Imaging Mechanisms of Disease Progression in Multiple Sclerosis: Beyond Brain Atrophy
Corresponding Author
Francesca Bagnato
Neuroimaging Unit, Neuroimmunology Division, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN
These individuals were workshop organizers and are equal contributors to this work.
Correspondence: Address correspondence to Francesca Bagnato, Neuroimaging Unit, Neuroimmunology Division, Department of Neurology, Vanderbilt University Medical Center, 2201 Children's Way, Suite 1222, Nashville, TN 37212. E-mail: [email protected].
Search for more papers by this authorSusan A. Gauthier
Judith Jaffe Multiple Sclerosis Center, Department of Neurology, Feil Family Brain and Mind Institute, and Department of Radiology, Weill Cornell Medicine, New York, NY
These individuals were workshop organizers and are equal contributors to this work.
Search for more papers by this authorCornelia Laule
Department of Radiology, Pathology, and Laboratory Medicine, Department of Physics and Astronomy, and International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada
These individuals were workshop organizers and are equal contributors to this work.
Search for more papers by this authorGeorge R. Wayne Moore
Department of Pathology and Laboratory Medicine, and International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada
Search for more papers by this authorRiley Bove
Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA
Search for more papers by this authorZhengxin Cai
Department of Radiology and Biomedical Imaging, PET Center, Yale University, New Haven, CT
Search for more papers by this authorJulien Cohen-Adad
NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal and Functional Neuroimaging Unit, CRIUGM, University of Montreal, Montreal, Quebec, Canada
Search for more papers by this authorDaniel M. Harrison
Department of Neurology, University of Maryland School of Medicine, Baltimore, MD
Search for more papers by this authorEric C. Klawiter
Massachusetts General Hospital, Harvard Medical School, Boston, MA
Search for more papers by this authorSarah A. Morrow
Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada
Search for more papers by this authorGülin Öz
Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN
Search for more papers by this authorWilliam D. Rooney
Advanced Imaging Research Center, Departments of Biomedical Engineering, Neurology, and Behavioral Neuroscience, Oregon Health & Science University, Portland, OR
Search for more papers by this authorSeth A. Smith
Radiology and Radiological Sciences and Vanderbilt University Imaging Institute, Vanderbilt University Medical Center, and Biomedical Engineering, Vanderbilt University, Nashville, TN
Search for more papers by this authorPeter A. Calabresi
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorRoland G. Henry
Departments of Neurology, Radiology and Biomedical Imaging, and the UC San Francisco & Berkeley Bioengineering Graduate Group, University of California San Francisco, San Francisco, CA
Search for more papers by this authorJiwon Oh
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD
Division of Neurology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
Search for more papers by this authorDaniel Ontaneda
Mellen Center for Multiple Sclerosis, Neurological Institute, Cleveland Clinic, Cleveland, OH
Search for more papers by this authorDaniel Pelletier
Department of Neurology, University of Southern California Keck School of Medicine, Los Angeles, CA
Search for more papers by this authorDaniel S. Reich
Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD
Search for more papers by this authorRussell T. Shinohara
Department of Biostatistics, Epidemiology, and Informatics, Penn Statistics in Imaging and Visualization Center, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorNancy L. Sicotte
Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA
Search for more papers by this authorNAIMS Cooperative
Neuroimaging Unit, Neuroimmunology Division, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN
Search for more papers by this authorCorresponding Author
Francesca Bagnato
Neuroimaging Unit, Neuroimmunology Division, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN
These individuals were workshop organizers and are equal contributors to this work.
Correspondence: Address correspondence to Francesca Bagnato, Neuroimaging Unit, Neuroimmunology Division, Department of Neurology, Vanderbilt University Medical Center, 2201 Children's Way, Suite 1222, Nashville, TN 37212. E-mail: [email protected].
Search for more papers by this authorSusan A. Gauthier
Judith Jaffe Multiple Sclerosis Center, Department of Neurology, Feil Family Brain and Mind Institute, and Department of Radiology, Weill Cornell Medicine, New York, NY
These individuals were workshop organizers and are equal contributors to this work.
Search for more papers by this authorCornelia Laule
Department of Radiology, Pathology, and Laboratory Medicine, Department of Physics and Astronomy, and International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada
These individuals were workshop organizers and are equal contributors to this work.
