Review

. 2019 Mar 12;92(11):519-533.

doi: 10.1212/WNL.0000000000007099. Epub 2019 Feb 20.

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

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, Affiliations

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.

PMID: 30787160
PMCID: PMC6511106
DOI: 10.1212/WNL.0000000000007099

Review

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

Jiwon Oh et al. Neurology. 2019.

. 2019 Mar 12;92(11):519-533.

doi: 10.1212/WNL.0000000000007099. Epub 2019 Feb 20.

Authors

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.

PMID: 30787160
PMCID: PMC6511106
DOI: 10.1212/WNL.0000000000007099

Erratum in

Imaging outcome measures of neuroprotection and repair in MS: A consensus statement from NAIMS.
[No authors listed] [No authors listed] Neurology. 2019 Jul 2;93(1):46. doi: 10.1212/WNL.0000000000007525. Neurology. 2019. PMID: 31262994 Free PMC article. No abstract available.

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.

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Figures

**Figure 1. Dynamic changes in magnetization transfer ratio (MTR) in an acute multiple sclerosis lesion: Potential utility in assessing novel therapeutics**
GM = gray matter; WM = white matter. Published with permission from Robert Brown.

**Figure 2. Theoretical basis of diffusion imaging**
(A) Water diffusion along intact axonal fiber tracts in intact brain tissue. (B) Dispersed water diffusion in brain tissue with demyelination and axonal injury. The arrows indicate the primary, second, and third eigenvectors of the diffusion tensor. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography © 2004–2018. All Rights Reserved.

**Figure 3. Susceptibility-weighted imaging**
Persistent phase rims in a gadolinium-enhancing lesion in a patient with secondary progressive multiple sclerosis. Postcontrast T1-weighted images demonstrate gadolinium enhancement evolution from centrifugal to centripetal. A hypointense rim can be visualized on noncontrast phase images when the lesion enhances centripetally, and is persistent after enhancement resolution (months 3, 6, 12, 18) and on T2* weighted images (months 6, 12, 18). MPRAGE = magnetization-prepared rapid gradient echo. Reproduced with permission from Absinta M, Sati P, Schindler M, et al. Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions. J Clin Invest 2016;126:2597–2609.

**Figure 4. Quantitative spinal cord MRI measures**
(A, B) Automated segmentation of spinal cord cross-sectional area. (C) Color-coded diffusion tensor imaging map (derived from fractional anisotropy and the principal eigenvector) demonstrates spinal cord fibers running along the rostrocaudal axis (blue). Reproduced with permission from Oh J, Sotirchos ES, Saidha S, et al. Relationships between quantitative spinal cord MRI and retinal layers in multiple sclerosis. Neurology 2015;84:720–728.

See this image and copyright information in PMC

References

1. Barkhof F, Calabresi PA, Miller DH, Reingold SC. Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol 2009;5:256–266. - PubMed
1. Oh J, Bakshi R, Calabresi PA, et al. . The NAIMS cooperative pilot project: design, implementation and future directions. Mult Scler 2017;24:1770–1772. - PMC - PubMed
1. Mahad DH, Trapp BD, Lassmann H. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol 2015;14:183–193. - PubMed
1. Vollmer T, Signorovitch J, Huynh L, et al. . The natural history of brain volume loss among patients with multiple sclerosis: a systematic literature review and meta-analysis. J Neurol Sci 2015;357:8–18. - PubMed
1. Franklin RJ, ffrench-Constant C, Edgar JM, Smith KJ. Neuroprotection and repair in multiple sclerosis. Nat Rev Neurol 2012;8:624–634. - PubMed

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Erratum in

Abstract

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical