxell Bach Cuadra; Cristina Granziera; Jonas Richiardi; Tobias Kober Journal: NMR Biomed Date: 2020-03-03 Impact factor: 4.478