Search for more papers by this authorGeorge R. Wayne Moore
Department of Pathology and Laboratory Medicine, and International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada
Search for more papers by this authorRiley Bove
Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA
Search for more papers by this authorZhengxin Cai
Department of Radiology and Biomedical Imaging, PET Center, Yale University, New Haven, CT
Search for more papers by this authorJulien Cohen-Adad
NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal and Functional Neuroimaging Unit, CRIUGM, University of Montreal, Montreal, Quebec, Canada
Search for more papers by this authorDaniel M. Harrison
Department of Neurology, University of Maryland School of Medicine, Baltimore, MD
Search for more papers by this authorEric C. Klawiter
Massachusetts General Hospital, Harvard Medical School, Boston, MA
Search for more papers by this authorSarah A. Morrow
Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada
Search for more papers by this authorGülin Öz
Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN
Search for more papers by this authorWilliam D. Rooney
Advanced Imaging Research Center, Departments of Biomedical Engineering, Neurology, and Behavioral Neuroscience, Oregon Health & Science University, Portland, OR
Search for more papers by this authorSeth A. Smith
Radiology and Radiological Sciences and Vanderbilt University Imaging Institute, Vanderbilt University Medical Center, and Biomedical Engineering, Vanderbilt University, Nashville, TN
Search for more papers by this authorPeter A. Calabresi
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorRoland G. Henry
Departments of Neurology, Radiology and Biomedical Imaging, and the UC San Francisco & Berkeley Bioengineering Graduate Group, University of California San Francisco, San Francisco, CA
Search for more papers by this authorJiwon Oh
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD
Division of Neurology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
Search for more papers by this authorDaniel Ontaneda
Mellen Center for Multiple Sclerosis, Neurological Institute, Cleveland Clinic, Cleveland, OH
Search for more papers by this authorDaniel Pelletier
Department of Neurology, University of Southern California Keck School of Medicine, Los Angeles, CA
Search for more papers by this authorDaniel S. Reich
Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD
Search for more papers by this authorRussell T. Shinohara
Department of Biostatistics, Epidemiology, and Informatics, Penn Statistics in Imaging and Visualization Center, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorNancy L. Sicotte
Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA
Search for more papers by this authorNAIMS Cooperative
Neuroimaging Unit, Neuroimmunology Division, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN
Search for more papers by this authorWe thank Amalie Chen from the Medical School at Vanderbilt University (currently Resident Physician, PGY-1 Departments of Internal Medicine and Neurology, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School) for her assistance in organizing the references and Dr. Karina Ciccone (Neuroimaging Unit, Neuroimmunology Division, Department of Neurology, Vanderbilt University Medical Center) for assistance with editorial changes during the revisions of the manuscript.
A full list of members of the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative at the time of the workshop is provided in the acknowledgment and disclosure section.
Dr. Bagnato serves in the Editorial Board of Journal of Neuroimaging, served on advisory boards for EMD Serono, acted as site PI for multi-center trial funded by Novartis, acts as site PI for a multi-center trial funded by EMD Serono, serves as consultant for Novartis. Dr. Bagnato receives funds from NIH: RO1 NS109114-01; NMSS: PP-1801-29686 and RG 1807-31051; and Biogen Idec. Dr. Gauthier serves in the Editorial Board of Journal of Neuroimaging and served as a consultant for Celgene. Dr. Gauthier receives funds from NIH: RO1 NS104283, RO1 NS105144, and R01 NS090464. Dr. Laule serves in the Editorial Board of Journal of Neuroimaging. Dr. Laule receives funds from the MS Society of Canada and the Natural Sciences and Engineering Research Council of Canada. Dr. Moore has received a grant-in-aid of research from Berlex Canada and a teaching honorarium from Teva, and served as a consultant to Schering. Dr. Moore receives funds from the MS Society of Canada: EGID 3248. Dr. Bove served as a consultant for EMD-Serono, Novartis, Roche Genentech, and Sanofi-Genzyme. Dr. Bove receives funds from NMSS CA TA 3062-A-3; California Institute to Advance Precision Medicine and Hilton Foundation Grant 16850. Dr. Cai has no conflicts to declare. Dr. Cai receives funds from NIH: K01 EB023312 and R01 AG058773. Dr. Cohen-Adad has no conflicts to declare. Dr. Cohen-Adad receives funds from the Canada Research Chair in Quantitative Magnetic Resonance Imaging: 950–230815; the Canadian Institute of Health Research: CIHR FDN-143263; the Canada Foundation for Innovation (32454, 34824); the Fonds de Recherche du Québec: Santé 28826; the Fonds de Recherche du Québec - Nature et Technologies: 2015-PR-182754; Natural Sciences and Engineering Research Council of Canada: RGPIN-2019-07244; Canada First Research Excellence Fund IVADO and TransMedTech; Quebec BioImaging Network: 5886, 35450. Dr. Harrison received consulting fees from EMD-Serono, Genzyme, Biogen, and Genentech. Dr. Harrison receives funds from NIH: 1K23NS072366-01A1 and 1R01NS104403-01, NMSS: PP-1804-30760, EMD Serono, and Roche