@article{af09db4643354c7483bce46373ce469d,
title = "Lesion size and shape in central vein sign assessment for multiple sclerosis diagnosis: An in vivo and postmortem MRI study",
abstract = "Background: The “central vein sign” (CVS), a linear hypointensity on T2*-weighted imaging corresponding to a central vein/venule, is associated with multiple sclerosis (MS) lesions. The effect of lesion-size exclusion criteria on MS diagnostic accuracy has not been extensively studied. Objective: Investigate the optimal lesion-size exclusion criteria for CVS use in MS diagnosis. Methods: Cross-sectional study of 163 MS and 51 non-MS, and radiological/histopathological correlation of 5 MS and 1 control autopsy cases. The effects of lesion-size exclusion on MS diagnosis using the CVS, and intralesional vein detection on histopathology were evaluated. Results: CVS+ lesions were larger compared to CVS− lesions, with effect modification by MS diagnosis (mean difference +7.7 mm3, p = 0.004). CVS percentage-based criteria with no lesion-size exclusion showed the highest diagnostic accuracy in differentiating MS cases. However, a simple count of three or more CVS+ lesions greater than 3.5 mm is highly accurate and can be rapidly implemented (sensitivity 93%; specificity 88%). On magnetic resonance imaging (MRI)-histopathological correlation, the CVS had high specificity for identifying intralesional veins (0/7 false positives). Conclusion: Lesion-size measures add important information when using CVS+ lesion counts for MS diagnosis. The CVS is a specific biomarker corresponding to intralesional veins on histopathology.",
keywords = "Biomarkers, T2 lesions, central vein sign, magnetic resonance imaging, multiple sclerosis, post mortem",
author = "Omar Al-Louzi and Sargis Manukyan and Maxime Donadieu and Martina Absinta and Vijay Letchuman and Brent Calabresi and Parth Desai and Beck, {Erin S.} and Snehashis Roy and Joan Ohayon and Pham, {Dzung L.} and Anish Thomas and Steven Jacobson and Irene Cortese and Auluck, {Pavan K.} and Govind Nair and Pascal Sati and Reich, {Daniel S.}",
note = "Funding Information: The authors thank all the participants in this study as well as their family members. The authors also acknowledge the contributions of Frances Andrada and Jenifer Dwyer from the National Institute of Neurological Disorders and Stroke (NINDS) Neuroimmunology Clinic to the recruitment, care, and collection of clinical data from the study participants, as well as the NINDS neuroimmunology clinical fellows. The authors also thank Dr John Ostuni and the NINDS information technology department for help with servers and software maintenance, and the staff of the Functional Magnetic Resonance Facility (FMRIF) and radiology department technicians who were instrumental with regards to image acquisition. This study utilized the computational resources of the Biowulf system at the National Institutes of Health, Bethesda, MD, USA (https://hpc.nih.gov/). The authors also wish to thank the Human Brain Collection Core (HBCC) within the National Institute of Mental Health{\textquoteright}s (NIMH) Division of Intramural Research Programs (DIRP) for their assistance with the autopsies and pathological specimen collection, as well as the National Cancer Institute Laboratory of Pathology. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Intramural Research Program of the NINDS/NIH, the Adelson Medical Research Foundation, and the National Multiple Sclerosis Society (NMSS) (SI-2004-36590). O.A.-L. is the recipient of an NMSS-American Brain Foundation Clinician Scientist Development Award (FAN-1807-32163). D.L.P. is supported by an NMSS grant (RG-1907-34570). S.M. is supported by the NIH Undergraduate Scholars Program. V.L. is supported by the Foundation of the Consortium of Multiple Sclerosis Centers and the NIH Medical Research Scholars Program (a public–private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, Genentech, the American Association for Dental Research, and the Colgate-Palmolive Company). E.S.B. is supported by a National Multiple Sclerosis Society Career Transition Fellowship (TA-1805-31038). M.A. is supported by the Conrad N. Hilton Foundation (grant no. 17313), the Cariplo Foundation (grant no. 2019-1677), the FRRB Early Career Award (grant no. 1750327), and by the International Progressive MS Alliance (PA-2107-38081). Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr O.A., S.M., Dr M.D., V.L., B.C., Dr P.D., Dr E.B., Dr S.R., J.O., Dr D.L.P., Dr A.T., Dr S.J., Dr I.C., Dr P.A., Dr G.N., and Dr P.S. have no disclosures pertaining to the work presented. Dr M.A. received speaker and/or consultancy fees from Celgene and Sanofi-Genzyme, unrelated to the current project. Dr D.S.R. received research funding from Abata, Sanofi-Genzyme, and Vertex, unrelated to the current project. Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Intramural Research Program of the NINDS/NIH, the Adelson Medical Research Foundation, and the National Multiple Sclerosis Society (NMSS) (SI-2004-36590). O.A.-L. is the recipient of an NMSS-American Brain Foundation Clinician Scientist Development Award (FAN-1807-32163). D.L.P. is supported by an NMSS grant (RG-1907-34570). S.M. is supported by the NIH Undergraduate Scholars Program. V.L. is supported by the Foundation of the Consortium of Multiple Sclerosis Centers and the NIH Medical Research Scholars Program (a public–private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, Genentech, the American Association for Dental Research, and the Colgate-Palmolive Company). E.S.B. is supported by a National Multiple Sclerosis Society Career Transition Fellowship (TA-1805-31038). M.A. is supported by the Conrad N. Hilton Foundation (grant no. 17313), the Cariplo Foundation (grant no. 2019-1677), the FRRB Early Career Award (grant no. 1750327), and by the International Progressive MS Alliance (PA-2107-38081). Publisher Copyright: {\textcopyright} The Author(s), 2022.",
year = "2022",
month = oct,
doi = "10.1177/13524585221097560",
language = "English (US)",
volume = "28",
pages = "1891--1902",
journal = "Multiple Sclerosis Journal",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",
number = "12",
}