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Research ArticleUltra-High-Field MRI/Imaging of Epilepsy/Demyelinating Diseases/Inflammation/Infection

Multicenter Automated Central Vein Sign Detection Performs as Well as Manual Assessment for the Diagnosis of Multiple Sclerosis

A.R. Manning, V. Letchuman, M.L. Martin, E. Gombos, T. Robert-Fitzgerald, Q. Cao, P. Raza, C.M. O’Donnell, B. Renner, L. Daboul, P. Rodrigues, M. Ramos, J. Derbyshire, C. Azevedo, A. Bar-Or, E. Caverzasi, P.A. Calabresi, B.A.C. Cree, L. Freeman, R.G. Henry, E.E. Longbrake, J. Oh, N. Papinutto, D. Pelletier, R.D. Samudralwar, S. Suthiphosuwan, M.K. Schindler, M. Bilello, J.W. Song, E.S. Sotirchos, N.L. Sicotte, O. Al-Louzi, A.J. Solomon, D.S. Reich, D. Ontaneda, P. Sati, R.T. Shinohara and the NAIMS Cooperative
American Journal of Neuroradiology March 2025, 46 (3) 620-626; DOI: https://doi.org/10.3174/ajnr.A8510
A.R. Manning
aFrom the Penn Statistics in Imaging and Visualization Center (A.R.M., M.L.M., T.R.-F., Q.C., C.M.O., R.T.S.), Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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  • ORCID record for A.R. Manning
V. Letchuman
bTranslational Neuroradiology Section (V.L., L.D., O.A.-L., D.S.R., P.S.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
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M.L. Martin
aFrom the Penn Statistics in Imaging and Visualization Center (A.R.M., M.L.M., T.R.-F., Q.C., C.M.O., R.T.S.), Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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  • ORCID record for M.L. Martin
E. Gombos
cDepartment of Neurology (E.G., B.R., N.L.S., O.A.-L., P.S.), Cedars-Sinai Medical Center, Los Angeles, California
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T. Robert-Fitzgerald
aFrom the Penn Statistics in Imaging and Visualization Center (A.R.M., M.L.M., T.R.-F., Q.C., C.M.O., R.T.S.), Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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Q. Cao
aFrom the Penn Statistics in Imaging and Visualization Center (A.R.M., M.L.M., T.R.-F., Q.C., C.M.O., R.T.S.), Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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P. Raza
dCleveland Clinic Lerner College of Medicine (P. Raza, L.D.), Cleveland, Ohio
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  • ORCID record for P. Raza
C.M. O’Donnell
aFrom the Penn Statistics in Imaging and Visualization Center (A.R.M., M.L.M., T.R.-F., Q.C., C.M.O., R.T.S.), Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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  • ORCID record for C.M. O’Donnell
B. Renner
cDepartment of Neurology (E.G., B.R., N.L.S., O.A.-L., P.S.), Cedars-Sinai Medical Center, Los Angeles, California
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L. Daboul
bTranslational Neuroradiology Section (V.L., L.D., O.A.-L., D.S.R., P.S.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
dCleveland Clinic Lerner College of Medicine (P. Raza, L.D.), Cleveland, Ohio
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  • ORCID record for L. Daboul
P. Rodrigues
eQMENTA Inc. (P. Rodrigues, M.R.), Boston, Massachusetts
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M. Ramos
eQMENTA Inc. (P. Rodrigues, M.R.), Boston, Massachusetts
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J. Derbyshire
fSection on Functional Imaging Methods (J.D.), Laboratory of Brain and Cognition, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
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C. Azevedo
gDepartment of Neurology (C.A., D.P.), University of Southern California, Los Angeles, California
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A. Bar-Or
hDepartment of Neurology (A.B.-O., R.D.S., M.K.S.), University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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E. Caverzasi
i UCSF Weill Institute for Neurosciences (E.C., B.A.C.C., R.G.H., N.P.), Department of Neurology, University of California San Francisco, San Francisco, California
jDepartment of Brain and Behavioral Sciences (E.C.), University of Pavia, Pavia, Italy; Neuroradiology Department, Advanced Imaging and Radiomics Center (E.C.), IRCCS Mondino Foundation, Pavia, Italy
