Imaging outcome measures of neuroprotection and repair in MS: A consensus statement from NAIMS

Jiwon Oh; Daniel Ontaneda; Christina Azevedo; Eric C Klawiter; Martina Absinta; Douglas L Arnold; Rohit Bakshi; Peter A Calabresi; Ciprian Crainiceanu; Blake Dewey; Leorah Freeman; Susan Gauthier; Roland Henry; Mathilde Inglese; Shannon Kolind; David K B Li; Caterina Mainero; Ravi S Menon; Govind Nair; Sridar Narayanan; Flavia Nelson; Daniel Pelletier; Alexander Rauscher; William Rooney; Pascal Sati; Daniel Schwartz; Russell T Shinohara; Ian Tagge; Anthony Traboulsee; Yi Wang; Youngjin Yoo; Tarek Yousry; Yunyan Zhang; Zivadinov Robert; Nancy L Sicotte; Daniel S Reich; North American Imaging in Multiple Sclerosis Cooperative

doi:10.1212/WNL.0000000000007099

Imaging outcome measures of neuroprotection and repair in MS: A consensus statement from NAIMS

Neurology. 2019 Mar 12;92(11):519-533. doi: 10.1212/WNL.0000000000007099. Epub 2019 Feb 20.

Authors

Jiwon Oh¹, Daniel Ontaneda², Christina Azevedo², Eric C Klawiter², Martina Absinta², Douglas L Arnold², Rohit Bakshi², Peter A Calabresi², Ciprian Crainiceanu², Blake Dewey², Leorah Freeman², Susan Gauthier², Roland Henry², Mathilde Inglese², Shannon Kolind², David K B Li², Caterina Mainero², Ravi S Menon², Govind Nair², Sridar Narayanan², Flavia Nelson², Daniel Pelletier², Alexander Rauscher², William Rooney², Pascal Sati², Daniel Schwartz², Russell T Shinohara², Ian Tagge², Anthony Traboulsee², Yi Wang², Youngjin Yoo², Tarek Yousry², Yunyan Zhang², Zivadinov Robert², Nancy L Sicotte², Daniel S Reich²; North American Imaging in Multiple Sclerosis Cooperative

Collaborators

North American Imaging in Multiple Sclerosis Cooperative:
Jiwon Oh, Daniel Ontaneda, Christina Azevedo, Eric C Klawiter, Martina Absinta Douglas L Arnold, Rohit Bakshi, Peter A Calabresi, Ciprian Crainiceanu, Blake Dewey Leorah Freeman, Susan Gauthier, Roland Henry, Mathilde Inglese, Shannon Kolind, David K B Li, Caterina Mainero, Ravi S Menon, Govind Nair, Sridar Narayanan, Flavia Nelson, Daniel Pelletier, Alexander Rauscher, William Rooney, Pascal Sati, Daniel Schwartz, Russell T Shinohara, Ian Tagge, Anthony Traboulsee, Yi Wang, Youngjin Yoo, Tarek Yousry, Yunyan Zhang, Zivadinov Robert, Nancy L Sicotte, Daniel S Reich