Genentech. Dr. Klawiter receives consulting fees from Alexion, Biogen, EMD Serono, and Genentech. Dr. Klawiter receives funds from NIH K23NS078044, Abbvie, Biogen, EMD Serono, Genzyme, and Roche Genentech. Dr. Morrow served on advisory boards for Biogen Idec, EMD Serono, Genzyme Canada, Novartis, and Roche. Dr. Morrow received Investigator Initiated Grant Funds from Biogen Idec, Novartis, and Roche, and has acted as site PI for multi-center trials funded by Novartis, Genzyme, Roche, and AbbVie. Dr. Oz has no conflicts to declare. Dr. Oz receives funds from NIH: R01 NS080816 and P41 EB015894; the Institutional Center Cores for Advanced Neuroimaging: P30 NS076408. Dr. Rooney has no conflicts to declare. Dr. Rooney receives funds from the NIH: R01-EB007258 and R01NS40801; NMSS: RG 3168A1; C.N. Hilton Foundation MS Innovation Fund 20140260. Dr. Smith serves in the Board of Trustees for the Southeast NMSS. Dr. Smith receives funds from NIH: R01NS104149 and R01NS109114-01; NMSS: RG 1501–02840; C.N. Hilton Foundation MS Innovation Fund 17237; Novartis IIRP-1456. Dr. Calabresi received personal compensation for serving on scientific advisory boards from Disarm Therapeutics and Biogen Idec. Dr. Calabresi receives funds from NIH: R01NS082347, R37NS041435, and the NMSS. He is PI on grants from Biogen and Annexon to JHU. Dr. Oh serves on the Editorial Board of J Neuroimaging and receives funding from the MS Society of Canada, NMSS, Brain Canada, Biogen-Idec, Roche, and Sanofi-Genzyme. Dr. Oh has received personal compensation for consulting for Biogen-Idec, Celgene, Novartis, Sanofi-Genzyme, Roche, and EMD-Serono. Dr. Ontaneda received consulting fees from Biogen Idec, Genentech/Roche, Genzyme, Novartis, and Merck. Dr. Ontaneda has received research support from the NIH (R01NS091683 and R21NS106522), Patient Centered Outcomes Research Institute (PCORI MS-1610-37047) and the Department of Defense DOD (W81XWH-16-1-0446), the Race to Erase MS Foundation, Genentech, Genzyme, and Novartis. Dr. Pelletier received consulting fees from Alexion, Biogen, Genzyme, Novartis, and Roche. Dr. Reich received research funds via a Cooperative Research and Development Agreement with Vertex Pharmaceuticals, not connected to this paper. Dr. Reich is funded by the Intramural Research Program of NINDS. Dr. Shinohara has received consulting income from Genentech/Roche and compensation for editorial/reviewing duties from Research Square and the American Medical Association. Dr. Shinohara receives funds from NIH: R01 NS085211, R01 MH112847 and R01 NS060910) and the NMSS: RG-1707-28586 and PP-1901-33080. Dr. Sicotte has no conflicts to declare. Dr. Sicotte receives funds from the NMSS: RG1507-05418, PCORI: MS-1610-37115 and the Race to Erase MS: CAVS in Early MS.
The content is solely the responsibility of the authors and does not necessarily represent the official views of any of the funding agencies.
Members of the NAIMS at the time of the workshop and not listed as authors in the manuscript include: Drs. Brenda Banwell (Children's Hospital of Pennsylvania), Amit Bar-Or (University of Pennsylvania), Alex Brandt (University of California at Irvine), Phil De Jager (Columbia University), Leorah Freeman (University of Texas at Houston), Rohit Bakshi and Charles Guttmann (Brigham and Women's Hospital), Roland Henry (University of California San Francisco), Matilde Inglese (Icahn School of Medicine at Mount Sinai), Caterina Mainero (Massachusetts General Hospital), Naila Makhani (Yale University), Ravi Menon (Western University), Robert Naismith, (Washington University), Sridar Narayanan (McGill University), Bart Rympa (University of Texas South Western), Andrew Solomon (University of Vermont), Anthony Traboulsee (University of British Columbia), Alan Wilman (University of Alberta), Yunyan Zhang (University of Calgary), Robert Zivadinov (Buffalo Neuroimaging Analysis Center, State University of New York), Zongqi Xia (University of Pittsburgh).
ABSTRACT
Clinicians involved with different aspects of the care of persons with multiple sclerosis (MS) and scientists with expertise on clinical and imaging techniques convened in Dallas, TX, USA on February 27, 2019 at a North American Imaging in Multiple Sclerosis Cooperative workshop meeting. The aim of the workshop was to discuss cardinal pathobiological mechanisms implicated in the progression of MS and novel imaging techniques, beyond brain atrophy, to unravel these pathologies. Indeed, although brain volume assessment demonstrates changes linked to disease progression, identifying the biological mechanisms leading up to that volume loss are key for understanding disease mechanisms. To this end, the workshop focused on the application of advanced magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging techniques to assess and measure disease progression in both the brain and the spinal cord. Clinical translation of quantitative MRI was recognized as of vital importance, although the need to maintain a relatively short acquisition time mandated by most radiology departments remains the major obstacle toward this effort. Regarding PET, the panel agreed upon its utility to identify ongoing pathological processes. However, due to costs, required expertise, and the use of ionizing radiation, PET was not considered to be a viable option for ongoing care of persons with MS. Collaborative efforts fostering robust study designs and imaging technique standardization across scanners and centers are needed to unravel disease mechanisms leading to progression and discovering medications halting neurodegeneration and/or promoting repair.
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