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Review
, 92 (11), 519-533

Imaging Outcome Measures of Neuroprotection and Repair in MS: A Consensus Statement From NAIMS

Collaborators, Affiliations
Review

Imaging Outcome Measures of Neuroprotection and Repair in MS: A Consensus Statement From NAIMS

Jiwon Oh et al. Neurology.

Erratum in

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.

Figures

Figure 1
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
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
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
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.

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