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P.A. Calabresi
kDepartment of Neurology (P.A.C., E.S.S.), Johns Hopkins University, Baltimore, Maryland
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  • ORCID record for P.A. Calabresi
B.A.C. Cree
i UCSF Weill Institute for Neurosciences (E.C., B.A.C.C., R.G.H., N.P.), Department of Neurology, University of California San Francisco, San Francisco, California
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L. Freeman
lDepartment of Neurology, Dell Medical School (L.F.), The University of Texas at Austin, Austin, Texas
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R.G. Henry
i UCSF Weill Institute for Neurosciences (E.C., B.A.C.C., R.G.H., N.P.), Department of Neurology, University of California San Francisco, San Francisco, California
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E.E. Longbrake
mDepartment of Neurology (E.E.L.), Yale University, New Haven, Connecticut
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J. Oh
nDivision of Neurology (J.O.), Department of Medicine, St. Michael’s Hospital, University of Toronto, Toronto, Canada
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N. Papinutto
i UCSF Weill Institute for Neurosciences (E.C., B.A.C.C., R.G.H., N.P.), Department of Neurology, University of California San Francisco, San Francisco, California
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D. Pelletier
gDepartment of Neurology (C.A., D.P.), University of Southern California, Los Angeles, California
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R.D. Samudralwar
hDepartment of Neurology (A.B.-O., R.D.S., M.K.S.), University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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S. Suthiphosuwan
oDepartment of Medical Imaging (S.S.), St. Michael’s Hospital, University of Toronto, Toronto, Canada
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M.K. Schindler
hDepartment of Neurology (A.B.-O., R.D.S., M.K.S.), University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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M. Bilello
pDepartment of Radiology (M.B., J.W.S.), University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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J.W. Song
pDepartment of Radiology (M.B., J.W.S.), University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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E.S. Sotirchos
kDepartment of Neurology (P.A.C., E.S.S.), Johns Hopkins University, Baltimore, Maryland
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N.L. Sicotte
cDepartment of Neurology (E.G., B.R., N.L.S., O.A.-L., P.S.), Cedars-Sinai Medical Center, Los Angeles, California
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O. Al-Louzi
bTranslational Neuroradiology Section (V.L., L.D., O.A.-L., D.S.R., P.S.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
cDepartment of Neurology (E.G., B.R., N.L.S., O.A.-L., P.S.), Cedars-Sinai Medical Center, Los Angeles, California
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A.J. Solomon
qDepartment of Neurological Sciences (A.J.S.), Larner College of Medicine at the University of Vermont, Burlington, Vermont
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D.S. Reich
bTranslational Neuroradiology Section (V.L., L.D., O.A.-L., D.S.R., P.S.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
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D. Ontaneda
rMellen Center for Multiple Sclerosis (D.O.), Cleveland Clinic, Cleveland, Ohio
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P. Sati
bTranslational Neuroradiology Section (V.L., L.D., O.A.-L., D.S.R., P.S.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
cDepartment of Neurology (E.G., B.R., N.L.S., O.A.-L., P.S.), Cedars-Sinai Medical Center, Los Angeles, California
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R.T. Shinohara
aFrom the Penn Statistics in Imaging and Visualization Center (A.R.M., M.L.M., T.R.-F., Q.C., C.M.O., R.T.S.), Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
sCenter for Biomedical Image Computing and Analytics (R.T.S.), University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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Abstract

