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 NarayananFlavia 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, Nancy L. Sicotte, Daniel S. Reich

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations

Abstract

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.MethodsClinicians 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.ResultsA 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.ConclusionsImaging 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.

Original languageEnglish (US)
Pages (from-to)519-533
Number of pages15
JournalNeurology
Volume92
Issue number11
DOIs
StatePublished - Mar 12 2019

Bibliographical note

Funding Information:
J. Oh has received research grant funding from the MS Society of Canada, National Multiple Sclerosis Society (NMSS), Brain Canada, Biogen-Idec, and Sanofi-Genzyme; and has received personal compensation for consulting or speaking from EMD Serono, Sanofi-Genzyme, Biogen-Idec, Novartis, and Roche. D. Ontaneda has received research grant funding from the NMSS, NIH, Patient-Centered Research Institute, Race to Erase MS Foundation, Genentech, and Genzyme; and has received personal compensation for consulting from Biogen Idec, Genentech/Roche, Genzyme, and Merck. C. Azevedo has received personal compensation for consulting from Genentech, Genzyme, and Guerbet. E. Klawiter has received research grant funding from Atlas5D, Biogen, EMD Serono, and Roche, as well as personal compensation for consulting from Acorda, Atlas5D, Biogen, EMD Serono, Genentech, and Shire. M. Absinta has received grant funding from the NMSS and the Conrad N. Hilton Foundation. D. Arnold has received research grant funding and/ or personal compensation for consulting from Acorda, Adelphi, Alkermes, Biogen, Celgene, Frequency Therapeutics, Genentech, Genzyme, Hoffman-La Roche, Immuene Tolerance Network, Immunotec, MedDay, EMD Serono, Novartis, Pfizer, Receptos, Roche, Sanofi-Aventis, Canadian Institutes of Health Research, MS Society of Canada, and International Progressive MS Alliance; and holds an equity interest in NeuroRx Research. R. Bakshi has received research grant funding from EMD Serono and Sanofi-Genzyme, as well as personal compensation for consulting from Bayer, EMD Serono, Genentech, Guerbet, Sanofi-Genzyme, and Shire. P. Calabresi has received research grant funding from Annexon, MedImmune, Biogen, Sanofi, and Novartis, as well as personal compensation for consulting from Biogen and Disarm Therapeutics. C. Crainiceanu, B. Dewey, and L. Freeman report no disclosures relevant to the manuscript. S. Gauthier has received research grant funding from Mallinckrodt, Genzyme, and Novartis. R. Henry has received research grant funding from Genentech, MedDay, and Sanofi-Genzyme; and has received personal compensation for consulting from Hoffman-La Roche, Novartis, MedDay, AbbVie, and Questcor, as well as educational support from Teva and Genzyme. M. Inglese has received research grants from NIH, NMSS, DOD, and Teva Neuroscience. S. Kolind has received research grant funding from Hoffmann-La Roche and Sanofi-Genzyme. D. Li has received research funding from the Canadian Institute of Health Research and Multiple Sclerosis Society of Canada and has received consulting fees from Biogen-Idec, EMD Serono, Genzyme, Novartis, Nuron Biotech, Opexa, and Vertex Pharmaceuticals C. Mainero reports no disclosures relevant to the manuscript. R. Menon has received research grant funding from the Canadian Institutes of Health Research Foundation, Natural Science and Engineering Research Council of Canada, Brain Canada, and Siemens Healthineers; and sold a patent to Siemens Healthcare. G. Nair and S. Narayanan report no disclosures relevant to the manuscript. F. Nelson has received research grant funding from Alkermes, Novartis, and the NMSS, as well as personal compensation for speaking or consulting from Acorda, Bayer, Consortium of Multiple Sclerosis Centers, Genentech, Novartis, Sanofi-Genzyme, and Teva. D. Pelletier has served on scientific advisory boards for Biogen, EMD Serono, Genzyme/Sanofi Aventis, Hoffman-La Roche, and Novartis; has received research support for Biogen, Genzyme, Hoffman-La Roche, and the National Institute of Neurologic Disorders and Stroke of the NIH; and has received honoraria for providing consulting services at scientific advisory board meetings from Biogen, EMD Serono, Genzyme/Sanofi Aventis, Hoffman-La Roche, and Novartis. A. Rauscher has received personal compensation for speaking from Philips Medical and served on a scientific advisory board for Hoffmann-La Roche. W. Rooney has received salary support from the NIH, Conrad N. Hilton Foundation, Paul G. Allen Family Foundation, and Department of Defense, as well as personal compensation for consulting from Biogen and Teva. P. Sati and D. Schwartz report no disclosures relevant to the manuscript. R. Shinohara has received personal compensation for consulting and has served on a scientific advisory board for Genentech/ Roche. I. Tagge reports no disclosures relevant to the manuscript. A. Traboulsee has received research grant funding from Chugai, Roche, Novartis, Genzyme, and Biogen, as well as personal compensation for consulting or speaking from Genzyme, Roche, Teva, Biogen, and EMD Serono. Y. Wang owns equity in Medimagemetric LLC. Y. Yoo has received educational grant funding and support to attend conferences from the MS Society of Canada. T. Yousry has received research grant funding from the Medical Research Council, MS Society of Great Britain and Northern Ireland, Stroke Association, British Heart Foundation, Wellcome Trust, GlaxoSmithKline, Biogen Idec, Novartis, Merck, and MS Society of Australia; and has received personal compensation for consulting from Biogen Idec and Ixico Technologies Ltd., as well as travel support from the European Society of Radiology and Hikma. Y. Zhang has received research grant funding from the MS Society of Canada, Natural Sciences and Engineering Council of Canada, and Alberta Innovates. N. Sicotte has received research grant funding from the NMSS, Guthy-Jackson Charitable Foundation, and Patient-Centered Outcomes Research Institute. D. Reich has received personal compensation and/or nonfinancial support for speaking or consulting from Leventhal & Puga, LLC and At the Limits; and has a patent system and method of automatically detecting tissue abnormalities (US Patent 9607392) issued, and a patent method of analyzing multi-sequence MRI data for analyzing brain abnormalities in a subject (US20150045651A1) pending. Go to Neurology.org/N for full disclosures.

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