Affiliations

¹ From the Division of Neurology (J.O.), St. Michael's Hospital, University of Toronto, Canada; Department of Neurology (J.O., P.A.C., B.D., D.S.R.), Johns Hopkins University, Baltimore, MD; Mellen Center for Multiple Sclerosis (D.O.), Cleveland Clinic, OH; Department of Neurology (C.A., D.P.), University of Southern California, Los Angeles; Department of Neurology (E.C.K.), Massachusetts General Hospital, Harvard Medical School, Boston; Translational Neuroradiology Unit (M.A., G.N., P.S., D.S.R.), National Institute of Neurological Disorders and Stroke, Bethesda, MD; Brain Imaging Centre (D.L.A., S.N.), Montreal Neurological Institute, McGill University, Canada; Departments of Neurology (R.B.) and Radiology (R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Biostatistics (C.C.), Johns Hopkins School of Public Health, Baltimore, MD; Department of Neurology (L.F.), University of Texas Health Science Center at Houston; Department of Neurology (S.G., Y.W.), Weill Cornell Medical College, Cornell University, Ithaca, NY; Department of Neurology (R.H.), University of California at San Francisco; Department of Neurology (M.I., A.T.), Mount Sinai Hospital, New York, NY; Division of Neurology, Department of Medicine (S.K., D.K.B.L.), Department of Radiology (S.K., D.K.B.L., A.R.), Department of Physics and Astronomy (S.K., A.R., A.T., Y.Y.), MS/MRI Research Group (S.K., D.K.B.L., A.T., Y.Y.), MRI Research Centre (S.K., D.K.B.L., A.R.), and Department of Pediatrics (A.R.), University of British Columbia, Vancouver, Canada; A. A. Martinos Center for Biomedical Imaging (C.M.), Department of Radiology, Massachusetts General Hospital, Boston; Centre for Functional and Metabolic Mapping (R.S.M.), Robarts Research Institute, Western University, London, CA; Department of Neurology (F.N.), University of Minnesota, Minneapolis; Advanced Imaging Research Center (W.R., D.S., I.T.), Oregon Health & Science University, Portland; Department of Biostatistics, Epidemiology, and Informatics (R.T.S.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Division of Neuroradiology and Neurophysics (T.Y.), University College London Institute of Neurology, UK; Department of Radiology (Y.Z.) and Department of Clinical Neurosciences and Hotchkiss Brain Institute (Y.Z.), University of Calgary, Canada; and Department of Neurology (N.L.S.), Cedars-Sinai Medical Center, Los Angeles, CA. ohjiw@smh.ca.
² From the Division of Neurology (J.O.), St. Michael's Hospital, University of Toronto, Canada; Department of Neurology (J.O., P.A.C., B.D., D.S.R.), Johns Hopkins University, Baltimore, MD; Mellen Center for Multiple Sclerosis (D.O.), Cleveland Clinic, OH; Department of Neurology (C.A., D.P.), University of Southern California, Los Angeles; Department of Neurology (E.C.K.), Massachusetts General Hospital, Harvard Medical School, Boston; Translational Neuroradiology Unit (M.A., G.N., P.S., D.S.R.), National Institute of Neurological Disorders and Stroke, Bethesda, MD; Brain Imaging Centre (D.L.A., S.N.), Montreal Neurological Institute, McGill University, Canada; Departments of Neurology (R.B.) and Radiology (R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Biostatistics (C.C.), Johns Hopkins School of Public Health, Baltimore, MD; Department of Neurology (L.F.), University of Texas Health Science Center at Houston; Department of Neurology (S.G., Y.W.), Weill Cornell Medical College, Cornell University, Ithaca, NY; Department of Neurology (R.H.), University of California at San Francisco; Department of Neurology (M.I., A.T.), Mount Sinai Hospital, New York, NY; Division of Neurology, Department of Medicine (S.K., D.K.B.L.), Department of Radiology (S.K., D.K.B.L., A.R.), Department of Physics and Astronomy (S.K., A.R., A.T., Y.Y.), MS/MRI Research Group (S.K., D.K.B.L., A.T., Y.Y.), MRI Research Centre (S.K., D.K.B.L., A.R.), and Department of Pediatrics (A.R.), University of British Columbia, Vancouver, Canada; A. A. Martinos Center for Biomedical Imaging (C.M.), Department of Radiology, Massachusetts General Hospital, Boston; Centre for Functional and Metabolic Mapping (R.S.M.), Robarts Research Institute, Western University, London, CA; Department of Neurology (F.N.), University of Minnesota, Minneapolis; Advanced Imaging Research Center (W.R., D.S., I.T.), Oregon Health & Science University, Portland; Department of Biostatistics, Epidemiology, and Informatics (R.T.S.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Division of Neuroradiology and Neurophysics (T.Y.), University College London Institute of Neurology, UK; Department of Radiology (Y.Z.) and Department of Clinical Neurosciences and Hotchkiss Brain Institute (Y.Z.), University of Calgary, Canada; and Department of Neurology (N.L.S.), Cedars-Sinai Medical Center, Los Angeles, CA.

Abstract

Objective: To summarize current and emerging imaging techniques that can be used to assess neuroprotection and repair in multiple sclerosis (MS), and to provide a consensus opinion on the potential utility of each technique in clinical trial settings.

Methods: Clinicians and scientists with expertise in the use of MRI in MS convened in Toronto, Canada, in November 2016 at a North American Imaging in Multiple Sclerosis (NAIMS) Cooperative workshop meeting. The discussion was compiled into a manuscript and circulated to all NAIMS members in attendance. Edits and feedback were incorporated until all authors were in agreement.

Results: A wide spectrum of imaging techniques and analysis methods in the context of specific study designs were discussed, with a focus on the utility and limitations of applying each technique to assess neuroprotection and repair. Techniques were discussed under specific themes, and included conventional imaging, magnetization transfer ratio, diffusion tensor imaging, susceptibility-weighted imaging, imaging cortical lesions, magnetic resonance spectroscopy, PET, advanced diffusion imaging, sodium imaging, multimodal techniques, imaging of special regions, statistical considerations, and study design.

Conclusions: Imaging biomarkers of neuroprotection and repair are an unmet need in MS. There are a number of promising techniques with different strengths and limitations, and selection of a specific technique will depend on a number of factors, notably the question the trial seeks to answer. Ongoing collaborative efforts will enable further refinement and improved methods to image the effect of novel therapeutic agents that exert benefit in MS predominately through neuroprotective and reparative mechanisms.

Publication types

Consensus Development Conference
Research Support, Non-U.S. Gov't
Review

MeSH terms

Brain / diagnostic imaging*
Diffusion Tensor Imaging
Humans
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Multimodal Imaging
Multiple Sclerosis / diagnostic imaging*
Multiple Sclerosis / therapy
Nerve Regeneration*
Neuroprotection*
Outcome Assessment, Health Care
Positron-Emission Tomography
Spinal Cord / diagnostic imaging*

Grants and funding

R01 NS060910/NS/NINDS NIH HHS/United States