BACKGROUND AND PURPOSE: The central vein sign (CVS) is a proposed diagnostic imaging biomarker for multiple sclerosis (MS). The proportion of white matter lesions exhibiting the CVS (CVS+) is higher in patients with MS compared with its radiologic mimics. Evaluation for CVS+ lesions in prior studies has been performed by manual rating, an approach that is time-consuming and has variable interrater reliability. Accurate automated methods would facilitate efficient assessment for CVS. The objective of this study was to compare the performance of an automated CVS detection method with manual rating for the diagnosis of MS.

MATERIALS AND METHODS: 3T MRI was acquired in 86 participants undergoing evaluation for MS in a 9-site multicenter study. Participants presented with either typical or atypical clinical syndromes for MS. An automated CVS detection method was employed and compared with manual rating, including total CVS+ proportion and a simplified counting method in which experts visually identified up to 6 CVS+ lesions by using FLAIR* contrast (a voxelwise product of T2 FLAIR and postcontrast T2*-EPI).

RESULTS: Automated CVS processing was completed in 79 of 86 participants (91%), of whom 28 (35%) fulfilled the 2017 McDonald criteria at the time of imaging. The area under the receiver operating characteristic curve (AUC) for discrimination between participants with and without MS for the automated CVS approach was 0.78 (95% CI: [0.67,0.88]). This was not significantly different from simplified manual counting methods (select6*) (0.80 [0.69,0.91]) or manual assessment of total CVS+ proportion (0.89 [0.82,0.96]). In a sensitivity analysis excluding 11 participants whose MRI exhibited motion artifact, the AUC for the automated method was 0.81 [0.70,0.91], which was not statistically different from that for select6* (0.79 [0.68,0.92]) or manual assessment of total CVS+ proportion (0.89 [0.81,0.97]).

CONCLUSIONS: Automated CVS assessment was comparable to manual CVS scoring for differentiating patients with MS from those with other diagnoses. Large, prospective, multicenter studies utilizing automated methods and enrolling the breadth of disorders referred for suspicion of MS are needed to determine optimal approaches for clinical implementation of an automated CVS detection method.

ABBREVIATIONS:

AUC
area under the curve
CVS
central vein sign
EDSS
Expanded Disability Status Score
GBCA
gadolinium-based contrast agent
IRR
interrater reliability
MIMoSA
Method for InterModal Segmentation Analysis
NAIMS
North American Imaging in MS Cooperative
ROC
receiver operating characteristic
SD
standard deviation
WML
white matter lesion
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Cite this article
A.R. Manning, V. Letchuman, M.L. Martin, E. Gombos, T. Robert-Fitzgerald, Q. Cao, P. Raza, C.M. O’Donnell, B. Renner, L. Daboul, P. Rodrigues, M. Ramos, J. Derbyshire, C. Azevedo, A. Bar-Or, E. Caverzasi, P.A. Calabresi, B.A.C. Cree, L. Freeman, R.G. Henry, E.E. Longbrake, J. Oh, N. Papinutto, D. Pelletier, R.D. Samudralwar, S. Suthiphosuwan, M.K. Schindler, M. Bilello, J.W. Song, E.S. Sotirchos, N.L. Sicotte, O. Al-Louzi, A.J. Solomon, D.S. Reich, D. Ontaneda, P. Sati, R.T. Shinohara, the NAIMS Cooperative
Multicenter Automated Central Vein Sign Detection Performs as Well as Manual Assessment for the Diagnosis of Multiple Sclerosis
American Journal of Neuroradiology Mar 2025, 46 (3) 620-626; DOI: 10.3174/ajnr.A8510

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Automated vs Manual Central Vein Sign in MS
A.R. Manning, V. Letchuman, M.L. Martin, E. Gombos, T. Robert-Fitzgerald, Q. Cao, P. Raza, C.M. O’Donnell, B. Renner, L. Daboul, P. Rodrigues, M. Ramos, J. Derbyshire, C. Azevedo, A. Bar-Or, E. Caverzasi, P.A. Calabresi, B.A.C. Cree, L. Freeman, R.G. Henry, E.E. Longbrake, J. Oh, N. Papinutto, D. Pelletier, R.D. Samudralwar, S. Suthiphosuwan, M.K. Schindler, M. Bilello, J.W. Song, E.S. Sotirchos, N.L. Sicotte, O. Al-Louzi, A.J. Solomon, D.S. Reich, D. Ontaneda, P. Sati, R.T. Shinohara, the NAIMS Cooperative
American Journal of Neuroradiology Mar 2025, 46 (3) 620-626; DOI: 10.3174/ajnr.A8510
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