MRI biomarkers of disease progression and conversion to secondary-progressive multiple sclerosis

ABSTRACT

Introduction

Conventional imaging measures remain a key clinical tool for the diagnosis multiple sclerosis (MS) and monitoring of patients. However, most measures used in the clinic show unsatisfactory performance in predicting disease progression and conversion to secondary progressive MS.

Areas covered

Sophisticated imaging techniques have facilitated the identification of imaging biomarkers associated with disease progression, such as global and regional brain volume measures, and with conversion to secondary progressive MS, such as leptomeningeal contrast enhancement and chronic inflammation. The relevance of emerging imaging approaches partially overcoming intrinsic limitations of traditional techniques is also discussed.

Expert opinion

Imaging biomarkers capable of detecting tissue damage early on in the disease, with the potential to be applied in multicenter trials and at an individual level in clinical settings, are strongly needed. Several measures have been proposed, which exploit advanced imaging acquisitions and/or incorporate sophisticated post-processing, can quantify irreversible tissue damage. The progressively wider use of high-strength field MRI and the development of more advanced imaging techniques will help capture the missing pieces of the MS puzzle. The ability to more reliably identify those at risk for disability progression will allow for earlier intervention with the aim to favorably alter the disease course.

KEYWORDS:

• Biomarkers
• disability
• disease progression
• imaging
• multiple sclerosis
• MRI
• secondary progressive MS

Article highlights

• Most imaging measures used in the clinic show unsatisfactory performance in predicting disease progression and conversion to secondary progressive multiple sclerosis.

• Advanced imaging techniques allow for the in vivo assessment of underlying pathology that is more strongly associated with disease progression in multiple sclerosis.

• Novel post-processing algorithms allow for the assessment of existing datasets to further overall understanding of multiple sclerosis pathology.

• The field of multiple sclerosis research will continue to advance with the addition of emerging applications, including positron emission tomography, optical coherence tomography, and novel contrast agents.

• The potential to identify patients at increased risk of disease progression and conversion to secondary progressive multiple sclerosis will allow for earlier intervention to favorably alter the disease course.

Declaration of interest

R Zivadinov has received personal compensation from EMD Serono, Genzyme-Sanofi, Novartis, Celgene for speaking and consultant fees. He received financial support for research activities from Genzyme-Sanofi, Celgene, Novartis, Mapi Pharma, V-WAVE Medical and Protembis. MG Dwyer has received consultant fees from Claret Medical and EMD Serono and research grant support from Novartis. B Weinstock-Guttman received honoraria as a speaker and as a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme, Sanofi, Novartis, and Acorda. She received financial support for research activities from Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme, Sanofi, Novartis, and Acorda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health, under award Number UL1TR001412. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.